oxalates and Kidney-Failure--Chronic

Primary hyperoxalurias are a devastating family of diseases leading to multisystem oxalate deposition, nephrolithiasis, nephrocalcinosis and end-stage renal disease. Traditional treatment paradigms are limited to conservative management, dialysis and combined transplantation of the kidney and liver, of which the liver is the primary source of oxalate production. However, transplantation is associated with many potential complications, including operative risks, graft rejection, post-transplant organ failure, as well as lifelong immunosuppressive medications and their adverse effects. New therapeutics being developed for primary hyperoxalurias take advantage of biochemical knowledge about oxalate synthesis and metabolism, and seek to specifically target these pathways with the goal of decreasing the accumulation and deposition of oxalate in the body.

Topics: Female; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Oxalates

The primary hyperoxalurias (PHs) are inborn errors of glyoxylate metabolism characterized by endogenous oxalate overproduction in the liver, and thus elevated urinary oxalate excretion. The urinary calcium-oxalate (CaOx) supersaturation and the continuous renal accumulation of insoluble CaOx crystals yield a progressive decline in renal function that often ends with renal failure. In PH Type 1 (AGXT mutated), the most frequent and severe condition, patients typically progress to end-stage renal disease (ESRD); in PH Type 2 (GRHPR mutated), 20% of patients develop ESRD, while only one patient with PH Type 3 (HOGA1 mutated) has been reported with ESRD so far. Patients with ESRD undergo frequent maintenance (haemo)dialysis treatment, and finally must receive a combined liver-kidney transplantation as the only curative treatment option available in PH Type 1. In experimental models using oxalate-enriched chow, CaOx crystals were bound to renal tubular cells, promoting a pro-inflammatory environment that led to fibrogenesis in the renal parenchyma by activation of a NACHT, LRR and PYD domains-containing protein 3 (NALP3)-dependent inflammasome in renal dendritic cells and macrophages. Chronic fibrogenesis progressively impaired renal function. Targeting the inflammatory response has recently been suggested as a therapeutic strategy to treat not only oxalate-induced crystalline nephropathies, but also those characterized by accumulation of cystine and urate in other organs. Herein, we summarize the pathogenesis of PH, revising the current knowledge of the CaOx-mediated inflammatory response in animal models of endogenous oxalate overproduction. Furthermore, we highlight the possibility of modifying the NLRP3-dependent inflammasome as a new and complementary therapeutic strategy to treat this severe and devastating kidney disease.

Topics: Adolescent; Adult; Animals; Calcium Oxalate; Child; Child, Preschool; Disease Models, Animal; Humans; Hyperoxaluria, Primary; Infant; Inflammasomes; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Macrophages; Mice; Nephritis; NLR Family, Pyrin Domain-Containing 3 Protein; Oxalates; Renal Dialysis; Renal Insufficiency; RNA Interference; Uric Acid; Young Adult

Type 1 primary hyperoxaluria is a genetic disorder caused by deficiency of the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. This enzyme deficiency leads to excess oxalate production and deposition of calcium oxalate salts, resulting in kidney failure and systemic oxalosis. Aside from combined liver/kidney transplantation, no curative treatment exists. Various strategies for optimizing dialysis treatment have been evaluated, but neither conventional hemodialysis nor peritoneal dialysis can keep pace with oxalate production in this patient population. In this report, we describe a patient with end-stage renal disease from type 1 primary hyperoxaluria managed with nocturnal home hemodialysis. Performing hemodialysis 8-10 hours each night with blood flow of 350 mL/min and total dialysate volume of 60 L, she has maintained pre- and postdialysis serum oxalate levels at or below the level of supersaturation. We also review published literature regarding oxalate removal in various modalities of dialysis in patients with type 1 primary hyperoxaluria. In our patient, nocturnal hemodialysis has controlled serum oxalate levels better than conventional hemodialysis therapies. Home nocturnal hemodialysis should be considered an option for management of patients with end-stage renal disease from type 1 hyperoxaluria who are awaiting transplantation.

Topics: Adult; Amino Acid Substitution; Arginine; Circadian Rhythm; Combined Modality Therapy; DNA Mutational Analysis; Exons; Female; Glycine; Hemodialysis, Home; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Oxalates; Pyridoxine; Transaminases

In addition to monosodium urate, calcium pyrophosphate dihydrate, and apatite crystals, oxalate crystals are less often found in synovial fluids in association with acute or chronic arthritis. Oxalate crystal deposition disease is seen in patients with primary hyperoxaluria types 1 and 2 (PH1 and 2) and in patients with end-stage renal disease managed with long-term dialysis. Oxalate crystal deposits are found mainly in kidneys, bone, skin, and vessels, and less often inside the joints. Musculoskeletal and systemic manifestations of oxalate crystal deposition disease may be confused with those observed with the other most common types of crystal deposition diseases. Clinical and radiographic features include calcium oxalate osteopathy, acute and chronic arthropathy with chondrocalcinosis, synovial calcification, and miliary skin calcium oxalate deposits and vascular calcifications that affect mainly the hands and feet. Systemic life-threatening cardiovascular, neurologic, and hematologic manifestations are rare. Genomic DNA studies have identified those genetic defects of PH1 and PH2 that allow a precise early diagnosis. Kidney transplantation has poor outcome as a result of graft oxalosis. Combined liver and kidney transplantation is the treatment of choice in patients with PH1 and advanced renal failure. Pre-emptive isolated liver transplantation is the preferred treatment in patients who develop the disease during infancy with progressive manifestations of oxalosis. These novel findings in the understanding of the molecular and enzymatic aspects of primary hyperoxalurias have provided a more rational basis for the management and prevention of oxalate crystal deposition disease. This information may lead to a better understanding and effective management of other common calcium-containing crystal deposition diseases.

Topics: Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Oxalates

Normally, absorption of oxalate from dietary sources can occur in all segments of the intestinal tract. However, alterations in both the magnitude and direction of oxalate fluxes across the intestine can occur in disease states. In enteric hyperoxaluria, enhanced absorption of oxalate by the large intestine is caused by increased permeability of a shunt conductance induced by malabsorbed bile salts and fatty acids. In this condition, the contribution of a paracellular passive flux of oxalate moving along its electrochemical gradient will predominate when intraluminal concentrations of free oxalate are high. In contrast, in chronic renal failure, secretion of oxalate can occur across both small and large intestine thereby facilitating extrarenal elimination with subsequent degradation by mucosal substrate-specific microorganisms. Clearly, in recent studies of oxalate transport, the intestine has emerged with an integral role in mass balance of oxalate in health and disease.

Topics: Animals; Humans; Hyperoxaluria; Intestinal Absorption; Kidney Failure, Chronic; Oxalates

Topics: Adult; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Male; Muscles; Muscular Atrophy; Nerve Degeneration; Nerve Fibers, Myelinated; Neuromuscular Diseases; Oxalates; Polyneuropathies; Sural Nerve

Topics: Humans; Joint Diseases; Kidney Failure, Chronic; Oxalates; Renal Dialysis

Topics: Humans; Kidney; Kidney Failure, Chronic; Oxalates

Acquired cystic disease (ACD) is a recently described phenomenon occurring in the native kidneys of patients treated with long-term dialysis. Renal cell carcinoma is being diagnosed with increasing frequency in patients with chronic renal failure. In most, but not all, instances the cancers develop in association with ACD. Careful microscopic examination of end-stage kidneys undergoing dialysis discloses cysts lined with hyperplastic cells. Papillary hyperplasia of cyst epithelium is recorded in virtually every detailed pathology report of tumors arising in ACD and is the likely pathogenetic basis for the development of renal tumors in cystic kidneys undergoing dialysis. The pathology of ACD and its related neoplasms is reviewed. An estimate is made of the incidence of ACD and renal cell carcinoma in patients receiving dialysis by tabulating data from studies published in medical journals. Acquired cystic disease is found in approximately 35% of patients treated by long-term hemodialysis. Renal cell carcinoma occurs in approximately 5.8% of cases of ACD. Most of the cancers are found incidentally at autopsy or by examination of kidneys from bilateral nephrectomies and are of little clinical significance, but occasional cases present aggressive neoplasms that metastasize and cause the deaths of patients.

Topics: Age Factors; Carcinoma, Renal Cell; Epithelium; Female; Humans; Hyperplasia; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Polycystic Kidney Diseases; Renal Dialysis; Time Factors

Topics: Ascorbic Acid; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Thiamine Deficiency; Vitamin B 6 Deficiency

Two cases of oxalosis in infancy are reported, the diagnosis and therapy are discussed and the world literature reviewed. Oxalosis in infancy is a rare condition, probably most frequently caused by a fulminant form of the autosomal recessive type I primary hyperoxaluria. It presents symptoms of renal failure in early infancy. This is progressive and usually causes death within three months after the onset of symptoms. The diagnosis can be suspected after simple procedures (abdominal roentgenogram, urinary tract ultrasonography) and confirmed by urine/plasma analysis and kidney biopsy/bone marrow aspiration. An exact diagnosis is important since it has consequences concerning genetic counseling and treatment. Dialysis and transplantation may be useful in secondary oxalosis, but until now they are hard to justify in infantile primary oxalosis. In primary hyperoxaluria (type I), pyridoxine therapy gives hopeful results before the onset of oxalosis, but unsatisfactory results after the onset of oxalosis.

Topics: Consanguinity; Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Kidney Failure, Chronic; Male; Metabolism, Inborn Errors; Oxalates; Pedigree; Pyridoxine; Ultrasonography

Topics: Adult; Chromatography; Colorimetry; Electrophoresis; Female; Fluorometry; Gastrointestinal Diseases; Humans; Infant; Intestinal Absorption; Kidney Failure, Chronic; Oxalates; Radioisotope Dilution Technique; Reference Standards; Tissue Distribution; Vitamin B 6 Deficiency

In primary hyperoxaluria Type 1 (PH1), endogenous oxalate overproduction significantly elevates urinary oxalate excretion, resulting in recurrent urolithiasis and/or progressive nephrocalcinosis and often early end-stage renal disease (ESRD). In ESRD, dialysis cannot sufficiently remove oxalate; plasma oxalate (Pox) increases markedly, inducing systemic oxalate deposition (oxalosis) and often death. Interventions to reduce Pox in PH1 subjects with ESRD could have significant clinical impact. This ongoing Phase II, open-label trial aimed to evaluate whether long-term Oxabact™ (Oxalobacter formigenes, OC5, OxThera Intellectual Property AB, Sweden) lowers Pox in PH1 ESRD subjects, ameliorating clinical outcome.. PH1 ESRD subjects on stable dialysis regimens were examined. Subjects were administered one OC5 capsule twice daily for up to 36 months or until transplantation. Total Pox values, cardiac function and safety were evaluated. Free Pox was evaluated in a comparative non-treated PH1 dialysis group using retrospective chart reviews and analyses.. Twelve subjects enrolled in an initial 6-week treatment phase. Following a washout of up to 4 weeks, eight subjects entered a continuation study; outcomes after 24 months of treatment are presented. After 24 months, all subjects had reduced or non-elevated Pox compared with baseline. Cardiac function improved, then stabilized. No treatment-related serious adverse events were reported.. Compared with an untreated natural control cohort, 24 months OC5 administration was beneficial to PH1 ESRD subjects by substantially decreasing Pox concentrations, and improving or stabilizing cardiac function and clinical status, without increasing dialysis frequency. OC5 was safe and well-tolerated.

Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Oxalates; Oxalobacter formigenes; Renal Dialysis; Retrospective Studies

The clinical significance of accumulating toxic terminal metabolites such as oxalate in patients with kidney failure is not well understood.. To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of patients with kidney failure requiring chronic dialysis, we performed a. A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 patients died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular end point (cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Patients in the highest oxalate quartile (≥59.7 µM) had a 40% increased risk for cardiovascular events (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [95% CI], 1.08 to 1.81) and a 62% increased risk of sudden cardiac death (aHR, 1.62; 95% CI, 1.03 to 2.56), compared with those in the lowest quartile (≤29.6 µM). The associations remained when accounting for competing risks and with oxalate as a continuous variable.. Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in patients on dialysis. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in patients on dialysis.

Topics: Aged; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Factors

Primary hyperoxaluria (PH) is a rare genetic disease, in which high urinary oxalate (Uox) cause recurrent kidney stones and/or progressive nephrocalcinosis, often followed by early end-stage renal disease, as well as extremely high plasma oxalate, systemic oxalosis and premature death. Oxalobacter formigenes, an anaerobic oxalate degrading bacterium, naturally colonizes the colon of most humans. Orally administered O. formigenes (Oxabact) was found to significantly reduce urine and plasma oxalate. We aimed to evaluate its effect and safety in a randomized, double-blind, placebo-controlled multicenter study.. Oral Oxabact was given to PH patients (>5 years old, Uox > 1.0 mmol/1.73 m(2)/day, glomerular filtration rate (GFR) > 50 mL/min) at nine PH referral sites worldwide. Primary endpoint was the change from baseline in Uox (mmol/1.73 m(2)/day) after 24 weeks of treatment (>20% reduction).. Of the 43 subjects randomized, 42 patients received either placebo (23 subjects) or Oxabact (19 subjects). The change in Uox was <20% and not different between groups (P = 0.616). Ad hoc analysis was performed in 37 patients compliant with medication and urine processing. Change in Uox was -19% in subjects given Oxabact and -10% in placebo, (P = 0.288), but -21 and -7% with Uox expressed as molar creatinine ratio (Ox:Cr, mmol/mol, P = 0.06). Reduction of Ox:Cr was more obvious for patients with higher baseline values (>160 mmol/mol, Oxabact -28%, placebo -6%; P < 0.082). No serious adverse events were reported.. Oxabact was safe and well tolerated. However, as no significant change in Uox was seen, further studies to evaluate the efficacy of Oxabact treatment are needed.

Topics: Administration, Oral; Aged; Creatinine; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Calculi; Kidney Failure, Chronic; Male; Oxalates; Oxalobacter formigenes; Prognosis

Chronic hemodialysis (HD) patients manifest anemia and atherosclerosis with associated oxidative stress. We explored whether intravenous infusion of vitamin C (VC) and/or use of vitamin E (VE)-coated dialysis membrane could palliate HD-evoked oxidative stress. Eighty patients undergoing chronic HD were enrolled and randomly assigned into four groups: HD with intravenous VC (n=20), HD with VE-coated dialyzer (n=20), HD with both (n=20), and HD with neither (n=20). We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin/ferricyanide reductase (red blood cells (RBC)-MFR) activity, plasma methemoglobin, and pro-inflammatory cytokines in these patients. All patients showed marked increases (14-fold) in blood reactive oxygen species (ROS) after HD. The types of ROS were mostly hydrogen peroxide, and in lesser amounts, O2*- and HOCl. HD resulted in decreased plasma VC, total antioxidant status, and RBC-MFR activity and increased plasma and erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and methemoglobin. Intravenous VC significantly palliated HD-induced oxidative stress, plasma and RBC levels of PCOOH, and plasma methemoglobin levels and preserved RBC-MFR activity. The VE-coated dialyzer effectively prevented RBCs from oxidative stress, although it showed a partial effect on the reduction of total ROS activity in whole blood. In conclusion, intravenous VC plus a VE-coated dialyzer is effective in palliating HD-evoked oxidative stress, as indicated by hemolysis and lipid peroxidation, and by overexpression of proinflammation cytokines in HD patients. Using VE-coated dialyzer per se is, however, effective in reducing lipid peroxidation and oxidative damage to RBCs.

Topics: Antioxidants; Ascorbic Acid; Cytokines; Erythropoietin; Female; Hemolysis; Humans; Hydrogen Peroxide; Infusions, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Membranes, Artificial; Methemoglobin; NADH, NADPH Oxidoreductases; Oxalates; Oxidative Stress; Phosphatidylcholines; Reactive Oxygen Species; Renal Dialysis; Spectrophotometry, Atomic; Vitamin E

Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.

Topics: Administration, Oral; Adolescent; Adult; Capsules; Child; Child, Preschool; Chromatography, Gas; Creatinine; Feces; Female; Flame Ionization; Follow-Up Studies; Humans; Hyperoxaluria, Primary; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Oxalates; Oxalobacter formigenes; Time Factors; Treatment Outcome; Ultrasonography

To investigate if oral use of Sorbifer Durules (EGIS Pharmaceutical Ltd, Budapest, Hungary) (1 tablet/d) is adequate for the maintenance of serum iron and vitamin C in normal range during recombinant human erythropoietin treatment in hemodialyzed patients. One tablet of Sorbifer Durules contains 100 mg of Fe(2+) and 60 mg of vitamin C.. Short-term, open-label clinical trial.. Hemodialysis units.. Twenty-four adult patients with end-stage renal disease on hemodialysis.. Four-week treatment period of Sorbifer Durules, preceded and followed by iron and vitamin C washout periods.. Fasting predialysis serum samples were collected on days 0, 28, 56, and 84 to determine hematocrit, blood hemoglobin, serum iron, total iron-binding capacity, transferrin saturation, ferritin, vitamin C, and plasma oxalate.. Four-week treatment in hemodialyzed patients by Sorbifer Durules led to significant increase of hematocrit, blood hemoglobin, serum iron and vitamin C. This treatment did not influence the level of plasma oxalate.. Oral dose of one tablet of Sorbifer Durules per day is adequate for the maintenance of serum iron in normal range during recombinant human erythropoietin treatment in hemodialyzed patients. This treatment simultaneously prevented the development of serum vitamin C deficiency and did not lead to further increase of plasma oxalate in these patients.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Ascorbic Acid; Creatinine; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Iron; Iron Deficiencies; Iron, Dietary; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Recombinant Proteins; Renal Dialysis; Transferrin

Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7-18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12 +/- 11 months in CAPD and 31 +/- 23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/ min per 1.73 m2 in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 mumol/1.73 m2 surface area/week in CAPD versus 3,915 mumol/1.73 m2 per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 mumol/week. Plasma oxalate remained elevated in both procedures [28-84 mumol/l in CAPD (92/148 in PH) and 33-101 mumol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen.

Topics: Adolescent; Blood Urea Nitrogen; Child; Child, Preschool; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Oxalates; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

With declining kidney function and therefore increasing plasma oxalate, patients with primary hyperoxaluria type I (PHI) are at risk to systemically deposit calcium-oxalate crystals. This systemic oxalosis may occur even at early stages of chronic kidney failure (CKD) but is difficult to detect with non-invasive imaging procedures.. We tested if magnetic resonance imaging (MRI) is sensitive to detect oxalate deposition in bone. A 3 Tesla MRI of the left knee/tibial metaphysis was performed in 46 patients with PHI and in 12 healthy controls. In addition to the investigator's interpretation, signal intensities (SI) within a region of interest (ROI, transverse images below the level of the physis in the proximal tibial metaphysis) were measured pixelwise, and statistical parameters of their distribution were calculated. In addition, 52 parameters of texture analysis were evaluated. Plasma oxalate and CKD status were correlated to MRI findings. MRI was then implemented in routine practice.. Independent interpretation by investigators was consistent in most cases and clearly differentiated patients from controls. Statistically significant differences were seen between patients and controls (p < 0.05). No correlation/relation between the MRI parameters and CKD stages or Pox levels was found. However, MR imaging of oxalate osteopathy revealed changes attributed to clinical status which differed clearly to that in secondary hyperparathyroidism.. MRI is able to visually detect (early) oxalate osteopathy in PHI. It can be used for its monitoring and is distinguished from renal osteodystrophy. In the future, machine learning algorithms may aid in the objective assessment of oxalate deposition in bone. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Calcium Oxalate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Oxalates

Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Oxalates; Recurrence

Topics: Calcium; Chelating Agents; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Oxalates; Phosphates; Renal Dialysis; Sevelamer

A 19-year-old girl presented to the emergency department with a progressively painful purpuric lesion on the left dorsal foot, which had initially appeared 2 days prior. Three months earlier, she had been diagnosed with end-stage renal disease. Her medical history also included recurrent urolithiasis for the past 5 years and liver failure. Biopsy revealed oxalate crystals occluding vessels with secondary epidermal and dermal ischemia. Oxalate crystals were also visualized in the vessel walls and free in the subcutis. Genetic testing confirmed the diagnosis of primary hyperoxaluria type 1. She was treated with sodium thiosulfate, apixaban, pentoxifylline, wound care, and palliative care. At 4-month follow-up, the cutaneous manifestations of oxalosis were confined to only her feet, and she was undergoing evaluation for combined liver and kidney transplant. Cutaneous oxalosis because of primary hyperoxaluria should be considered in young patients presenting with purpuric lesions, recurrent urolithiasis, and early-onset renal failure.

Topics: Adult; Female; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Oxalates; Urolithiasis; Young Adult

Malnutrition and anorexia are common in children with chronic kidney disease (CKD) and gastrostomy tubes (GT) as well as nasogastric tubes (NGT) have been recommended to maximize nutritional support. The optimal requirement of vitamin C in children with CKD remains to be defined but oxalate is a breakdown product of vitamin C. Elevated vitamin C intake and bone oxalate were identified in two formula-fed dialyzed children with negative genetic testing for primary hyperoxaluria.. We evaluated the impact of nutritional support on serum ascorbic acid and plasma oxalate levels in 13 dialyzed infants and young children.. All patients were fed by GT or NGT since the first months of life; overall patients were receiving between 145 and 847% of the age-specific DRI for vitamin C. Mean serum ascorbic acid and plasma oxalate levels were elevated (244.7 ± 139.7 μM/L and 44.3 ± 23.1 μM/L, respectively), and values did not differ according to the degree of residual kidney function. Ascorbic acid levels did not correlate with oxalate levels (r = 0.44, p = 0.13).. Excessive vitamin C intake may contribute to oxalate accumulation in dialyzed children.

Topics: Ascorbic Acid; Child; Child, Preschool; Humans; Hyperoxaluria; Infant; Kidney Failure, Chronic; Oxalates; Renal Dialysis; Renal Insufficiency, Chronic; Vitamins

Topics: Adult; Female; Homozygote; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Middle Aged; Oxalates; Pyridoxine; Recovery of Function; Renal Dialysis; Renal Insufficiency, Chronic; Transaminases; Vitamin B Complex; Young Adult

Primary hyperoxaluria (PH) is a rare genetic disorder with autosomal recessive transmission, characterized by high endogenous production and markedly excessive urinary excretion of oxalate (Ox). It causes the accumulation of calcium oxide crystals in organs and tissues including bones, heart, arteries, skin and kidneys, where it may cause oxalo-calcic nephrolithiasis, nephrocalcinosis and chronic renal failure. Some forms are secondary to enteric diseases, drugs or dietetic substances, while three primitive forms, caused by various enzymatic defects, are currently known: PH1, PH2 and PH3. An early diagnosis, with the aid of biochemical and genetic investigations, helps prevent complications and establish a therapeutic strategy that often includes liver and liver-kidney transplantation, improving the prognosis of these patients. In this work we describe the clinical case of a patient with PH1 undergoing extracorporeal hemodialysis treatment and we report the latest research results that could change the life of patients with PH.

Topics: Calciphylaxis; Calcium Compounds; Female; Glyoxylates; Hemodiafiltration; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Nephrocalcinosis; Off-Label Use; Oxalates; Oxides; Renal Dialysis; Skin Diseases, Metabolic; Thiosulfates; Transaminases

Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver; Liver Transplantation; Oxalates

Primary hyperoxaluria is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage. Most patients with primary hyperoxaluria are diagnosed after clinical suspicion based on symptoms. Since some patients are detected by family screening following detection of an affected family member, we compared the clinical phenotype of these two groups. Patients with primary hyperoxaluria types 1, 2, and 3 enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria Registry were retrospectively analyzed following capture of clinical and laboratory results in the Registry. Among 495 patients with primary hyperoxaluria, 47 were detected by family screening. After excluding 150 patients with end stage kidney disease at diagnosis, 300 clinical suspicion and 45 family screening individuals remained. Compared to patients with clinical suspicion, those identified by family screening had significantly fewer stones at diagnosis (mean 1.2 vs. 3.6), although initial symptoms occurred at a similar age (median age 6.1 vs. 7.6 years). Urinary oxalate did not differ between these groups. The estimated glomerular filtration rate at diagnosis and its decline over time were similar for the two groups. Altogether, five of 45 in family screening and 67 of 300 of clinical suspicion individuals developed end stage kidney disease at last follow-up. Thus, patients with primary hyperoxaluria identified through family screening have significant disease despite no outward clinical suspicion at diagnosis. Since promising novel treatments are emerging, genetic screening of family members is warranted because they are at significant risk for disease progression.

Topics: Child; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Nephrocalcinosis; Oxalates; Retrospective Studies

We aim to describe the clinical and histological findings in patients with the finding of any tubular oxalate deposits in kidney biopsy specimens.. The prevalence, manifestation, and outcome of secondary oxalate nephropathy have not been extensively studied.. In this retrospective cohort study, we analyzed the clinical and histological findings in all patients with the finding of any tubular oxalate deposits in kidney biopsy specimens between July 1, 2017, and December 31, 2018, at Northwell Health Pathology Department (Manhasset, NY, USA).. The prevalence of oxalate deposition on a kidney biopsy was 4.07% (25/615), and in 88% of cases was a major finding. Prior to biopsy, oxalate was anticipated in only 1 case. The etiology of oxalosis was clarified retrospectively in 14 cases, most commonly due to GI surgery (n = 10) and increased oxalate intake (n = 4). In 11 cases, etiology remained unknown, although at least 3 cases were exposed to antibiotics associated with secondary oxalosis. There was no significant clinical/pathological or survival difference between known vs. unknown cause groups. The overall 3-month renal survival rate was 76.0 ± 8.5%. Multivariate Cox regression showed that creatinine at the time of biopsy (HR: 1.79, 95% CI: 0.71 - 4.51), background histological chronicity change (HR: 1.82, 95% CI: 0.70 - 4.72) and oxalate density (HR: 2.27, 95% CI: 0.49 - 10.55) are associated with end-stage kidney disease.. Oxalate deposition is common but rarely anticipated biopsy finding. Nephrologists need to consider surgical history and other secondary causes of oxalosis as causes of acute kidney injury and chronic kidney disease.

Topics: Aged; Biopsy; Crystallization; Female; Humans; Hyperoxaluria; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Retrospective Studies

Primary hyperoxalurias are rare diseases with endogenous overproduction of oxalate, thus leading to hyperoxaluria, hyperoxalemia, urolithiasis, and/or nephrocalcinosis and eventually early kidney failure. Plasma oxalate (POx) is an important diagnostic parameter in clinical studies on primary hyperoxaluria (PH). This is especially the case in kidney failure, where urinary parameters are no longer suitable. We aimed to evaluate whether POx would be an adequate endpoint for clinical studies in PH patients with stable kidney function. In addition, the correlation of POx to serum creatinine (SCr) and calculated glomerular filtration rate (eGFR) was examined.. We retrospectively analyzed follow-up of individual POx values over time, as well as POx correlation to SCr, eGFR, and vitamin B6 (VB6), a common therapeutic in PH1. Results from 187 blood samples taken between 2009 and 2017, during routine laboratory evaluations from 41 patients with PH1 who had neither undergone dialysis nor transplantation, were evaluated.. Negligibly low correlation coefficients (CCs) between POx vs. SCr (CC = -0.0950), POx vs. eGFR (CC = -0.1237), and POx vs. VB6 (CC = 0.1879) were found, with the exception of CKD stage 3a patients, who showed a positive correlation (CC of - 0.7329, POx vs eGFR). The intra-individual analysis of POx over time showed a high fluctuation of POx values.. We conclude that POx has a limited validity as a primary endpoint for clinical studies in PH1 patients with stable kidney function. In addition, it does not correlate to SCr and eGFR in this group of patients.

Topics: Adolescent; Adult; Biomarkers; Child; Child, Preschool; Clinical Trials as Topic; Creatinine; Endpoint Determination; Female; Glomerular Filtration Rate; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Retrospective Studies; Young Adult

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

Topics: Humans; Inonotus; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Risk Factors; Tomography, X-Ray Computed; Vascular Calcification

Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.. We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.. This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.

Topics: Acetates; Aged, 80 and over; Calcium Compounds; Carcinoma, Renal Cell; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Pancreatic Neoplasms; Pancrelipase; Protein Kinase Inhibitors; Pyrimidines; Renal Dialysis; Sulfonamides; Treatment Outcome

Oxalate kidney injury can manifest as oxalate nephropathy or nephrolithiasis and present as acute kidney injury or even as end-stage renal disease. There are several known causes for acute oxalate nephropathy; however, the combination of exocrine pancreatic insufficiency with overconsumption of vitamin C has not been described before. In this case, a man in his early 80s presented with anorexia and extreme fatigue for 1 week. He had a history of myalgic encephalomyelitis, also known as chronic fatigue syndrome, for which he took several supplements, including high doses of vitamin C. Furthermore, several years ago, he was diagnosed elsewhere with exocrine pancreatic insufficiency. On admission, acute kidney injury was diagnosed. The kidney biopsy showed oxalate nephropathy as the cause. We diagnosed acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency. Within 14 days, his kidney function got worse and he required renal replacement therapy.

Topics: Acute Disease; Acute Kidney Injury; Aged, 80 and over; Ascorbic Acid; Exocrine Pancreatic Insufficiency; Humans; Hyperoxaluria; Kidney; Kidney Failure, Chronic; Male; Oxalates; Renal Replacement Therapy

Oxalate nephropathy is an uncommon condition that causes acute kidney injury with the potential for progression to end-stage renal disease. Diagnosis is based on the kidney biopsy findings of abundant polarizable calcium oxalate crystals in the epithelium and lumen of renal tubules. We report a case of acute oxalate nephropathy in a 65-year-old woman, temporally associated with the consumption of an oxalate-rich green smoothie juice "cleanse" prepared from juicing oxalate-rich green leafy vegetables and fruits. Predisposing factors included a remote history of gastric bypass and recent prolonged antibiotic therapy. She had normal kidney function before using the cleanse and developed acute kidney injury that progressed to end-stage renal disease. Consumption of such juice cleanses increases oxalate absorption, causing hyperoxaluria and acute oxalate nephropathy in patients with predisposing risk factors. Given the increasing popularity of juice cleanses, it is important that both patients and physicians have greater awareness of the potential for acute oxalate nephropathy in susceptible individuals with risk factors such as chronic kidney disease, gastric bypass, and antibiotic use.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Disease Progression; Female; Fruit and Vegetable Juices; Gastric Bypass; Humans; Hyperoxaluria; Kidney; Kidney Failure, Chronic; Oxalates; Renal Dialysis; Risk Factors; Treatment Outcome

Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015.. On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 μmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 μmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function.. While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.

Topics: Child; Child, Preschool; Female; Humans; Hyperoxaluria, Primary; Infant; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Nephrectomy; Oxalates; Retrospective Studies; Treatment Outcome

Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD).. The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. After exclusion of patients not in steady state at the time of blood draw, 270 patients were available for study. Records were reviewed for clinical diagnoses to categorize patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls without USD undergoing clinical GFR testing.. In all 3 groups POx increased as eGFR fell. For any given eGFR, POx was highest in the PH group and lowest in the USD and control groups (p<0.0001). POx was also influenced by UOx excretion (reflecting total body oxalate burden, absorption from diet and endogenous production). Generalized estimating equations of POx vs eGFR revealed higher average POx levels in PH compared to EH,USD or control, and for EH compared to USD or control. GEE prediction models were created that use POx, UOx, age, and serum creatinine to estimate the probability of a PH diagnosis.. New models were developed to help interpret POx when considering PH in clinical practice even when it was not previously suspected and/or eGFR is reduced.

Topics: Adult; Calcium Oxalate; Female; Glomerular Filtration Rate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Diseases; Kidney Failure, Chronic; Male; Metabolic Diseases; Middle Aged; Oxalates; Urinary Calculi

Primary hyperoxaluria type 1 (PH1) is a rare liver enzymatic defect that causes overproduction of plasma oxalate. Accumulation of oxalate in the kidney and subsequent renal failure are fatal to PH1 patients often in pediatric age. Combined liver and kidney transplantation is the therapy of choice for end-stage renal disease due to PH1. Levels of plasma oxalate remain elevated for several months after liver transplantation, as the residual body oxalate is slowly excreted. Patients with persistent hyperoxaluria after transplant often require hemodialysis, and accumulation of residual oxalate in the kidney can induce graft dysfunction. As the native kidneys are the main target of calcium oxalate accumulation, we postulated that removal of native kidneys could drastically decrease total body oxalate levels after transplantation. Here, we report a case of bilateral nephrectomy at the time of combined liver-kidney transplantation in a pediatric PH1 patient. Bilateral nephrectomy induced a rapid decrease in plasma oxalate to normal levels in less than 20 days, compared to the several months reported in the literature. Our results suggest that removal of native kidneys could be an effective strategy to decrease the need for hemodialysis and the risk of renal dysfunction after combined liver-kidney transplantation in patients with PH1.

Topics: Child; Female; Glomerular Filtration Rate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Nephrectomy; Oxalates; Renal Dialysis; Renal Insufficiency

Topics: Female; Humans; Hyperoxaluria, Primary; Infant; Kidney Failure, Chronic; Oliguria; Oxalates; Withholding Treatment

Patients with primary hyperoxaluria (PH) overproduce oxalate which is eliminated via the kidneys. If end-stage kidney disease develops they are at high risk for systemic oxalosis, unless adequate oxalate is removed during hemodialysis (HD) to equal or exceed ongoing oxalate production. The purpose of this study was to validate a method to measure oxalate removal in this unique group of dialysis patients.. Fourteen stable patients with a confirmed diagnosis of PH on HD were included in the study. Oxalate was measured serially in hemodialysate and plasma samples in order to calculate rates of oxalate removal. HD regimens were adjusted according to a given patient's historical oxalate production, amount of oxalate removal at dialysis, residual renal clearance of oxalate, and plasma oxalate levels.. After a typical session of HD, plasma oxalate was reduced by 78.4 ± 7.7%. Eight patients performed HD 6 times/week, 2 patients 5 times/week, and 3 patients 3 times/week. Combined oxalate removal by HD and the kidneys was sufficient to match or exceed endogenous oxalate production. After a median period of 9 months, pre-dialysis plasma oxalate was significantly lower than initially (75.1 ± 33.4 vs. 54.8 ± 46.6 mmol/l, p = 0.02).. This methodology can be used to individualize the dialysis prescription of PH patients to prevent oxalosis during the time they are maintained on HD and to reduce risk of oxalate injury to a transplanted kidney.

Topics: Adult; Female; Hemodialysis Solutions; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalates; Renal Dialysis; Time Factors; Young Adult

Hyperoxaluria is a metabolic disorder that can lead to end stage renal disease (ESRD). It can be either inherited or acquired. Primary hyperoxaluria (PHO) is more common and characterized by an excessive production of oxalate leading to recurrent urolithiasis and progressive nephrocalcinosis. Due to the high rate of consanguineous marriage in Jordan this disease is commonly diagnosed in pediatric nephrology clinics. We aimed to demonstrate the clinical pattern and progression to ESRD in pediatric patients with hyperoxaluria at Queen Rania Abdulla Children Hospital.. Medical records of all patients followed up in the pediatric nephrology clinic with the diagnosis of PHO during the period between September 2007 and March 2013 were reviewed.. There were 70 patients with the diagnosis of PHO, 52.9% were males. The median age at presentation was 3 years ± 3 months with the youngest child being two months old. Diagnosis was made in the first year of life in 15.7% of patients. The most common presenting symptom was hematuria, while 14% of patients were asymptomatic and detected by family screening after the diagnosis of an index case. At the time of initial presentation, 15.7% of patients had ESRD and 25% had impaired renal function. Kidney stones were found in 57% of cases and nephrocalcinosis was found in 37%.. High index of suspicion is needed to diagnose PHO in children presenting with kidney stone or unexplained hematuria. Twenty-four hour urine collection for oxalate are required to make the proper diagnosis. Family screening, when appropriate, is indicated for early detection of PHO.

Topics: Child, Preschool; Female; Humans; Hyperoxaluria, Primary; Jordan; Kidney Failure, Chronic; Male; Oxalates

Type 1 primary hyperoxaluria (PH1) causes renal failure, for which isolated kidney transplantation (KT) is usually unsuccessful treatment due to early oxalate stone recurrence. Although hepatectomy and liver transplantation (LT) corrects PH1 enzymatic defect, simultaneous auxiliary partial liver transplantation (APLT) and KT have been suggested as an alternative approach. APLT advantages include preservation of the donor pool and retention of native liver function in the event of liver graft loss. However, APLT relative mass may be inadequate to correct the defect. We here report the first case of native portal vein embolization (PVE) to increase APLT to native liver mass ratio (APLT/NLM-R). Following initial combined APLT-KT, both allografts functioned well, but oxalate plasma levels did not normalize. We postulated the inadequate APLT/NLM-R could be corrected by trans-hepatic native PVE. The resulting increased APLT/NLM-R decreased serum oxalate to normal levels within 1 month following PVE. We conclude that persistently elevated oxalate levels after combined APLT-KT for PH1 treatment, results from inadequate relative functional capacity. This can be reversed by partial native PVE to decrease portal flow to the native liver. This approach might be applicable to other scenarios where partial grafts have been transplanted to replace native liver function.

Topics: Adult; Combined Modality Therapy; Embolization, Therapeutic; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Oxalates; Portal Vein; Prognosis; Transplantation, Homologous

The infantile form of primary hyperoxaluria type I (PHI) is the most devastating PH subtype leading to early end-stage renal failure and severe systemic oxalosis. Combined or sequential liver-kidney transplantation (LKTx) is the only curative option but it involves substantial risks, especially in critically ill infants. The procedure also requires resources that are simply not available to many children suffering from PHI worldwide. Less invasive and less complex therapeutic interventions allowing a better timing are clearly needed. Liver cell transplantation (LCT) may expand the narrow spectrum of auxiliary measures to buy time until LKTx for infants can be performed more safely.. We performed LCT (male neonate donor) in a 15-month-old female in reduced general condition suffering from systemic oxalosis. Renal replacement therapy, initiated at the age of 3 months, was complicated by continuous haemodialysis access problems. Living donor liver transplantation was not available for this patient. Plasma oxalate (Pox) was used as the primary outcome measure.. Pox decreased from 104.3±8.4 prior to 70.0±15.0 μmol/L from Day 14 to Day 56 after LCT. A significant persistent Pox reduction (P<0.001) comparing mean levels prior to (103.8 μmol/L) and after Day 14 of LCT until LKTx (77.3 μmol/L) was seen, although a secondary increase and wider range of Pox was also observed. In parallel, the patient's clinical situation markedly improved and the girl received a cadaveric LKTx 12 months after LCT. However, biopsy specimens taken from the explanted liver did not show male donor cells by amelogenin polymerase chain reaction.. With due caution, our pilot data indicate that LCT in infantile oxalosis warrants further investigation. Improvement of protocol and methodology is clearly needed in order to develop a procedure that could assist in the cure of PHI.

Topics: Cells, Cultured; Child, Preschool; Female; Follow-Up Studies; Hepatocytes; Humans; Hyperoxaluria, Primary; Infant; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Oxalates; Pilot Projects; Prognosis; Risk Factors; Tissue Donors

To determine the clinical, biological, and radiological futures of primary hyper-oxaluria type 1 in Tunisian children, we retrospectively studied 44 children with primary hyper-oxaluria type 1 who were treated in our center from 1995 to 2009. The diagnosis was established by quantitative urinary oxalate excretion. In patients with renal impairment, the diagnosis was made by infrared spectroscopy of stones or kidney biopsies. The male-to-female ratio was 1:2. The median age at diagnosis was 5.75 years. About 43% of the patients were diagnosed before the age of five years with initial symptoms dominated by uremia. Four patients were asymptomatic and diagnosed by sibling screenings of known patients. Nephrocalcinosis was present in all the patients; it was cortical in 34%, medullary in 32%, and global in 34%. At diagnosis, 12 (27%) children were in end-stage renal disease. Pyridoxine response, which is defined by a reduction in urine oxalate excretion of 60% or more, was obtained in 27% of the cases. In the majority of patients, the clinical expression of primary hyperoxaluria type 1 was characterized by nephrocalcinosis, urolithiasis, and renal failure; pyridoxine sensitivity was associated with better outcome.

Topics: Child, Preschool; Female; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Male; Nephrocalcinosis; Oxalates; Retrospective Studies; Tunisia; Ultrasonography; Uremia; Urolithiasis

Topics: Adult; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Nail Diseases; Oxalates

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease.

Topics: Ascites; Bone Marrow; Granuloma; Hepatomegaly; Humans; Hypercalcemia; Hyperoxaluria, Primary; Hypothyroidism; Kidney Failure, Chronic; Male; Middle Aged; Nephrocalcinosis; Oxalates; Renal Dialysis; Urolithiasis

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive inborn error of the glyoxylate metabolism that is based on absence, deficiency or mislocalization of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase. Hyperoxaluria leads to recurrent formation of calculi and/or nephrocalcinosis and often early end-stage renal disease (ESRD) accompanied by systemic calcium oxalate crystal deposition. In this report, we describe an adult female patient with only one stone passage before development of ESRD. With unknown diagnosis of PH, the patient received an isolated kidney graft and developed an early onset of graft failure. Although initially presumed as an acute rejection, the biopsy revealed calcium oxalate crystals, which then raised a suspicion of primary hyperoxaluria. The diagnosis was later confirmed by hyperoxaluria, elevated plasma oxalate levels and mutation of the AGXT gene, showing the patient to be compound heterozygous for the c.33_34InsC and c.508G > A mutations. Plasma oxalate levels did not decrease after high-dose pyridoxine treatment. Based on this case report, we would recommend in all patients even with a minor history of nephrolithiasis but progression to chronic renal failure to exclude primary hyperoxaluria before isolated kidney transplantation is considered.

Topics: Delayed Diagnosis; Diagnostic Errors; Female; Humans; Hyperoxaluria, Primary; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Nephrocalcinosis; Oxalates; Primary Graft Dysfunction; Treatment Failure

Topics: Birefringence; Bone Marrow; Crystallization; Female; Giant Cells, Foreign-Body; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Oxalates; Pancytopenia; Renal Dialysis; Young Adult

Patients with primary hyperoxaluria may need repeated kidney transplants due to damage from oxalic acid (oxalate) deposits. However, oxalate may also be potentially harmful in all transplant recipients. Determinants of oxalate following transplantation have not been well studied.. Two hundred and twelve recipients admitted for transplantation were included in the study. Blood samples for measurement of oxalate and other relevant laboratory parameters were collected at baseline and subsequently 10 weeks after transplantation. For oxalate determination, samples were obtained in 99, 167 and 54 patients out of the 212 at baseline, at follow-up and at both time points, respectively. We examined the bivariate association between plasma oxalate at transplantation and preemptive transplantation, time on dialysis, recipient age, creatinine, urea, phosphate, haemoglobin, PTH, albumin and calcium. Oxalate 10 weeks after transplantation was tested likewise including also laboratory parameters at baseline, primary non-function, rejection episodes, live versus deceased donor, donor age and GFR at follow-up.. Median plasma oxalate concentration at transplantation was 35.0 micromol/L [95% confidence interval (95% CI) = 10.4-93.9] and 98% of the values were above normal limits (2.6-11.0). Oxalate concentration after 10 weeks was 9.0 micromol/L (4.0-25.5), still 37% being above the upper normal value. Multiple regression analysis revealed established dialysis treatment (P = 0.002) and creatinine (P < 0.000001) as independent positive determinants of oxalate at transplantation. Oxalate at 10 weeks was negatively associated to (51)Cr-EDTA absolute GFR (P = 0.023) and positively associated to donor age (P = 0.027) and plasma creatinine at 10 weeks (P = 0.03).. At transplantation, plasma oxalate was on average three times increased and above the upper normal limit in 98% of patients and were still above normal in 37% after 10 weeks. The reduction after 10 weeks is determined by GFR and donor age. Whether increased plasma oxalate following kidney transplantation may have long-term consequences needs further study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalates; Prospective Studies; Regression Analysis; Renal Dialysis; Retrospective Studies; Time Factors; Young Adult

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life-table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976-2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1-, 3- and 5-year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death-censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000-09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses.

Topics: Adolescent; Adult; Aged; Female; Graft Rejection; Graft Survival; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Infant; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Oxalates; Recurrence; Transaminases

Primary hyperoxaluria (PH) is a rare autosomal recessive disease caused by the functional defect of alanine-glyoxylate aminotransferase (AGT) enzyme in the liver and it is characterized by the deposition of diffuse calcium oxalate crystals. A 38-year-old male patient presented with history of recurrent nephrolithiasis and has received chronic hemodialysis treatment for 2 years. Cadaveric renal transplantation was applied to the case. The patient was reoperated on postoperative day 13 because of the collection surrounding the urethra. During this operation, kidney biopsy was made due to late decrease in creatinine levels. Deposition of diffuse oxalate crystal was detected in allograft kidney biopsy, whereas in the 0-hour biopsy there were no oxalate crystals. Oxalate level was found to be high in a 24-hour urine specimen (118 mg/L, normal level: 7-44 mg/L). The patient was identified with primary hyperoxaluria and followed up in terms of systemic oxalate deposition as well as allograft kidney. In the kidney biopsy taken after 18 months, we detected that oxalate crystals almost entirely disappeared. In our case, bilateral preretinal, intraretinal, and intravascular diffuse oxalate crystals were detected, and argon laser photocoagulation treatments were needed for choroidal and retinal neovascularization. Repeated ophthalmic examinations showed the regressive nature of oxalate depositions. In the 18th month, fundus examination and fluorescein angiography revealed that oxalate crystals were significantly regressed. To increase the quality of life and slow down the systemic effects of oxalosis, kidney-only transplantation is beneficial.

Topics: Adult; Coronary Vessels; Humans; Hyperoxaluria, Primary; Kidney; Kidney Calculi; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Retina; Transplantation, Homologous; Ultrasonography

Two unrelated Ragdoll cat mothers in Norway were found dead from renal disease. The histopathology was consistent with oxalate nephrosis with chronic or acute-on-chronic underlying kidney disease. Both cats had offspring and relatives with signs of urinary tract disease, including a kitten dead with urethral gravel. Eleven living Ragdoll cats, including nine relatives of the dead cats and the male father of a litter with similarly affected animals, were tested for primary hyperoxaluria (PH) type 1 and 2 by urine oxalate and liver enzyme analysis. Renal ultrasound revealed abnormalities in five living cats. One of these was azotaemic at the time of examination and developed terminal kidney disease 9 months later. A diagnosis of PH was excluded in 11 cats tested. The inheritance and aetiological background of the renal disease present in the breed remains unresolved at this point in time.

Topics: Animals; Cat Diseases; Cats; Female; Hyperoxaluria, Primary; Kidney Failure, Chronic; Male; Nephrosis; Norway; Oxalates; Ultrasonography

Topics: Adolescent; Creatinine; Female; Humans; Hyperoxaluria; Kidney Failure, Chronic; Oxalates; Skin

Topics: Colonoscopy; Crohn Disease; Diagnosis, Differential; Humans; Kidney Calculi; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Risk Factors; Tomography, X-Ray Computed

Hyperoxaluria can result in the deposition of oxalate in bones, arteries, eyes, heart, nerves, kidneys and other structures when there is a reduction in glomerular filtration rate. Liver and kidney transplantation is curative for patients with Type I primary hyperoxaluria. Here we report a case of recurrent oxalosis in a post-transplant kidney with early graft failure in an adult male.

Topics: Adult; Biopsy; Diagnosis, Differential; Follow-Up Studies; Humans; Hyperoxaluria; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Male; Oliguria; Oxalates; Ultrasonography, Doppler

The goal of this work is to analyze clinical and therapeutics particularities of primary hyperoxaluria in children in Tunisian centre.. We studied retrospectively 15 cases of primary hyperoxaluria enrolled during 9 years period (1994-2002).. It is about 2 boys and 13 girls (sex - ratio = 4.5) aged 2 month to 13 years (mean age: 4 years). Six patients presented the infantile form and nine the juvenile form of HP. At the moment of diagnosis, renal function was normal in one patient, moderately altered in another and severely altered in the other patients. All patients had nephrocalcinosis and 6 among them radio-opaque renal calculi associated. Diagnosis of HP was established in 11 cases by hyperoxaluria and/or important hyperoxalemia or on the data of the renal biopsy and biochemical analysis of renal calculi in 4 cases. The so-called "maghrebin" mutation (Ile244Thr) sought-after in 9 children, has cannot be identified that in 2 among them. Eight patients died of the continuations of their illness. The seven other patients again in life present a terminal renal insufficiency treated by haemodialysis. No patient could benefit from organ transplantation.. Primary hyperoxaluria is a very heterogeneous disease on the plan clinic that genetic. In Tunisia where it constitutes a frequent cause of end stage renal failure, prenatal diagnosis of this disease is of a big interest.

Topics: Adolescent; Biopsy; Child; Child, Preschool; Female; Humans; Hyperoxaluria, Primary; Infant; Isoleucine; Kidney; Kidney Calculi; Kidney Failure, Chronic; Male; Mutation; Nephrocalcinosis; Oxalates; Retrospective Studies; Survival Rate; Threonine; Tunisia

The rate of oxalate absorbed from intestine is highly influenced by calcium intake in healthy subjects. It is unknown whether commonly used phosphate binders modify intestinal absorption and renal excretion of oxalate in chronic kidney disease (CKD) patients. This study aims to determine if calcium carbonate or sevelamer influences on urinary oxalate excretion. Twenty patients with CKD (stage 4 and 5 pre-dialysis) were included. Two treatment (1500 mg of calcium carbonate or 2400 mg of sevelamer), two-period (21 days each), crossover study with balanced assignment of the order of administration, and two washout periods were the main characteristics of this study design. Laboratory analyses in each phase included: serum creatinine, calcium, phosphorus, bicarbonate, total cholesterol, and 24 h urinary excretion of oxalate, creatinine, and urea. Creatinine clearance, protein catabolic rate (PNNA), total urinary oxalate excretion, and urinary oxalate / creatinine ratio were determined. Seventeen patients completed both treatment sequences. Total urinary oxalate excretion and urinary oxalate / creatinine ratios decreased significantly with respect to washout periods either after sevelamer or calcium carbonate treatment. The decrease in urinary oxalate excretion was greater after calcium carbonate (41.2+/-17.4%) than after sevelamer treatment (30.4+/-23.8%). There were not significant changes in renal function or PNNA values throughout the study periods. In conclusion, either calcium carbonate or sevelamer significantly reduces urinary oxalate excretion in CKD patients. Further studies will be needed to ascertain whether the type of phosphate binder influences on the accumulation of oxalate in CKD patients.

Topics: Calcium Carbonate; Chelating Agents; Cross-Over Studies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Polyamines; Sevelamer

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

Topics: Adolescent; Adult; Female; Follow-Up Studies; Hospitals, University; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Mutation; Oxalates; Polymorphism, Genetic; Retrospective Studies; Spain; Survival Analysis; Time Factors; Transaminases; Treatment Outcome

Topics: Biopsy; Diagnosis, Differential; Humans; Hyperoxaluria, Primary; Infant; Kidney; Kidney Failure, Chronic; Male; Oxalates; Severity of Illness Index

Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1) receive dialysis while waiting for transplantation. So far, dialysis has not been shown to overcome the problem of ongoing oxalate production and deposition at extrarenal sites. We report on six children with PH1 who had to be dialyzed for a median period of 2.5 years while awaiting liver transplantation. Aiming at preventing oxalate tissue accretion, oxalate mass transfer was studied and dialysis intensified accordingly. Mean plasma oxalate concentration was between 51 and 137 micromol/l. In three of the six patients with a urinary output between 630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4 mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis (PD) in two of the six patients showed mean oxalate clearances of 66 and 103 l/week/1.73 m2. One patient received HD and PD. By adding all modes of elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2 was removed. Dialysis is still necessary as a temporary therapy for a number of patients with PH1. Dialysis should be instituted pre-emptively and maximally exploited by intensified HD/PD treatment protocols, without, however, cutting back urinary output.

Topics: Child; Child, Preschool; Female; Humans; Hyperoxaluria, Primary; Infant; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Renal Dialysis; Renal Replacement Therapy; Time Factors

Ethylene glycol (EG) consumption is commonly employed as an experimental regimen to induce hyperoxaluria in animal models of calcium oxalate nephrolithiasis. This approach has, however, been criticized because EG overdose induces metabolic acidosis in humans. We tested the hypothesis that EG consumption (0.75% in drinking water for 4 wk) induces metabolic acidosis by comparing arterial blood gases, serum electrolytes, and urinary chemistries in five groups of Sprague-Dawley rats: normal controls (CON), those made hyperoxaluric (HYP) with EG administration, unilaterally nephrectomized controls (UNI), unilaterally nephrectomized rats fed EG (HRF), and a metabolic acidosis (MA) reference group imbibing sweetened drinking water (5% sucrose) containing 0.28 M NH4Cl. Arterial pH, plasma bicarbonate concentrations, anion gap, urinary pH, and the excretion of titratable acid, ammonium, phosphate, citrate, and calcium in HYP rats were not significantly different from CON rats, indicating that metabolic acidosis did not develop in HYP rats with two kidneys. Unilateral nephrectomy alone (UNI group) did not significantly affect arterial pH, plasma bicarbonate, anion gap, or urinary pH compared with CON rats; however, HRF rats exhibited some signs of a nascent acidosis in having an elevated anion gap, higher phosphate excretion, lower urinary pH, and an increase in titratable acid. Frank metabolic acidosis was observed in the MA rats: decreased arterial pH and plasma HCO3(-) concentration with lower urinary pH and citrate excretion with elevated excretion of ammonium, phosphate and, hence, titratable acid. We conclude that metabolic acidosis does not develop in conventional EG treatments but may ensue with renal insufficiency resulting from an oxalate load.

Topics: Acidosis; Animals; Carbon Dioxide; Disease Models, Animal; Electrolytes; Ethylene Glycol; Hyperoxaluria; Kidney Calculi; Kidney Failure, Chronic; Kidney Function Tests; Male; Oxalates; Oxygen; Rats; Rats, Sprague-Dawley

Anemia is an important cause of morbidity in patients suffering from chronic renal failure, and erythropoietin is a milestone of anemia treatment. Various factors may cause erythropoietin resistance. Herein, we describe the case of 32-year-old man who presented with anemia and weakness. He developed progressive renal failure secondary to recurrent kidney stones. One year before admission, he developed anemia for which he had been treated with erythropoietin. However, the anemia persisted. Examination of bone marrow biopsy specimen showed that the marrow was extensively replaced with oxalate crystals and fibrous connective tissue with severe decrease of hematopoietic cells. To the best of our knowledge, our patient represents the first case in the literature describing the association between the oxalate deposition and EPO resistance.

Topics: Adult; Anemia; Biopsy, Needle; Bone Marrow Diseases; Chronic Disease; Drug Resistance; Erythropoietin; Follow-Up Studies; Humans; Hyperoxaluria; Immunohistochemistry; Kidney Calculi; Kidney Failure, Chronic; Male; Oxalates; Renal Dialysis; Risk Assessment; Severity of Illness Index; Treatment Failure

Topics: Designer Drugs; Genetic Therapy; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Oxalates; Transaminases

The precise nature of band 3 protein and its involvement in oxalate exchange in the red blood cells (RBCs) of renal failure patients has not been studied in detail. Therefore, here we studied the oxalate exchange and binding by band 3 protein in RBCs of humans with conditions of acute and chronic renal failure (ARF and CRF). The RBCs of ARF and CRF patients exhibited abnormal red cell morphology and an increased resistance to osmotic hemolysis. Further, an increase in the cholesterol content and decrease in the activities of Na(+)-K(+)-, Ca(2+)-, and Mg(2+)-ATPases of membranes were observed in the RBCs of ARF and CRF patients. A decrease in the oxalate flux was observed in the RBCs of ARF and CRF patients. The oxalate-binding activities of the RBC membranes were significantly lower in ARF (20 pmoles/mg protein) and CRF (5.3 pmoles/mg protein) patients as compared to that in the normal subjects (36 pmoles/mg protein). DEAE-cellulose and Sephadex G-200 column chromatography purification profiles revealed a distinctive shift in oxalate-binding activity of band 3 protein of RBCs of ARF and CRF patients as compared to that of the normal subjects. It was also observed from the binding studies with a fluorescent dye, eosin-5-maleimide, which specifically binds to band 3 protein, that the RBCs of ARF and CRF patients exhibited only 53 and 32% of abundance of band 3 protein, respectively, as compared to that in the RBCs of the normal subjects, thus revealing a decrease in the band 3 protein content in ARF and CRF patients. These results for the first time showed a decrease in the oxalate exchange in RBCs of patients with ARF and CRF, which was also concomitant with the low levels of abundance of band 3 protein.

Topics: Acute Kidney Injury; Anion Exchange Protein 1, Erythrocyte; Eosine Yellowish-(YS); Erythrocyte Membrane; Erythrocytes; Female; Fluorescent Dyes; Hemolysis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates

Combined liver and kidney transplantation is the ideal treatment for patients with end-stage renal failure secondary to primary hyperoxaluria and systemic oxalosis, with a functioning liver providing replacement of the deficient enzyme and a functioning kidney providing the route of excretion for the oxalate crystals. Pancytopenia from bone marrow infiltration of oxalate crystals is a rare complication of primary hyperoxaluria, and its reversal following transplant has not been described. We report the first case of pancytopenia from marrow infiltration by oxalate crystals reversing following a successful kidney transplant alone. Although kidney alone transplants do not provide the best chance of survival or quality of life as compared to a combined kidney and liver transplant, a well functioning kidney transplant is able to take care of the systemic oxalate load and ameliorate, at least for a period of time, the systemic complications of oxalosis.

Topics: Adult; Bone Marrow; Crystallization; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Pancytopenia; Recurrence

Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder in which deficiency of the liver enzyme AGT leads to renal failure and systemic oxalosis. Timely, combined cadaveric liver-kidney transplantation (LKT) is recommended for end-stage renal failure (ESRF) caused by PH1; however, the shortage of cadaveric organs has generated enthusiasm for living-related transplantation in years. Recently, successful sequential LKT from the same living donor has been reported in a child with PH1. We present a sister-to-brother simultaneous LKT in a pediatric patient who suffered from PH1 with ESRF. Twelve months after transplantation, his daily urine oxalate excretion was decreased from 160 mg to 19.5 mg with normal liver and renal allograft functions. In addition to the well-known advantages of living organ transplantation, simultaneous LKT may facilitate early postoperative hemodynamic stability and may induce immunotolerance and allow for low-dose immunosuppression.

Topics: Adult; Child; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Living Donors; Male; Oxalates; Time Factors; Treatment Outcome

Enteric secretion of oxalate is induced in rats that have chronic renal failure produced by 5/6 nephrectomy. The purpose of the present study was to examine renal and intestinal handling of oxalate in rats with chronic renal failure (CRF) induced by chronic hyperoxaluria. A rat model for chronic renal failure, induced by chronic hyperoxaluria (CH-CRF), was produced by unilateral nephrectomy combined with dietary ethylene glycol for 4 weeks. Both intact and unilateral nephrectomized rats (UN) without the oxalate load served as controls. Renal handling of oxalate was assessed by measurement of renal clearance of oxalate and creatinine while colonic handling of oxalate and chloride was determined by in vitro transepithelial flux measurements. Angiotensin II mediation was assessed by sensitivity of the transport processes to the AT(1) receptor antagonist losartan. Renal and colonic handling of oxalate in UN rats were similar to intact controls. The CH-CRF rats were hyperoxalemic, hyperoxaluric, and exhibited a twofold increase in oxalate clearance despite a 50% drop in creatinine clearance. Distal (but not proximal) colonic handling of oxalate in CH-CRF rats was reversed from net oxalate absorption seen in UN and intact controls to net secretion that was sensitive to losartan in vitro.. Although enteric oxalate secretion can be correlated with elevations in plasma oxalate in the absence of overt renal insufficiency by an ANG II-independent mechanism, the present results suggest that some degree of renal insufficiency is necessary to induce ANG II-mediated colonic oxalate secretion.

Topics: Adaptation, Physiological; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Biological Transport; Chlorides; Colon; Creatinine; Hyperoxaluria; Intestinal Absorption; Kidney; Kidney Failure, Chronic; Losartan; Male; Osmolar Concentration; Oxalates; Rats; Rats, Sprague-Dawley

We present a case of a patient with short bowel syndrome in a hemodialysis program, with recurrent episodes of serious acidosis. The presence of a D-lactic acidosis peak secondary to bacterial overgrowth in the intestine was discovered during an acute episode of acidosis, with neurological affection. The detection of acidosis in predialysis measurements and the acute episodes of acidosis, made it necessary to administer bicarbonate to the patient and give him additional hemodialysis sessions.

Topics: Acidosis, Lactic; Adult; Bicarbonates; Brain Diseases, Metabolic; Consciousness Disorders; Drug Therapy, Combination; Dysarthria; Gram-Positive Bacteria; Humans; Intestines; Kidney Failure, Chronic; Lactates; Male; Neomycin; Oxalates; Paromomycin; Recurrence; Renal Dialysis; Short Bowel Syndrome; Urinary Calculi

The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available.. Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation.. PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03).. The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.

Topics: Adolescent; Adult; Calcium; Calcium Oxalate; Child; Child, Preschool; Citric Acid; Crystallization; Female; Humans; Hyperoxaluria; Kidney Failure, Chronic; Magnesium; Male; Osmolar Concentration; Oxalates; Phenotype; Urinary Calculi; Urine

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.

Topics: Acute Kidney Injury; Biopsy; Female; Humans; Hyperoxaluria, Primary; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Oxalates; Renal Dialysis

Topics: Child; Female; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Oxalates

Children with primary hyperoxaluria type 1 (PH 1) are at great risk to develop systemic oxalosis in end-stage renal disease (ESRD), as endogenous oxalate production exceeds oxalate removal by dialytic therapy. As oxalate accumulates, calcium oxalate (CaOx) tissue deposition occurs. Children with other causes of ESRD, however, are not prone to CaOx deposition despite elevated plasma oxalate (POx) levels.. Our study objective was to examine the potential mechanisms for these observations. We measured POx, sulfate, citrate, and calculated CaOx saturation (betaCaOx) in 7 children with ESRD caused by PH 1 and in 33 children with non-PH-related ESRD. Maintenance hemodialysis (HD) was performed in 6 PH 1 and 22 non-PH patients: Pre- and post-HD levels were analyzed at this point and were repeated twice within 12 months in 5 PH 1 and 14 non-PH patients. Samples were obtained only once in 12 patients (one PH 1) on peritoneal dialysis (PD). After liver-kidney or kidney transplantation, plasma levels were measured repetitively.. The mean POx was higher in PH 1 (125.7 +/- 17.9 micromol/liter) than in non-PH patients (44.2 +/- 3.3 micromol/liter, P < 10(-4)). All other determined anions did not differ between the two groups. betaCaOx was higher in PH 1 (4.71 +/- 0.69 relative units) compared with non-PH children (1.56 +/- 0.12 units, P < 10(-4)). POx and betaCaOx were correlated in both the PH 1 (r = 0.98, P < 2 x 10(-4)) and the non-PH group (r = 0.98, P < 10(-4)). POx and betaCaOx remained stable over time in the non-PH children, whereas an insignificant decline was observed in PH 1 patients after six months of more aggressive dialysis. betaCaOx was supersaturated (more than 1) in all PH 1 and in 25 out of 33 non-PH patients. Post-HD betaCaOx remained more than 1 in all PH 1, but in only 2 out of 22 non-PH patients. In non-PH children, POx and betaCaOx decreased to normal within three weeks after successful kidney transplantation, whereas the levels still remained elevated seven months after combined liver-kidney transplantation in two PH 1 patients.. Systemic oxalosis in PH 1 children with ESRD is due to higher POx and betaCaOx levels. As betaCaOx remained supersaturated in PH 1 even after aggressive HD, oxalate accumulation increases, and CaOx tissue deposition occurs. Therefore, sufficient reduction of POx and betaCaOx is crucial in PH 1 and might only be achieved by early, preemptive, combined liver-kidney transplantation or liver transplantation alone.

Topics: Bone and Bones; Calcium Oxalate; Child; Female; Humans; Hyperoxaluria, Primary; Infant; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Renal Dialysis; Retina

Enteric excretion of oxalate was studied in rats with chronic renal failure (CRF) by measuring the magnitude and direction of oxalate fluxes in vitro across short-circuited preparations of distal colon in Ussing chambers. The net absorptive flux of oxalate that is characteristic of colonic tissues removed from control rats was significantly changed to a net secretory flux in CRF rats. Injecting CRF rats with a specific angiotensin II (AngII) receptor (AT1) antagonist, losartan, results in a reversal of the CRF-induced net secretory flux (-13.87+/-0.08 pmol x cm(-2) x h(-1)) to an absorptive flux (+7.32+/-3.68 pmol x cm(-2) x h(-1)) by normalizing the unidirectional fluxes of oxalate. Similarly, oxalate fluxes were normalized across CRF colonic tissues by acute, in vitro application of losartan to the serosal bathing solution. It was also possible to simulate the CRF-induced secretory flux of oxalate (Jsm) in vitro across colonic tissues removed from control rats. Serosal application of AngII at 10(-6), 10(-5), and 10(-4) M resulted in significant increases in the s-->m flux of oxalate (increasing deltaJsm = 4.06+/-1.2, 8.41+/-0.94, and 13.8+/-3.8 pmol x cm(-2) x h(-1), respectively). Taken together, these results suggest that CRF-induced oxalate secretion is at least partly mediated by AngII, which is consistent with previous findings of a twofold upregulation of AT1 receptors in CRF colonic mucosa.

Topics: Angiotensin II; Animals; Colon; Kidney Failure, Chronic; Male; Oxalates; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin

We present the case of a young woman who developed renal failure of unknown cause, and after 2 months of maintenance hemodialysis developed livedo reticularis, retinopathy, and peripheral sensory neuropathy. The patient was subsequently shown to have primary oxalosis type I, a rare autosomal recessive error of metabolism characterized by accumulation of calcium oxalate crystals in the kidneys, eyes, skin, and other organs. Intravascular obstruction, caused by deposition of calcium oxalate crystals in cutaneous arterioles, is thought to be responsible for the ischemic livedo reticularis lesions observed in this patient. A method is described for measuring serum glycolate by isotope dilution gas chromatography-mass spectrometry (GC-MS). An approach to the diagnosis and management is also briefly mentioned.

Topics: Adult; Diagnosis, Differential; Female; Glycolates; Humans; Hyperoxaluria; Kidney Failure, Chronic; Oxalates; Peripheral Nerves; Renal Dialysis; Retinal Diseases; Sensation Disorders; Skin Diseases, Vascular

Primary hyperoxaluria type 1 (PH 1) is complicated by a high rate of early end-stage renal failure (ESRF). In ESRF combined liver kidney transplantation has emerged as treatment of choice for teenagers and adults. In chronic renal failure (CRF) and for small children the situation is less clear. We report on three isolated liver transplantations and show the data of young children from the European Registry for liver transplantation in PH 1. Patient #1 developed ESRF at 3 months of age. Deficiency of alanine:glyoxylate aminotransferase proved PH 1. Progressive bone disease developed and the boy received a living related liver graft (LRLTx) at age two. Due to recurrent cholangitis kidney transplantation (KTx) is currently not feasible. Plasma oxalate decreased after LRLTx indicating correction of the metabolic defect. Patient #2 was diagnosed at the age of 14 months. He had nephrocalcinosis and hyperglycolic hyperoxaluria. Two years later he developed ESRF. At 5 years of age isolated liver transplantation was performed as a first step of therapy. Due to prolonged warm ischemia time organ function was poor. A severe bleeding complicated the course. The child died four weeks after transplantation from untreatable CMV septicemia. Patient #3 was evaluated for failure to thrive at 6 months of age. Urinary oxalate/creatinine ratio was 705 mumol/mol and gave rise to the diagnosis of PH 1. Renal failure slowly progressed to a creatinine clearance of 20 ml/min/1.73 m2 at 8 years, when liver transplantation (LTx) was performed. Four months later, GFR has not changed. Liver function and urinary oxalate/creatinine ratio are normal. Slowly deteriorating chronic renal failure can be stabilized through isolated liver transplantation and thus the rapid need for KTx will at least be delayed. Even more important, normalization of the oxalate metabolism prevents extrarenal oxalate deposits during renal failure.

Topics: Child; Fatal Outcome; Female; Humans; Hyperoxaluria, Primary; Infant; Kidney Failure, Chronic; Liver Transplantation; Male; Oxalates; Retrospective Studies

Urinary oxalic acid excretion was examined in 61 patients with chronic nephropathies and in 21 patients after renal transplantation with a varying mean glomerular filtration. In both groups of patients a correlation was found between the plasma oxalic acid and serum creatinine and by a hyperbolic correlation between plasma oxalic acid and creatinine clearance. Moreover the authors found a direct correlation between oxalic acid and FEoxalic acid and FE(Na)+, FEH20 and FE1-ascorbic acid in both patient groups. Various chronic nephropathies and treatment in both groups did not affect the revealed correlations. In 13 healthy subjects during the period of maximum water diuresis urinary Na+ excretion did not increase but there was a significant increase of the l-ascorbic acid and oxalic acid excretion. In a group of 8 patients in the polyuric stage of chronic renal failure without dialysis treatment under conditions of increased dietary NaCl intake (15 g/24 h) a significant increase of the urinary Na+ excretion was recorded while the l-ascorbic acid and oxalic acid excretion was unaltered. From the assembled values of the examined biochemical indicators ensues that urinary oxalic acid excretion, similarly as ascorbic acid excretion, depended on water excretion.

Topics: Adult; Ascorbic Acid; Creatinine; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalates; Oxalic Acid; Sodium

Primary hyperoxaluria (PH) type 1 and type 2 are autosomal recessive defects of oxalate metabolism resulting from glyoxylate accumulation which occurs by two distinct pathways. PH1 is associated to glycolic aciduria; PH2 to L-glyceric aciduria. Because hyperoxaluria leads to nephrolithiasis or nephrocalcinosis in both, they can be differentiated only through detection of the associated acidurias. However, glycolate and L-glycerate assays are not widely available and, in the setting of ESRF, diagnosis is hampered by a number of misleading events. At any stage of the disease diagnosis is crucial because there are differences between the two forms in clinical behaviour, long-term prognosis, and treatment. In this paper we outline diagnostic criteria for identification of PH2 in two patients, one with maintained renal function and one with ESRF on CPD, based on the use of a novel HPLC assay of L-glycerate in different body fluids. With the routine application of this procedure PH2 has been identified in two of 23 patients fulfilling criteria for diagnosis of PH. This suggests that the type 2 variant of PH may occur more frequently than so far suspected, and should be tested for even in the setting of ESRF.

Topics: Child, Preschool; Female; Glyceric Acids; Glycolates; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Renal Replacement Therapy

Estimating calcium oxalate saturation (beta CaOx) in body fluids is proposed as a simple and reproducible procedure to assess the risk of systemic oxalosis in several clinical conditions associated with oxalate retention. beta CaOx was computerized from the measured concentrations of main serum ions. Accurate assay of serum oxalate was crucial for reliability of beta CaOx estimates. However, beta CaOx also depended upon changes of calcium and magnesium concentrations. Patients with end-stage renal failure (ESRF) due to primary or enteric hyperoxaluria had beta CaOx greater than saturation, whereas this happened in only 10 of 25 and two of 24 of those with oxalosis-unrelated ESRF. Bony content of oxalate measured in some of these patients was consistent with these results. In patients with maintained renal function beta CaOx was inversely related to glomerular filtration rate, but the slope was steeper in patients with than in those without hyperoxaluria and beta CaOx reached saturation at earlier stages of renal insufficiency.

Topics: Calcium Oxalate; Humans; Hyperoxaluria; Kidney Failure, Chronic; Oxalates; Peritoneal Dialysis; Renal Dialysis

The extrarenal elimination of oxalate via the intestine was studied in rats with chronic renal failure by measuring the magnitude and direction of oxalate fluxes across the small and large intestine. Oxalate transport was determined in vitro across short-circuited sheets of jejunum, ileum, and colon that were placed in Ussing chambers. The concentration of oxalate in plasma and urine was measured immediately before the transport studies. The results show that, 6 wk after 5/6 nephrectomy, rats with chronic renal failure have lower (decreases 50%) renal clearance of oxalate and a higher mean plasma oxalate concentration (increases 80%) than controls. The basal absorption of oxalate across the colon was changed to secretion in animals with chronic renal failure (from 12.81 +/- 2.22 (N = 9) to -14.96 +/- 2.57 (N = 11) pmol/cm2 per hour). Both the jejunum and the ileum supported a basal net secretory flux of oxalate (-19.71 +/- 2.39 (N = 13) and -30.06 +/- 2.80 (N = 16) pmol/cm2 per hour) that was unaffected by renal insufficiency. These studies demonstrate that intestinal transport systems for oxalate are altered in experimental chronic renal failure, and the distal colon is identified as the primary site for this adaptive response. In chronic renal failure, the entire intestinal tract can potentially excrete oxalate.

Topics: Animals; Creatinine; Intestine, Large; Intestine, Small; Kidney Failure, Chronic; Male; Oxalates; Rats; Rats, Sprague-Dawley

We use oxalate oxidase from barley seedlings for the colorimetric determination of oxalate in plasma. The oxalate is converted to hydrogen peroxide, which, in the presence of peroxidase, is detected by a Trinder-like chromogenic system. Optimization of the assay, including deproteinization and elimination of interferences from reducing substrates, is described. Ascorbate additions (200 mumol/L) did not affect oxalate concentration in plasma, even after long frozen storage. Mean analytical recovery of oxalate averaged 102% +/- 6.9%, imprecision (CV) at 2.0 mumol/L was 7.2%, and the lower limit of quantification (CV = 20%) was 0.6 mumol/L. Results correlated well with those by chromatography (r = 0.999, Sy/x = 0.29 mumol/L, n = 32, range for x, y = 0-140 mumol/L). Plasma oxalate concentrations measured in 32 healthy subjects ranged from 0.6 to 2.9 mumol/L (mean 1.28, SD 0.71 mumol/L), which agrees with those measurable by using indirect radioisotopic dilution methods. Patients with primary hyperoxaluria and chronic renal failure exhibited markedly greater plasma concentrations of oxalate.

Topics: Adolescent; Adsorption; Adult; Ascorbic Acid; Benzenesulfonates; Blood Proteins; Charcoal; Child; Chromogenic Compounds; Colorimetry; Drug Stability; Female; Freezing; Hordeum; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Oxidoreductases; Quality Control; Reference Values; Salicylates; Sensitivity and Specificity

We tested the possibility that the buffering agents in dialysis bath fluid might contribute to increased endogenous oxalate production in dialyzed patients. Using stable isotope dilution mass spectrometry, we obtained oxalate production rates and pool sizes directly for 10 patients in chronic renal failure, 5 of whom were undergoing continuous ambulatory peritoneal dialysis (lactate-buffered fluid). All peritoneal dialysis patients had either increased oxalate production rates or expanded oxalate pools when compared with undialyzed patients in renal failure. From a further four patients receiving maintenance hemodialysis we took blood samples immediately before and after three consecutive dialysis sessions in which the bath-fluid buffering agent (bicarbonate or acetate) was alternated; we analyzed these samples for oxalate and key precursors by capillary gas chromatography. Plasma glycine and serine concentrations remained within the physiological range. Glycolate and oxalate concentrations decreased, but the oxalate remained above normal after dialysis. All changes were independent of the bath-fluid buffering agent. We suggest that dialysis might stimulate the formation of oxalate by removing product inhibition of a late catabolic step.

Topics: Acetates; Bicarbonates; Buffers; Dialysis Solutions; Female; Glycolates; Humans; Indicator Dilution Techniques; Kidney Failure, Chronic; Kinetics; Male; Mass Spectrometry; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory

Topics: Adolescent; Child; Child, Preschool; Creatinine; Female; Graft Rejection; Graft Survival; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Oxalates; Quality of Life; Time Factors

Topics: Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Middle Aged; Oxalates

A 15-year-old patient with severe bone disease (with bilateral fractures of hips and shoulders) due to primary hyperoxaluria type 1 (PH1) was treated with combined liver-kidney transplantation after a 4-year hemodialysis period. Normalization of excessive oxalate synthesis brought in by the liver graft combined with the slow excretion of skeletal oxalate stores by the renal graft led to progressive improvement of clinical, radiological, and histological evidence of oxalate osteopathy. This allowed bilateral hip replacement 3 years after transplantation, which led to complete physical rehabilitation of the crippled patient. Combined liver-kidney transplantation constitutes the treatment of choice for end-stage renal failure due to PH1, even in the face of severe oxalate bone disease.

Topics: Adolescent; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Creatinine; Female; Femur Head; Hip Fractures; Hip Prosthesis; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Oxalates; Shoulder Fractures

We describe the case of a patient in end-stage renal failure due to primary hyperoxaluria type I (PH1) who started hemodialysis in 1977 and is still alive and active. The diagnosis of PH1 was first suspected after a bone biopsy performed in 1981 to investigate hyperparathyroidism. Oxalosis recurred as early as 3 months after transplantation in a cadaver kidney grafted in 1987; nevertheless, graft function remained good enough to make possible the discontinuation of dialysis treatment for 5 months and thereafter to have only 1 dialysis a week for 17 months. The diagnosis of PH1 has been recently confirmed despite the patient being already anuric by means of the determination of plasma oxalate and glycolate levels as well as by determining hepatic alanine:glyoxylate amino-transferase.

Topics: Adult; Alanine; Glycolates; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver; Male; Oxalates; Renal Dialysis; Time Factors; Transaminases

We assessed plasma levels and removal rates of oxalate in 24 patients on chronic peritoneal dialysis (CPD) for oxalosis-unrelated renal failure. The ion-chromatographic (IC) measurements of oxalate in plasma, dialysate, and urine (in seven patients with residual renal function) were used to calculate peritoneal and renal clearances of oxalate. The serum state of saturation with calcium oxalate was calculated by means of a computer-based model system. Patient data were compared with those from 19 healthy individuals. Peritoneal clearance of oxalate was 6.3 +/- 4.7 mL/min, ie, 8% of the normal renal clearance. As a result, both plasma oxalate and calcium oxalate saturation were higher than in controls and did not overlap. Plasma was supersaturated with calcium oxalate in only two of 24 patients (8%). Removal of oxalate by dialysis was related to the amount of fluid infused. Overall removal of oxalate (dialysate plus urine) was similar to 24-hour excretion of normal subjects and was taken as a measure of its generation. Oxalate generation rate was dependent on protein (whole and animal) intake, but not on caloric intake or pyridoxine status. Pyridoxine supplementation, 75 and 300 mg daily for 1 months, was not effective in reducing plasma levels or generation rates of oxalate. Residual renal function had a minor influence on oxalate patterns. We conclude that current programs are adequate to maintain oxalate balance in patients on CPD under basic conditions.

Topics: Adult; Aged; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Peritoneal Dialysis; Urea

Topics: Adult; Crohn Disease; Humans; Kidney Failure, Chronic; Male; Oxalates; Pyridoxine; Renal Dialysis

On the occasion of a combined liver-kidney graft doing well after 3 years, the molecular anomalies responsible for primary hyperoxaluria type 1 are discussed. This rare condition may be listed in the expanding group of hereditary diseases involving peroxisomes, cellular organelles with increasingly recognised functions. Recent progress in the molecular biology of this disease have led to the proposal of of new transplant strategies for its cure.

Topics: Adult; Combined Modality Therapy; Female; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Microbodies; Oxalates

Whether pyridoxine (B6) supplements decrease plasma oxalate concentrations in patients on maintenance dialysis is unresolved. The effect of two dose levels of B6, 0.59 mmol/day (100 mg/day) over 6 months and 4.43 mmol (750 mg) after each dialysis treatment for 4 wk, on plasma oxalate and oxalate removal rate (dialysis plus urinary excretion) was studied in patients on maintenance hemodialysis. In both studies, a control group unsupplemented with B6, who remained on their regular diet, was also studied. The vitamin B6 status of the patients was assessed by the erythrocyte glutamate pyruvate transaminase activity and index before and during supplementation. No decrease in plasma oxalate or oxalate removal rate was found in either study. The plasma oxalate and oxalate removal rates of the unsupplemented hemodialysis patients were not different from those receiving B6 either before or after supplementation. These studies demonstrate that high-dose B6 supplementation does not decrease plasma oxalate concentration in a population of hemodialysis patients.

Topics: Alanine Transaminase; Creatinine; Humans; Hyperoxaluria; Kidney Calculi; Kidney Failure, Chronic; Oxalates; Pyridoxine; Renal Dialysis; Uremia; Vitamin B 6 Deficiency

Oxalic acid is an end product of metabolism, and no significant degradation of oxalate occurs in mammals. The sole route of oxalate excretion is believed to be via the kidney. The extrarenal clearance of oxalate in control rats (N = 16) and in 5/6 nephrectomized rats (N = 25) with renal insufficiency was investigated. [14C]oxalic acid, approximately 2 microCi/day, was infused sc by a mini osmotic pump over 4 days. Excretion of 14C was measured in urine, in feces, and in expired CO2. The 14C content of kidney, heart, liver, muscle and bone was also determined at the time the animals were killed. Plasma oxalate was determined by an enzymatic method and by an isotopic dilution procedure. Creatinine clearance in the controls was 1.82 +/- 0.1 mL/min (mean +/- SE) compared with 0.31 +/- 0.04 mL/min (P < 0.0005) in the nephrectomized rats. Plasma oxalate was 5.6 +/- 0.6 mumol/L in controls and 27.0 +/- 3.9 (mean +/- SE; N = 24) in nephrectomized animals (P < 0.0005). The total 14C recovered in urine, feces, and CO2 combined was similar in both groups. The 14C excreted in the feces over the 4-day period was 27.8 +/- 1.5% (of the 14C recovered) in rats with renal failure and 6.5 +/- 0.5% in controls (P < 0.0005). Percent fecal 14C excretion in nephrectomized rats was inversely correlated with creatinine clearance (r = 0.80; P < 0.0001) and directly correlated with plasma oxalate (r = 0.66; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biological Transport; Bone and Bones; Feces; Intestinal Mucosa; Kidney Failure, Chronic; Male; Muscles; Nephrectomy; Oxalates; Oxalic Acid; Rats; Rats, Wistar; Tissue Distribution; Urine; Viscera

We studied the effect of vitamin C and B6 supplementation on oxalate metabolism in seven patients receiving chronic peritoneal dialysis therapy. The study was divided into three phases, each lasting 4 weeks. Plasma oxalate, total ascorbic acid, and pyridoxal-5'-phosphate (PLP) were measured at the end of each phase. Twenty-four-hour urinary excretion and dialysate removal rates of oxalate were also obtained. At the end of phase I (supplement-free period), plasma oxalate levels were markedly elevated at 47.6 +/- 7.1 mumol/L (437 +/- 66 micrograms/dL) (normal, 3.4 +/- 0.4 mumol/L [30.3 +/- 1.6 micrograms/dL]). Plasma total ascorbic acid levels were 62 +/- 6 mumol/L (1.0 +/- 0.1 mg/dL) (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]), while plasma PLP levels were markedly reduced to 24 +/- 5 nmol/L (normal, 40 to 80 nmol/L). Daily supplements of 0.57 mmol (100 mg) ascorbic acid orally (phase II) resulted in a 19% increase in the plasma oxalate levels to 57.8 +/- 6.1 mumol/L (520 +/- 55 micrograms/dL) (P less than 0.03), with a concomitant 60% increase in the plasma ascorbate levels (91 +/- 6 mumol/L [1.6 +/- 0.1 mg/dL], P less than 0.01). Plasma PLP values remained low. Finally, during phase III (0.57 mmol or 100 mg ascorbic acid plus 59.6 mumol or 10 mg pyridoxine HCI orally daily), plasma oxalate levels declined by 17% to 47.9 +/- 5.2 mumol/L (431 +/- 47 micrograms/dL) (P greater than 0.05 v phase II).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Ascorbic Acid; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxal Phosphate; Pyridoxine

Regular dialysis treatment (RDT) does not obviate hyperoxalemia of chronic renal failure (CRF). However, there is emerging evidence suggesting that current dialysis prescription is not always associated to progressive oxalate accumulation. In view of the controversy still concerning this issue, we have investigated on plasma profiles and dialysis kinetics of oxalate in patients on RDT. Oxalate was determined by ion chromatography on serum ultrafiltrates and on the whole dialyzate in 23 stable patients on RDT for end-stage renal failure unrelated to primary hyperoxaluria. Nine patients were on traditional hemodialysis (HD) and 14 on soft hemodiafiltration (HDF). Dialysis prescription was set so as to obtain similar KT/V of urea. Mean dialyzer clearance of oxalate (KdOx) was calculated by standard procedures and was compared to urea (KdUrea) and creatinine (KdCr) clearances. Oxalate removal was measured on the whole spent dialyzate. Distribution volume of oxalate (VOx) was estimated by assuming a single-pool model and was used to estimate the oxalate appearance rate (OxAR). Plasma profiles showed that dialysis patients were virtually always hyperoxalemic. However, the threshold of supersaturation for calcium oxalate was exceeded in only 13 of 138 (9.4%) assayed ultrafiltrates, 13% on HD and 7.1% on HDF. Dialysis reduced plasma oxalate by more than 60%. There was a postdialysis oxalate rebound averaging 9.6% at 30 min from the end of dialysis. Plasma oxalate predialysis was independent of sex, age and time on dialysis. KdOx was mildly higher on HDF than on HD, and was lower than both KdUrea and KdCr, irrespective of the dialysis technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chromatography; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Renal Dialysis

Topics: Adult; Alanine Transaminase; Algorithms; Calcium Oxalate; Child; Combined Modality Therapy; Humans; Incidence; Kidney Failure, Chronic; Kidney Transplantation; Liver; Liver Transplantation; Oxalates; Oxalic Acid; Pyridoxine; Transaminases; Urinary Calculi

Two case histories of patients with end-stage renal disease subsequently found to have primary hyperoxaluria are reported. In the setting of renal failure, the diagnosis is both difficult, due to diminished oxalate excretion, and important, because of frequent graft loss due to oxalate deposition after renal transplantation. The diagnosis was obtained by renal and bone biopsies. Plasma oxalate levels were normal in one patient and the other patient presented with extensive cystic bone lesions. Primary hyperoxaluria should be considered whenever nephrocalcinosis and/or nephrolithiasis are associated with end-stage renal disease.

Topics: Adult; Biopsy; Bone and Bones; Female; Humans; Hyperoxaluria, Primary; Kidney; Kidney Calculi; Kidney Failure, Chronic; Kidney Transplantation; Male; Nephrocalcinosis; Oxalates

A 3.5-year-old boy presented with end-stage renal disease and bilateral nephrocalcinosis. Renal biopsy demonstrated marked parenchymal calcium oxalate deposition and a diagnosis of primary hyperoxaluria (PH) was made. Following 2 years of hemodialysis he received two renal allografts which were lost at 7 and 11 months, respectively, due to biopsy-proven recurrent oxalosis. Combined liver-kidney transplantation was then performed, after which renal and hepatic function initially stabilized. The patient died on the 28th postoperative day, of infectious complications and progressive respiratory insufficiency. However, comparisons between the patterns of urinary oxalate excretion noted after the isolated renal and liver-kidney transplants indicated that, following the latter, successful biochemical correction of the enzyme defect responsible for type 1 PH had occurred.

Topics: Child, Preschool; Graft Rejection; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Oxalates; Oxalic Acid; Renal Dialysis; Reoperation

The cause of secondary hyperoxalemia and oxalosis in patients on maintenance dialysis is unknown. The oxalate removal rate was determined in 26 patients on maintenance hemodialysis and 6 on continuous ambulatory peritoneal dialysis by measuring oxalate removed by dialysis and urinary excretion. The role of vitamin B6 deficiency and ascorbate in the raised plasma oxalate concentrations of these patients was evaluated. Plasma oxalate in hemodialysis patients, 442 +/- 41 micrograms/100 mL (mean +/- SE), and peritoneal patients, 394 +/- 115 micrograms/100 mL, were significantly higher than that in normal subjects, 11 +/- 1 microgram/100 mL (P less than 0.001). Average daily oxalate removal in subjects on hemodialysis, based on dialysis losses and urinary excretion, 35 +/- 3 mg/24 h, was significantly greater than urinary excretion of normal subjects, 26 +/- 1 (P less than 0.01). Oxalate removal from peritoneal dialysis patients, 28 +/- 2 mg/24 h, was not significantly different from that of hemodialysis patients or urinary excretion of normal subjects. Plasma ascorbate and B6 status were not correlated with plasma oxalate. A positive correlation between B6 deficiency and oxalate removal rate was not found. Plasma oxalate was correlated with time on dialysis (all patients) (P = 0.02). In a separate study of 15 hemodialysis patients followed over 2.3 +/- 0.2 yr, both plasma oxalate and oxalate removal rate significantly increased, P less than 0.001 and 0.05, respectively. It was concluded that oxalate removal rate is increased in hemodialysis patients and that the increased total body oxalate burden in these patients is not due to decreased removal. Although the increase may result from increased oxalate synthesis or gastrointestinal absorption, B6 deficiency and increased plasma ascorbate do not play a role.

Topics: Alanine Transaminase; Ascorbic Acid; Erythrocytes; Humans; Intestinal Absorption; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Vitamin B 6 Deficiency

Plasma oxalate was measured in 20 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and 20 patients receiving hemodialysis (HD). All patients had levels well above the reference range of less than 2.0 to 5.0 mumol/L (less than 0.18 to 0.44 mg/L), the medians being 34 mumol/L (2.99 mg/L) and 42 mumol/L (3.70 mg/L) for the two groups, respectively. Plasma oxalate did not differ significantly in the two groups. Plasma oxalate was not influenced by the number of months patients had received dialysis treatment, but a significant correlation was found between oxalate and creatinine in the 40 patients studied (P less than 0.02, r = 0.38). Predialysis oxalate levels were reduced by approximately 60% following HD, but returned to 80% of the predialysis levels within 24 hours and 95% within 48 hours. Oxalate levels did not differ significantly in samples taken before, during, and after exchanges of CAPD fluid. That the patients treated with CAPD did not have higher oxalate levels than the HD group suggests that the continuous nature of the former treatment compensates for the lower oxalate clearance by the peritoneum. The reported higher risk of oxalosis associated with intermittent peritoneal dialysis has led to a similar risk being postulated for CAPD; however, the present study indicates that if such a risk exists, it cannot be explained by higher levels of oxalate or ionized calcium in these patients.

Topics: Adult; Aged; Calcium; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Vitamins

The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ.. One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education.. A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

Topics: Adolescent; Adult; Chronic Kidney Disease-Mineral and Bone Disorder; Contraindications; Female; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Oxalates; Renal Dialysis

A 39-year-old man with a 13-year history of hemodialysis was hospitalized with left back pain in May 1989. The plain radiograph showed a calcification in the left kidney. Ct scan demonstrated a round high density area. We could not exclude the possibility of malignancy, therefore, we performed left nephrectomy. Pathological examination revealed that a tumorous mass in the renal parenchyma and renal adenocarcinoma was confined to the mass intermingled with the deposition of the oxalate crystals. It was difficult to diagnose. Therefore we recommend nephrectomy when the diagnosis is uncertain.

Topics: Adenocarcinoma; Adult; Calcinosis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Renal Dialysis

A 23-year-old man with type 1 primary hyperoxaluria, renal failure, and oxalosis developed a severe cardiomyopathy while awaiting combined liver-kidney transplantation. This manifested as radiographic cardiomegaly, a dilated hypokinetic left ventricle with a decreased ejection fraction, ventricular arrhythmias, and cardiac uptake on bone scanning. On liver and kidney transplantation, these abnormalities markedly improved and/or reversed. The cardiac size almost normalized, the left ventricular ejection fraction increased from 20% to 34%, the ventricular arrhythmias resolved, and the cardiac uptake on bone scanning disappeared. This coincided with normalization of oxalate production and excretion. Severe cardiac involvement secondary to oxalosis in patients with primary hyperoxaluria may improve or reverse with combined liver-kidney transplantation.

Topics: Adult; Cardiomyopathies; Humans; Hyperoxaluria; Kidney Failure, Chronic; Kidney Transplantation; Liver; Liver Transplantation; Male; Oxalates; Postoperative Period; Radiography; Renal Dialysis

The diagnosis of primary hyperoxaluria in young children is hampered by the lack of a reliable reference range for urinary oxalate excretion, especially in infants. We present data on urinary oxalate and glycolate excretion in 137 normal children, on the plasma oxalate concentration in 33 normal children and 53 with chronic renal failure, and on amniotic fluid oxalate concentration in 63 uncomplicated pregnancies. The urinary oxalate:creatinine molar ratios were log normally distributed: mean (range) values were less than 1 year 0.061 (0.015-0.26), 1-5 years 0.036 (0.011-0.12), 5-12 years 0.030 (0.0059-0.15), and greater than 12 years 0.013 (0.0021-0.083). Geometric mean (range) plasma oxalate concentration in the normal children was 1.53 (0.78-3.02) mumols/l and was independent of age. The mean (SD) plasma oxalate: creatinine molar ratio in these normal children and 50 with chronic renal failure was 0.033 (0.013), and was independent of age and renal function. Mean (SD) amniotic fluid oxalate concentration was 19.0 (4.3) mumols/l.

Topics: Adolescent; Amniotic Fluid; Child; Child, Preschool; Creatine; Female; Glycolates; Humans; Hyperoxaluria, Primary; Infant; Kidney Failure, Chronic; Oxalates; Pregnancy; Reference Standards

This study was carried out in order to investigate renal oxalate excretion in a group of normal subjects (n = 40), a group of patients with uremia (n = 52) and a group with nephrolithiasis (n = 34). We found that the mean concentrations of oxalate in the 24-hour urine specimens of both patient groups were below the normal range. Although the renal creatinine clearance (CCR) was significantly decreased in some stone patients (n = 14), decreased renal oxalate clearance was noted only in those patients with severe renal failure. Thus, plasma oxalate was found to be elevated only in patients with chronic renal failure (mean +/- SD, 49.7 +/- 12.4 mumol/l), while the normal value was 17.0 +/- 6.7 mumol/l. The mean tubular excretion fraction of oxalate was also found to increase markedly in uremia with a mean of 26.3 +/- 17.3% (in normal subjects, 11.7 +/- 7.5%), but their mean daily urinary excretion of oxalate decreased to 63.2 mumol/day (mean value of 232.6 mumol/day in normal subjects). A positive correlation was observed between oxalate and creatinine, and between oxalate and calcium excretion, which was not found in normal subjects or patients with kidney stones. In nephrolithiasic patients, the daily excretion of oxalate, calcium and phosphate had no discernible increment and the mean excretory ratio of oxalate, calcium or phosphate to creatinine was all within normal limits. But when the CCR of stone patients was below 80 ml/min, their daily excretion of oxalate and calcium decreased significantly (p less than 0.01) and the excretory ratio of phosphate to creatinine markedly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Calcium; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Oxalates; Oxalic Acid

Topics: Humans; Kidney; Kidney Failure, Chronic; Oxalates; Oxalic Acid

The present study was undertaken to evaluate three factors which may contribute to the myocardial deposition of calcium oxalate in 5/6 nephrectomised rats: (1) increased plasma oxalate, (2) elevated plasma ionised calcium, and (3) local myocardial tissue damage. A simple increase in plasma oxalate concentrations produced by injection of sodium oxalate did not cause deposits in the heart. Increased plasma ionised calcium combined with elevated plasma oxalate for 60 days was likewise unimportant with regard to cardiac deposits. However, when local tissue damage was added by heterotopic cardiac transplantation, deposition of crystals was seen in four or five allografts damaged by rejection. In this model the rat's own heart was not affected. Although an increase in plasma oxalate values is not without significance, the present findings suggest that local tissue damage is a more important factor in the myocardial deposition of oxalate crystals in renal failure.

Topics: Animals; Creatinine; Crystallization; Heart Transplantation; Kidney Failure, Chronic; Myocardium; Nephrectomy; Oxalates; Rats; Rats, Inbred Strains

An ion chromatographic procedure for the determination of plasma oxalate is proposed, in which the ultrafiltered sample is injected into an ion-chromatographic system. Sample processing appears effective in avoiding spontaneous oxalogenesis. Sensitivity (down to 1.0 mumol/l) allows determinations in normal and pathological samples; recoveries from plasma ultrafiltration are 94.6 +/- 11.7%. Protein binding was investigated and precautions to improve recoveries from plasma ultrafiltration are proposed. The technique is simple to perform from healthy controls averaged 6.75 +/- 2.62 mumols/l (mean +/- S.D. n = 18); samples from patients with primary hyperoxaluria and chronic renal failure undergoing regular dialysis were also analysed and some of the data obtained are reported and discussed.

Topics: Adult; Ascorbic Acid; Chromatography, Ion Exchange; Glyoxylates; Humans; Hyperoxaluria; Indicators and Reagents; Kidney Failure, Chronic; Oxalates; Reference Values; Ultrafiltration

Topics: Biopsy; Granuloma; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Renal Dialysis; Skin Diseases

Kidneys removed from 58 pediatric patients at renal transplantation (except 3 cases), who had developed chronic renal failure and were maintained on dialysis, were investigated histopathologically, and the clinical profiles were taken into account. The patients ranged in age from 2 to 24 years, with an average of 11.2 years. The duration of dialysis ranged from 0.5 to 63 months, with an average of 12.6 months. The kidneys, which were conventionally prepared for histological observation, were subjectively divided into three groups depending on the degree of remaining nephrons. Patients with completely atrophic type (type 1), incompletely atrophic type (type 2), and mixed type of atrophy and hypertrophy (type 3) had a duration of dialysis of 20.0, 12.3, 6.3 months, respectively (Type 1 greater than Type 3, P less than 0.01). A correlation between histology and function was demonstrated, since urinary output was more than 200 ml/day in most of the type 3 patients, and less than 20 ml/day in all of the patients with type 1. The findings suggest that the functioning nephrons that remained at the beginning of dialysis generally become atrophic within one year after the initiation of dialysis. The ratio of kidney weight to body weight showed a significant negative correlation with both the duration of dialysis and that of illness. The histopathological changes seen in kidneys of patients on dialysis were reviewed. The findings suggested that certain changes, unusual epithelial proliferations an oxalate deposition, are associated with persisting renal function rather than the duration of dialysis.

Topics: Adolescent; Adult; Body Weight; Cell Division; Child; Child, Preschool; Female; Humans; Hyperplasia; Kidney; Kidney Failure, Chronic; Male; Organ Size; Oxalates; Oxalic Acid; Renal Dialysis; Time Factors; Urination

Plasma oxalate and erythrocyte glutamic oxaloacetate transaminase activity (EGOT) (an indicator of nutritional status with respect to pyridoxine) were measured in 21 patients maintained on regular continuous ambulatory peritoneal dialysis or haemodialysis before and after a 4-month period of supplementation with pyridoxine, 100 mg day-1. Prior to supplementation 10/21 patients showed subnormal EGOT activity, although the increment in activity on addition of pyridoxal-5-phosphate in vitro was within the normal range in all cases. Mean plasma oxalate was 31.5 mumol l-1 (SEM 2.9) prior to supplementation and did not change significantly with supplementation, despite normalization of EGOT activity in all but 2/21 patients. We conclude that pyridoxine deficiency does not contribute significantly to hyperoxalaemia in patients receiving dialysis and that 100 mg of pyridoxine daily is insufficient to reduce oxalate generation by a pharmacological action on glycine transamination.

Topics: Aspartate Aminotransferases; Erythrocytes; Humans; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Renal Dialysis; Vitamin B 6 Deficiency

The difficulties of biochemical diagnosis in children and in chronic renal failure are discussed in detail, as well as the development of diagnostic and therapeutic possibilities in recent years, exemplified by 4 cases. Excretion of oxalate (and glycolate) may be incorrectly assumed to be normal with: a) uncritical application of the method of measurement, b) disregard of the clearly lower oxalate excretion in children (values should be referred to m2 of body surface), c) disregard of a decreased glomerular filtration rate (values should be referred to the creatinine clearance). With compromised renal function the excretion of oxalate and glycolate in primary oxalosis drops to "normal" whereas plasma values increase considerably. In this case the biochemical diagnosis is possible only by measurement of plasma values of glycolate and oxalate. Consequently, extensive extrarenal deposition of calcium oxalate crystals will, as a rule, become clinically manifest only after chronic renal failure has turned irreversible. In recent years, several therapeutic procedures, have been developed. They are of therapeutic significance for the early stages of the disease as well. Observing especially conditions renal transplantation or combined hepatorenal transplantation can be managed with a successful outcome. As the perioxisomal enzyme is activated only in the liver cells, an early liver transplantation as a definitive treatment by enzyme replacement may be the successful therapy in the future.

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Calculi; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Oxalates; Oxalic Acid; Renal Dialysis; Urogenital System

Topics: Female; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney; Kidney Calculi; Kidney Failure, Chronic; Middle Aged; Oxalates; Skin; Skin Diseases; Vascular Diseases

Topics: Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Oxalates

We have previously reported that hyperoxalemia can be aggravated by vitamin C supplementation in regular hemodialysis patients. The present study was undertaken to examine the validity of this observation in an experimental setting. Fifty five-sixths nephrectomized rats were divided into two groups: 30 rats were allowed free access to water containing 8 mg/ml of vitamin C (100-160 mg/100 g/24 h) and the remainder given tap water without vitamin C. The serum creatinine increased and the Hct decreased gradually; however, there was no difference between the two groups. Plasma vitamin C, oxalate and urinary oxalate levels were higher in the vitamin -treated group than the nontreated rats. Histological examination revealed glomerular and interstitial fibrosis and round cell infiltration as well as tubular cyst formation. Oxalate deposits in renal tubules were found only in vitamin C-treated rats with advanced renal failure. Nontreated animals with equally advanced renal impairment showed no oxalate deposits. These results confirm our previous clinical findings that vitamin C supplementation aggravates the secondary oxalosis of chronic renal failure.

Topics: Animals; Ascorbic Acid; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Tubules; Male; Nephrectomy; Oxalates; Oxalic Acid; Rats; Rats, Inbred Strains

Plasma oxalate concentration was measured using an enzyme/bioluminescent assay in 289 patients (178 males, 111 females) with chronic renal failure (plasma creatinine greater than 200 mumol/l), age (SD) 55.5 (13.8) years. Plasma oxalate ranged between less than 0.8 and 48 mumol/l and showed a positive correlation with plasma creatinine (r = 0.57, p less than 0.0001). The slope of the regression line in 55 patients with glomerulonephritis (GN) was significantly lower than in patients with tubulointerstitial disease (TI); however the intercept was significantly higher in GN than in TI. Analysis of covariance showed no relationship between plasma oxalate concentration and age, duration of renal impairment, or administration of diuretics, vitamin D analogues, or phosphate binders. Longitudinal analysis of plasma oxalate measured 3-monthly in selected patients showed marked variability of oxalate/creatinine and oxalate/urea ratios.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Creatinine; Cross-Sectional Studies; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Nephritis, Interstitial; Oxalates; Regression Analysis

The present study was undertaken to evaluate the effects of vitamin C supplementation (VC-S) on the morbidity and mortality of 61 clinically stable outpatients maintained on regular hemodialysis (HD). All patients were given vitamin C (500 mg daily) for 2 years and observed for a further 2 years on no treatment. VC-S significantly increased the plasma levels of ascorbic acid up to 7.8 mg/dl (mean 3.3 +/- 0.4 s.e.m.) which fell after withdrawal to the normal range (mean 1.2 +/- 0.2 mg/dl). Hyperoxalemia was aggravated by VC-S (mean 61.5 +/- 3.3 mumol/l, range 33.3 to 165.5) while plasma oxalate levels in the unsupplemented period decreased to 36.3 +/- 3.3 mumol/l (p less than 0.01). There were no differences in creatinine, hematocrit, blood transfusion requirement, morbidity (including hospitalization) or mortality between the two periods of time in the same patients. In conclusion, we could not find any beneficial effects on morbidity or mortality as a result of using VC-S in regular HD patients. However, secondary hyperoxalemia was aggravated. As a result of these observations it appears that VC-S is harmful and unnecessary in these patients provided they are on an adequate diet.

Topics: Ascorbic Acid; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Renal Dialysis; Time Factors

The present study was undertaken to see if the oxalate deposits seen in renal tubules are a causative factor in the development of acquired renal cysts in chronic renal failure. Thirty 5/6 nephrectomized rats had free access to water containing 8 mg/ml of vitamin C (oxalate precursor) and 20 5/6 nephrectomized rats were given tap water without vitamin C. Oxalate deposits were found on microscopy in the renal tubules of vitamin C-treated rats in the 11th and 12th postnephrectomy months; however, acquired renal cysts were noted far in advance of the appearance of oxalate crystals. It has been suggested that the tubular dilatation seen in 5/6 nephrectomized rats is caused by an abrupt decrease in the functioning renal mass, leading to the production of a so-called 'renotropic factor'. However, oxalate deposits and renal tubular dilatation in oxalate-treated 5/6 nephrectomized rats preceded the renal tubular dilatation of untreated partially nephrectomized rats. In addition, these histological changes in the kidney were also seen in healthy rats which were given oxalate orally and subcutaneously. The present study suggested that the pathogenesis of acquired renal cysts is multifactorial. Renotropic factor may play an important role leading to nephron hyperplasia, but oxalate deposits in the renal tubules seem to be an important factor in the formation of these cysts.

Topics: Animals; Ascorbic Acid; Creatinine; Growth Substances; Histocytochemistry; Intercellular Signaling Peptides and Proteins; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Tubules; Nephrectomy; Oxalates; Rats; Rats, Inbred Strains

Oxalate metabolism was studied in ten patients with end-stage renal disease. No patient with primary hyperoxaluria was included in this study. Five patients were on regular haemodialysis and five patients were on chronic ambulatory peritoneal dialysis (CAPD). Oxalate metabolism was assessed by measurement of plasma oxalate concentration (POx), oxalate metabolic pool size (OxMP), tissue oxalate accumulation rate (TOxA), oxalate production rate (OxPR) and dialysis clearance of oxalate (DCOx). These observations were made on three separate occasions in each of the ten patients: initially when the patients were taking a routine ascorbic acid supplement of 100 mg per day; then after a period of 1 month with no ascorbic acid supplement; and then finally after a further period of 1 month's treatment with pyridoxine 800 mg daily. The values for POx, OxMP and TOxA were significantly increased in all ten patients and in the range observed in some patients with type I primary hyperoxaluria. There was no significant difference between immediate prehaemodialysis POx and the POx in the CAPD patients. The DCOx was very much greater during haemodialysis (mean 85 ml/min) than during CAPD (mean 8 ml/min). The acute fall in POx during haemodialysis was greater than 50% of the immediate pre-haemodialysis concentration. Ascorbic acid in a dose of 100 mg/day had no significant effect on the parameters of oxalate metabolism studied. Pyridoxine in a dose of 800 mg/day produced a significant fall in POx in both haemodialysis and CAPD patients.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Renal Dialysis

To examine the association between hyperoxalaemia and secondary oxalosis, measurement of plasma oxalate concentration was combined with a search for tissue deposition of calcium oxalate crystals in patients with chronic renal disease. Two groups of patients were studied. In the first, samples of the inferior epigastric artery were taken from 35 patients at the time of renal transplantation. In the second, sections taken at necropsy from 23 patients with chronic renal failure in whom plasma oxalate had been measured before death were examined. Though plasma oxalate concentrations ranged between 6 and 116 mumol/l (four to 78 times greater than the upper limit of the reference range), no extrarenal deposits of oxalate were found in either study. Renal deposition of oxalate was associated with a plasma oxalate concentration of greater than 20 mumol/l. This study gives no support to the suggestion that hyperoxalaemia of the degree seen in patients with the type of chronic renal failure that is not due to primary hyperoxaluria confers an appreciable risk of extrarenal oxalosis.

Topics: Adolescent; Adult; Calcium Oxalate; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Oxalates

Topics: Humans; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Reference Values

The factors involved in choosing a treatment modality for the infant, child and adolescent with endstage renal disease (ESRD) are different than those utilized when counseling an adult patient. Age at the time ESRD develops, mental status, psychosocial status and the primary renal disease must be taken into consideration when contemplating the optimal therapeutic modality for the pediatric patient with ESRD.

Topics: Adolescent; Age Factors; Anorexia; Bone Diseases; Child; Child, Preschool; Cystinosis; Glomerulosclerosis, Focal Segmental; Growth Disorders; Humans; Infant; Kidney Failure, Chronic; Kidney Transplantation; Oxalates; Oxalic Acid; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Psychology; Wilms Tumor

In order to separate the effect of oxalate retention in primary hyperoxaluria with renal failure from that of excessive oxalate synthesis and to determine the optimum time for renal transplantation in primary hyperoxaluria, we have studied a series of patients with different degrees of renal failure due to other causes. The results were compared with those obtained in studies on 8 patients with primary hyperoxaluria at different levels of residual overall renal function. In the patients with renal failure unrelated to primary hyperoxaluria, oxalate retention increases rapidly when the glomerular filtration rate (GFR) decreases below about 20 ml X min-1. These results suggest that the reduced renal excretory contribution to oxalate accumulation in primary hyperoxaluria would be expected to be particularly important in this range of GFR. In primary hyperoxaluria, oxalate retention occurs when GFR is only a little below the reference range and measures to remove oxalate from the body should be considered when the GFR falls below 40 ml X min-1 X 1.73 m-2, with a view to their introduction when the GFR is in the range 20-25 ml X min-1 X 1.73 m-2.

Topics: Carbon Radioisotopes; Glomerular Filtration Rate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Organometallic Compounds; Oxalates; Pentetic Acid; Renal Dialysis; Technetium Tc 99m Pentetate

Serum oxalate is easily controlled in patients with chronic renal failure not yet on dialysis by dietary protein restriction but poorly controlled by both haemodialysis and continuous ambulatory peritoneal dialysis (CAPD). In the control of serum oxalate in chronic renal failure dietary protein restriction is effective in the pre-dialysis patient whereas both CAPD and haemodialysis are relatively inefficient in end-stage renal failure.

Topics: Adult; Aged; Creatinine; Dietary Proteins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Primary oxalosis is a rare congenital disorder. The excessive oxalate biosynthesis induces deposits in many organs, particularly in kidney and bone. The late onset of primary oxalosis is reported in a 50-year-old man. His chronic renal failure was treated by maintenance hemodialysis for 3 years. He then developed a diffuse bone disease with osteosclerosis and roentgenographic features of hyperparathyroidism. A parathyroidectomy was performed, with debatable improvement of bone lesions. Laboratory results and histologic and histomorphometric studies before and after parathyroidectomy suggest a double histopathogenetic mechanism for this bone disease: renal osteodystrophy and massive bone oxalate deposits. Such deposits may induce both a heterogeneous osteosclerosis with dense metaphyseal bands and histologic bone lesions similar to those of hyperparathyroidism. The crystalline deposits induce in the bone tissue a granulomatous macrophagic reaction. These macrophages are unable to phagocytize the crystals and may be involved in active bone resorption. Bone lesions of oxalosis occur in patients with chronic renal failure, and hyperparathyroidism has a worsening role.

Topics: Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Macrophages; Male; Middle Aged; Oxalates

A patient with quiescent rheumatoid arthritis, amyloidosis and chronic renal failure developed an inflamed knee. Intracellular bipyramidal crystals characteristic of oxalate were found and are suggested as the cause of the acute arthritis. Since the patient had been treated with vitamin C, this precursor of oxalate is proposed as a possible factor in the crystal deposition.

Topics: Amyloidosis; Arthritis, Rheumatoid; Ascorbic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Peritoneal Dialysis; Radiography; Synovial Fluid

Topics: Adult; Ascorbic Acid; Calcinosis; Calcium Oxalate; Cardiomyopathies; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Oxalate (Ox), an end product of amino acid metabolism, accumulates in CRF patients as calcium crystal deposits in many soft tissues such as myocardium, kidney interstitium, etc. Since BF employs AN69, a high efficiency membrane, we tested its depurative efficacy for Ox against a hollow-fiber cuprophan dialyzer. Five CRF patients previously in HD and after six months of BF were studied. End-dialysis and pre-dialysis Ox values and dialyzer clearance were obtained. Predialysis Ox values were: 0.44 +/- 0.15 mg/dl in HD and 0.42 +/- 0.09 mg/dl in BF (NS). End-dialysis Ox values were: 0.30 +/- 0.09 mg/dl in HD and 0.22 +/- 0.04 mg/dl in BF (p less than 0.001). Pre and post dialysis values differed by 31% in HD and 47% in BF (p less than 0.001). Ox clearance was 98.8 +/- 10.3 ml/min in HD and 143 +/- 20.5 ml/min in BF. There was a rebound in Ox values at 48 hours (0.41 +/- 0.08 mg/dl in HD and 0.32 +/- 0.12 mg/dl in BF, (NS). These results indicate that Ox is depurated better during BF than during HD.

Topics: Acrylic Resins; Acrylonitrile; Blood; Creatinine; Humans; Kidney Failure, Chronic; Membranes, Artificial; Nitriles; Oxalates; Renal Dialysis; Ultrafiltration

Accumulation of oxalate, resulting in high plasma levels, is a common finding in end-stage renal disease. We investigated plasma concentration and peritoneal clearance of oxalate in 14 patients on continuous ambulatory peritoneal dialysis. The plasma oxalate levels in these patients (30.2 +/- 11.2 mumol/l) were as high as those in hemodialysis patients before dialysis (31.9 +/- 11.1 mumol/l). There was a significant correlation between plasma oxalate and urea nitrogen appearance (UNA). Dietary protein seems to be an important oxalate source in these patients, because the UNA reflects protein intake in stable patients. The mean peritoneal oxalate clearance was 6.64 +/- 1.56 l/day, close to the creatinine clearance. These results suggest that the plasma oxalate levels in CAPD patients may be sufficiently high to induce calcium oxalate deposition, and that methods of increasing oxalate removal and reducing oxalate burden are necessary for CAPD patients.

Topics: Adolescent; Adult; Aged; Blood Urea Nitrogen; Dietary Proteins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

In order to find out whether hyperoxaluria can be demonstrated in patients on chronic (twice a week) haemodialysis, a group of 13 patients was investigated. These included one patient with proven primary hyperoxaluria, one suspected of having this disease and 11 patients in whom no information was available as to their oxalate metabolism. Oxalate concentrations in haemodialysate fractions and blood samples, taken before and after dialysis, were determined. The patient with primary hyperoxaluria had a plasma oxalate concentration before dialysis above 100 mumol/l and after dialysis above 25 mumol/l, while the oxalate concentration in haemodialysate at the start of dialysis was above 25 mumol/l and at the end above 10 mumol/l. The patient suspected of hyperoxaluria had similar values. Of the remaining 11 patients, one was shown to exhibit a transient hyperoxaluria, but the others showed a normal oxalate metabolism. A plasma oxalate/creatinine concentration ratio exceeding 0.1, and the calculated total quantity of oxalate removed by dialysis exceeding 2 mmol, also enabled a diagnosis of hyperoxaluria to be made. Hyperoxaluria can still be demonstrated in patients, who because of renal failure are subjected to haemodialysis. Measurements of oxalate in haemodialysate and plasma are valuable in cases where kidney transplantations are considered, especially when the particular patient exhibits hyperoxaluria.

Topics: Adolescent; Adult; Aged; Chromatography, Gas; Female; Humans; Kidney Failure, Chronic; Male; Mass Spectrometry; Middle Aged; Oxalates; Renal Dialysis

Serum oxalate rises in uremia because of decreased renal clearance, and crystals of calcium oxalate occur in the tissues of uremic patients. Crystal formation suggests that either uremic serum is supersaturated with calcium oxalate, or local oxalate production or accumulation causes regional supersaturation. To test the first alternative, we ultrafiltered uremic serum and measured supersaturation with two different methods previously used to study supersaturation in urine. First, the relative saturation ratio (RSR), the ratio of the dissolved calcium oxalate complex to the thermodynamic calcium oxalate solubility product, was estimated for 11 uremic (before and after dialysis) and 4 normal serum samples using a computer program. Mean ultrafiltrate oxalate predialysis was 89 +/- 8 microM/liter (+/- SEM), 31 +/- 4 postdialysis, and 10 +/- 3 in normals. Mean RSR was 1.7 +/- 0.1 (predialysis), 0.7 +/- 0.1 (postdialysis), and 0.2 +/- 0.1 (normal), where values greater than 1 denote supersaturation, less than 1, undersaturation. Second, the concentration product ratio (CPR), the ratio of the measured calcium oxalate concentration product before to that after incubation of the sample with calcium oxalate monohydrate crystal, was measured in seven uremic and seven normal serum ultrafiltrates. Mean oxalate was 91 +/- 11 (uremic) and 8 +/- 3 (normal). Mean CPR was 1.4 +/- 0.2 (uremic) and 0.2 +/- 0.1 (normal). Predialysis, 17 of 18 uremic ultrafiltrates were supersaturated with respect to calcium oxalate. The degree of supersaturation was correlated with ultrafiltrate oxalate (RSR, r = 0.99, r = 29, P less than 0.001; CPR, r = 0.75, n = 11, P less than 0.001). A value of ultrafiltrate oxalate of 50 microM/liter separated undersaturated from supersaturated samples and occurred at a creatinine of approximately 9.0 mg/dl.

Topics: Adult; Aged; Calcium Oxalate; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Renal Dialysis

A continuous flow assay using immobilised oxalate oxidase was used to measure the level of oxalate in plasma ultrafiltrate obtained from healthy subjects and from patients with chronic renal failure. The levels of oxalate in plasma from normal subjects ranged from 1.3-3.1 mumol/l (mean 2.03; SD = 0.52) with females showing a higher (p less than 0.05) level (mean 2.25 mumol/l) than males (mean 1.87 mumol/l). The mean oxalate/creatinine clearance ratio in fourteen healthy subjects was greater than unity, thus indicating a net tubular secretion of oxalate. At physiological pH, L-ascorbate was converted to oxalate in whole blood following venepuncture, in plasma and in plasma ultrafiltrate. Reduction of the spontaneous generation of oxalate in the samples prior to analysis was achieved by acidification and treatment with sodium nitrite. A linear correlation (r = 0.92; p less than 0.001) was found between plasma oxalate and plasma creatinine in patients with chronic renal failure.

Topics: Adult; Ascorbic Acid; Creatinine; Enzymes, Immobilized; Female; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Oxidoreductases; Reference Values; Sex Factors; Sodium Nitrite; Ultrafiltration

Calcium oxalate crystals stain with alizarin red S at a pH of 7.0 but not at a pH of 4.2. In contrast, calcium phosphate and calcium carbonate stain at a pH of both 7.0 and 4.2. This difference allows presumptive identification of calcium oxalate deposits. The identity of calcium oxalate can then be confirmed by its insolubility in 2M acetic acid, since both calcium carbonate and calcium phosphate are soluble. We have applied this procedure for several years and have found it to be a rapid, reliable, and technically simple procedure for distinguishing calcium oxalate from other calcium deposits.

Topics: Animals; Anthraquinones; Calcium Carbonate; Calcium Oxalate; Calcium Phosphates; Ethylene Glycol; Ethylene Glycols; Histocytochemistry; Humans; Hydrogen-Ion Concentration; Kidney; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Rats; Rats, Inbred Strains; Solubility; Staining and Labeling

The mean plasma oxalic acid level is increased in renal failure. The mean plasma oxalic acid level was 74.8 +/- 18.5 mumol/l in 15 patients with chronic renal failure and 129.9 +/- 47.7 mumol/l in 31 patients on chronic haemodialysis which are several times higher than the normal range (16.8 +/- 6.0 mumol/l). During haemodialysis oxalic acid showed a behaviour similar to that of creatinine. The increased plasma oxalic acid levels are due to the accumulation of oxalic acid in renal insufficiency and additional metabolic factors increasing endogenous synthesis of oxalic acid. The administration of pyridoxine caused a decrease of the mean plasma oxalic acid level by 46% (32.0 to 56.1%) in 6 out of 8 chronic haemodialysis patients. This occurred most probably by correcting a vitamin B6 deficiency. Investigations of the intraerythrocyte glutamic oxalacetic transaminases showed, that the action of pyridoxine therapy on the endogenous oxalic acid synthesis can be explained by an increase of available pyridoxal-5-phosphate, the active metabolite of vitamin B6. The administration of vitamin B1, however, caused no statistically significant decrease of the plasma oxalic acid levels. Other influences on plasma oxalic acid synthesis result from the diminished excretion of the precursors of oxalic acid glycolic acid and ascorbic acid. The conversion of glycolic acid to glycine is probably increased in uraemia. The administration of 1 g ascorbic acid after each haemodialysis caused a striking increase of the plasma oxalic acid levels up to 240% of the initial value within 2 weeks, as a consequence of an increased metabolism of accumulated ascorbic acid. Increased plasma oxalic acid levels seem to be an important factor for calcium oxalate deposits in uraemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascorbic Acid; Aspartate Aminotransferases; Combined Modality Therapy; Erythrocytes; Glycolates; Humans; Kidney Failure, Chronic; Kidney Function Tests; Oxalates; Oxalic Acid; Pyridoxine; Renal Dialysis; Thiamine; Uremia

Topics: Adult; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Renal Dialysis

We studied vitamin C levels in 25 stable patients on chronic hemodialysis who were taking 0.5-1 g vitamin C orally daily and/or dialyzed against dialysate containing 33.3 micrograms/ml of vitamin C. We also studied the relationship between serum vitamin C and oxalate levels in 7 patients on chronic hemodialysis. All patients had markedly elevated pre- and postdialysis levels of vitamin C. The predialysis levels of vitamin C showed extremely good correlation to the serum oxalate levels. Overingestion of vitamin C in food or as supplementation may lead to excessive serum levels of vitamin C, resulting in hyperoxalemia that may contribute to vascular disease in patients on chronic hemodialysis.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Child; Humans; Kidney Failure, Chronic; Middle Aged; Oxalates; Oxalic Acid; Renal Dialysis

This paper dealt with the case of a 53 years old man, affected by a chronic renal failure as the initial symptom of a primary oxalosis and treated by hemodialysis three years ago. Two years after the onset of renal failure, the left knee was painful and swollen but no cartilage or bone joint lesion was observed. Presence of intra synovial calcium oxalate crystals suggests that this arthropathy may be related to the primary oxalosis. However the role of other calcium salts under identification evidenced by synovial electron microscopy (apatite ? pyrophosphate ?) is discussed.

Topics: Calcium Oxalate; Humans; Joint Diseases; Kidney Failure, Chronic; Knee Joint; Male; Middle Aged; Oxalates; Renal Dialysis; Synovial Membrane

Topics: Child; Eye; Eye Diseases; Humans; Kidney Failure, Chronic; Male; Oxalates; Renal Dialysis

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Kidney Failure, Chronic; Male; Oxalates

Measurement of oxalate levels in 14 patients with chronic renal failure, treated by maintenance hemodialysis, revealed elevated plasma oxalate concentrations in all patients 1,075.7 +/- (SEM) 253 micrograms/dl. In 7 of these subjects the oxalate concentration was more than three times higher than the upper limit of normal. Furthermore, a strong positive correlation (r = 0.75) between serum creatinine and plasma oxalate concentration was found. A combination of hemodialysis and hemoperfusion procedure was carried out in a dialysis patient with primary oxalosis as a cause of renal failure. The average oxalate clearance of the hemodialyzer during seven hemodialysis/hemoperfusion procedures was 91 ml/min and that of the charcoal detoxifier was 24 ml/min. The amount of oxalate removed during 4 1/2 h of the hemodialysis/hemoperfusion procedure was 429 mg. This amount was calculated to be produced in about 87 h, with an oxalate generation rate of 4.9 mg/h.

Topics: Adult; Creatinine; Female; Hemoperfusion; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis; Urea

We have measured the plasma oxalate concentration (POx), urinary oxalate excretion (UOx), oxalate equilibrium distribution volume (ODV), oxalate metabolic pool size [(ODV) X (POx)], total plasma oxalate clearance (PCOx), renal (or dialyser) oxalate clearance (RCOx), non-renal oxalate clearance (NRCOx) and the tissue oxalate accretion rate (TOA) = [(NRCOx) X (POx)] in three patients with severe renal failure due to primary hyperoxaluria who were being treated by peritoneal dialysis or haemodialysis, or by renal transplantation. The clearance (either GFR or dialyser) of [99mTc]diethylenetriaminepenta-acetate (DTPA) and the extracellular fluid volume (ECF) measured as [99mTc]DTPA distribution volume were also determined. Negligible amounts of 14C were found in faeces or as 14CO2 in expired air and hence (NRCOx) = (PCOx-RCOx). Haemodialysis removed oxalate more efficiently than peritoneal dialysis in the patient where a direct comparison was possible. Neither treatment could keep up with the TOA when performed for clinically acceptable times. The plasma oxalate concentrations calculated from 14C clearance through the dialyser and the chemically determined concentration of the oxalate in the dialysate were in the range 111-146 mumol/l. This is higher than in normals and in hyperoxaluric patients who are not in renal failure. Hence, although the ODV and ECF are similar to those of hyperoxaluric patients without renal failure and normal control subjects, the oxalate metabolic pool (ODV X POx) is grossly enlarged. In the patient treated by renal transplantation, the oxalate pool size diminished concurrently with the resumption of oxalate excretion but expanded again as renal function decreased due to oxalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Child; Extracellular Space; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Pentetic Acid; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Technetium; Technetium Tc 99m Pentetate

Eleven patients, aged 6 months to 47 years, with renal failure due to primary oxalosis, received renal allografts and were followed for 1 to 9 years. A specialized strategy for medical management included intensive pre-transplant hemodialysis and post-transplant long-term diuresis, administration of neutral phosphate, Mg++, and pyridoxine. Seven of ten living-related (LRD) transplants have good renal function, six with no biopsy evidence of renal oxalate deposition at up to 7 years after transplant. Two LRD graft losses from recurrent oxalosis, accompanied by massive secondary oxalate deposits, occurred in patients following endstage renal failure for over 3 years. A third LRD graft loss occurred following long-term (6 month) peritoneal dialysis in an infant. One cadaver transplant recipient has survived with recurrent oxalosis and poor graft function for 9 years. It is possible to perform successful renal transplantation in small children and adults with primary oxalosis and to completely prevent the deposition of oxalate in the renal allograft. Renal transplantation, with a strict medical protocol, would appear to be the initial treatment of choice for renal failure due to primary oxalosis.

Topics: Adult; Biopsy; Calcium Oxalate; Child; Child, Preschool; Diuretics; Female; Humans; Infant; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Magnesium; Male; Metabolic Diseases; Middle Aged; Oxalates; Phosphates; Pyridoxine; Renal Dialysis

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Serum oxalic acid (sOx) was determined with a new, specific enzymatic method in 73 uremic patients and the values were plotted against serum creatinine. 41 patients received a free mixed diet, and 32 similar patients were given a low-nitrogen diet supplemented with essential amino acids, ketoanalogues, and calcium carbonate (AD). A significant correlation was found between serum creatinine and sOx levels in patients following a free mixed diet, while no correlation appeared in patients on AD: The sOx concentrations were significantly lower and even normal in this group, and a significant reduction of sOx occurred in 10 patients with chronic renal failure, who changed from a free mixed diet to the AD. The lowering of sOx concentration in patients following AD is attributed both to low intake of its metabolic precursors and to the oral calcium carbonate supplementation.

Topics: Amino Acids, Essential; Calcium Carbonate; Creatinine; Dietary Proteins; Female; Humans; Keto Acids; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid

Topics: Calcium Oxalate; Humans; Kidney; Kidney Failure, Chronic; Oxalates

Topics: Adolescent; Adult; Female; Humans; Kidney Failure, Chronic; Male; Metabolism, Inborn Errors; Oxalates

Two patients with documented primary hyperoxaluria have received renal allografts with successful function for 10 years and 25 months. The patient in case 1 required a ureterolithotomy 6 years post-transplantation to remove a renal calculus of calcium oxalate. This case illustrates that despite recurrence of oxalate stones in the allograft, satisfactory renal function can be maintained by careful follow-up and appropriate interventions. Factors that may be important in successful graft function include the occurrence of acute rejection episodes, avoidance of ischemic graft damage, trials of pyridoxine therapy to decrease oxalate excretion, and frequent evaluation with appropriate interventions as necessary. Renal transplantation is a suitable and possibly the preferred form of therapy of end stage renal disease in patients with primary hyperoxaluria.

Topics: Adult; Biopsy; Female; Follow-Up Studies; Graft Survival; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Kidney Transplantation; Oxalates; Oxalic Acid; Pyridoxine; Recurrence; Time Factors

Topics: Adult; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Oxalates; Prognosis; Pyridoxine

Topics: Adult; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Oxalates

The daily amount of oxalate in normales is formed by about 90 per cent from endogenous sources. Approximately 10 per cent are due to intestinal absorption of dietary oxalate. The oxalate formed endogenously is derived from aminoacid-, carbohydrate- and ascorbic acid metabolism. Oxalate synthesis is increased in inherited defects of enzymes (primary hyperoxaluria) or as a consequence of exogenous factors (vitamin-B6-deficiency, ethylene glycol intoxication, high dose ascorbic acid application, possibly excessive protein and carbohydrate intake). The intestinal absorption of oxalate is increased in some diseases of the intestinal tract (Morbus Crohn, ulcerative colitis). Oxalate, that is totally excreted in urine, is the principal component for urinary calcium oxalate saturation. Oxalate accumulates in renal failure. The increased plasma oxalate level - as a consequence of impaired renal function and additional metabolic influences - is an important factor for calcium oxalate depositions in uremic patients.

Topics: Animals; Humans; Kidney Failure, Chronic; Oxalates; Vitamin B 6 Deficiency; Xylitol

The use of new dialythic technics has increased the survival times for patients with primary hyperoxaluria. From here the possibility of visualizing X-rays signs specific of oxalosis besides the typical bone lesions of hyperparathyroidism secondary to chronic renal failure. Recent hysto-pathological studies allowed to correlate such radiological findings to a new pathogenetical mechanism that would be responsible of the bone lesion specific for oxalosis and that might be caused by the presence of reabsorption cavities made up by macrophagic cells fagocyting cristals.

Topics: Adolescent; Bone and Bones; Bone Diseases; Cartilage, Articular; Crystallization; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Male; Nephrocalcinosis; Oxalates; Radiography; Renal Dialysis; Urinary Calculi

Topics: Child, Preschool; Female; Fractures, Spontaneous; Growth Disorders; Humans; Hypercalcemia; Kidney Calculi; Kidney Failure, Chronic; Metabolism, Inborn Errors; Oxalates; Oxalic Acid

Topics: Adolescent; Bone Diseases; Femur; Humans; Kidney Calculi; Kidney Failure, Chronic; Male; Oxalates; Radiography; Renal Dialysis; Sclerosis

In eight chronic haemodialysed patients with secondary hyperoxalaemia due to renal insufficiency vitamin B6, an important co-enzyme in oxalic acid metabolism, was administered. Mean plasma oxalic acid values decreased from 149.5 +/- 67.0 mmol/L to 99.0 +/- 36.4 mmol/L within two weeks and to 93.8 +/- 33.1 mmol/L after four weeks of pyridoxine treatment (p less than 0.01, p less than 0.01). The mean reduction was 46 per cent (32.0 to 56.1). Patients with high pre-values of plasma oxalic acid had the most pronounced decrease. In order to prevent calcium oxalate deposition a reduction of plasma oxalic acid in patients on RDT seems to be an important goal in long term haemodialysis treatment.

Topics: Dose-Response Relationship, Drug; Humans; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Pyridoxine; Renal Dialysis; Time Factors

Topics: Calcium; Citrates; Humans; Kidney Failure, Chronic; Male; Oxalates; Paraplegia; Spinal Cord Injuries

The daily urinary excretion of oxalate has been found to be lower than normal in patients with renal failure and the decrease to be directly proportional to the impairment of renal function. It has also been found that the gut flora from uremic patients destroys oxalate 'in vitro' more efficiently than the gut flora from normal people. It is postulated that an adaptation occurs in the gut flora of uremics to 'metabolize' oxalate, and this enteric elimination may account for its decreased urinary excretion.

Topics: Humans; Kidney Failure, Chronic; Oxalates

Topics: Blood; Calcinosis; Calcium Oxalate; Creatinine; Humans; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Pyridoxine; Renal Dialysis; Ultrafiltration; Uremia

The concentration of oxalic acid was determined in the plasma of 15 patients with conservatively treated chronic renal insufficiency and 17 dialysis patients. A cumulation of oxalic acid was found in connection with uraemia. The extent to which plasma oxalic acid concentrations were raised depended on the degree of renal insufficiency and was directly related to the plasma creatinine values in all patients with or without dialysis. In the patients with chronic renal insufficiency the median plasma oxalic acid concentration was 74.4-18.5 (control group 27.0 +/- 7.4) mumol/l. In the dialysis patients the levels were even higher, at 137.5 +/- 56.0 mumol. By means of haemodialysis it was possible to lower the plasma oxalic levels by about the same amount as creatinine concentrations. The higher plasma oxalic acid concentrations seem to be an important pathogenetic factor in the formation of uraemic calcification in various organs. The therapeutic consequences are to increase the duration and frequency of dialysis and to remedy possible vitamin B6 deficiency.

Topics: Adult; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Renal Dialysis; Uremia

Topics: Amino Acid Metabolism, Inborn Errors; Bone Diseases, Metabolic; Child; Female; Glyoxylates; Humans; Kidney Failure, Chronic; Kidney Transplantation; Oxalates; Radiography; Transplantation, Homologous

The conduction system in 31 patients (average age 43 years) who died suddenly and unexpectedly is analyzed. Seven cases show essential lesions of the conduction tissue, these lesions being the only pathological findings at all in 5 cases. The loss of conducting fibers is severe and fulfills our morphological criteria for av-block (see Part I). Considering these lesions are the only pathologic findings, there is every reason to believe that these patients died of Adams-Stokes attacks. Lack of evidence of a basic disease means that there is idiopathic loss of conducting fibers. The site of the lesion is mainly the branching bundle and the origin of both bundle branches. Fibrosis is never a main feature, and this is why the author is reluctant to characterize the disease simply as bilateral bundle branch fibrosis.

Topics: Adult; Death, Sudden; Female; Heart Block; Heart Conduction System; Humans; Infant; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalates; Pacemaker, Artificial; Purkinje Fibers

Topics: Adult; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolism, Inborn Errors; Oxalates; Tissue Survival; Transplantation, Homologous

Topics: Aldehyde-Ketone Transferases; Calcinosis; Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Glyoxylates; Humans; Ketoglutaric Acids; Kidney Calculi; Kidney Failure, Chronic; Male; Oxalates; Oxo-Acid-Lyases

Topics: Humans; Kidney Failure, Chronic; Oxalates; Renal Dialysis

Topics: Humans; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Pyridoxine; Renal Dialysis; Transplantation, Homologous

Topics: Adolescent; Adult; Aged; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Myocardium; Oxalates; Renal Dialysis

The incidence and severity of oxalate deposition as a complication of chronic renal failure in a retrospective study of 73 patients is presented. The reason for this study was the occurrence of a syndrome characterised by multiple shunt-complications, muscle weakness and peripheral ulceration in three haemodialysis patients. This syndrome seems to be caused by an obliterative vasculitis due to oxalate deposition in the media of peripheral vessels (Figure 1).

Topics: Adult; Aged; Humans; Kidney; Kidney Failure, Chronic; Metabolic Diseases; Middle Aged; Myocardium; Nephrectomy; Oxalates; Renal Dialysis; Retrospective Studies

Livedo reticularis developed on the lower extremities of a 37-year-old woman with primary oxalosis and renal failure that was treated by hemodialysis. Biopsy results of the involved skin indicated oxalate crystals in the walls of the blood vessels of the dermis and subcutaneous tissue. Oxalosis with vascular involvement should be included in the long list of causes of livedo reticularis.

Topics: Adult; Female; Humans; Kidney Failure, Chronic; Oxalates; Prognosis; Renal Dialysis; Skin; Skin Diseases; Vascular Diseases

Direct tubular damage, hypersensitivity reaction, metabolically mediated kidney disturbances, and chronic nephropathies are important sequelae of several drugs or their metabolites. In this review the drug-induced kidney disease is discussed from a clinical, histological, and pathogenetic point of view. The knowledge of possible nephrotoxic reactions and their underlying toxins are essential for prevention of this kidney disease.

Topics: Analgesics; Drug Hypersensitivity; Ethylene Glycols; Glomerulonephritis; Humans; Hypercalcemia; Kidney Concentrating Ability; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubular Necrosis, Acute; Methicillin; Methotrexate; Nephritis, Interstitial; Oxalates

Topics: Creatinine; Humans; Kidney Failure, Chronic; Oxalates; Renal Dialysis

Topics: Humans; Kidney Failure, Chronic; Oxalates; Renal Dialysis; Urinary Calculi

An 18-year-old female with primary oxalosis, seen first when she was in advanced renal failure, developed a severe necrotizing angiopathy which began after a rapid decrease in renal function requiring chronic dialysis. Because of the severe angiopathy the preliminary diagnosis of an acute autoimmune vasculitis had been made. The correct diagnosis was revealed by renal biopsy and a renal transplantation performed. Soon after severe oxalosis led to failure of the renal transplant and death. The patient had also had familial spherocytosis, inherited from her father, while the oxalosis had been inherited from her mother. It is suggested that early transplantation at the onset of renal failure, as long as the blood oxalate level is still tolerably low, may give better results than have so far been reported.

Topics: Adolescent; Female; Humans; Kidney Calculi; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Spherocytosis, Hereditary; Vascular Diseases

Primary hyperoxaluria is a rare congenital disorder characterized by large quantities of urinary oxalate with resultant nephrocalcinosis and nephrolithiasis and by deposits of calcium oxalate in other organs. Renal failure occurs early in life. Reports of unsuccessful renal transplantation attempts in this disorder underscore the need for antemortem diagnosis. Percutaneous bone biopsy is a relatively new procedure that is easily done at bedside, safe, and of potentially high yield in the demonstration of tissue oxalate. Three cases presented here show the characteristic histologic picture seen in this disease. In one case, the diagnosis was established by bone biopsy.

Topics: Adolescent; Adult; Biopsy; Bone and Bones; Bone Marrow; Child; Female; Humans; Infant; Kidney Failure, Chronic; Male; Oxalates

1. Plasma oxalate has been measured by a radioisotopic method applicable to all concentrations of plasma oxalate and renal function, and also by an enzymatic method which was only applicable to raised concentrations of plasma oxalate. 2. Where the two methods could be applied simultaneously, the agreement between them was good. 3. Plasma oxalate was 86% ultrafiltrable at concentrations of up to 44 micromol/l. 4. Oxalate clearance and the exchangeable oxalate pool were also measured. The ratio of oxalate clearance to creatinine clearance was greater than unity in most normal subjects and patients. 5. These methods were used in normal subjects and in patients with primary hyperoxaluria and/or chronic renal failure. A raised plasma oxalate concentration was found in both conditions. Chronic renal failure is probably the most common cause of a raised plasma oxalate.

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Creatinine; Female; Humans; Kidney; Kidney Failure, Chronic; Oxalates

The pattern of the renal disease and the pathological changes were studied in the kidneys of 80 autopsied patients who were maintained on hemodialysis for periods of up to seven years. Chronic pyelonephritis was most frequently encountered (25%); next in frequency were chronic glomerulonephritis (17.5%) and nephrosclerosis (17.5%). Moderate to severe intrarenal vascular changes were seen; intimal changes were most prominent. Statistically significant differences were observed in the distribution of the initimal lesions in intrarenal vessels of different calibres. Deposits of oxalate crystals, usually in the renal tubules, were encountered in all kidneys except four. Twenty-four patients (30%) showed acquired cystic kidney disease; renal calcification was observed in 61 others. The pathogenesis of these lesions in hemodialysis kidneys and their clinical significance are discussed.

Topics: Adult; Aged; Histocytochemistry; Humans; Kidney; Kidney Diseases, Cystic; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Renal Artery; Renal Dialysis

The incidence and distribution of deposition of oxalate crystals were studied in various organs of 80 patients with chronic renal failure maintained on hemodialysis for periods ranging from three weeks to seven years. The most frequently involved organs were the kidneys, thyroid, and myocardium. Less prominent deposit was found in the spleen and the lungs. Moderate to severe renal oxalosis was encountered more frequently in patients maintained for longer periods on hemodialysis. The therapeutic implication of distinguishing secondary from primary oxalosis is stressed. The identification and the mechanism of deposition of oxalate in tissues are discussed.

Topics: Adolescent; Adult; Aged; Female; Histocytochemistry; Humans; Kidney; Kidney Failure, Chronic; Male; Metabolic Diseases; Middle Aged; Myocardium; Oxalates; Renal Dialysis; Thyroid Gland

Cadaver renal transplantation was performed in a 14-year-old girl with primary hyperoxaluria. Acute tubular necrosis was present initially, and a moderate rejection crisis occurred at 6 weeks. Renal biopsy performed at 4 months showed considerable deposition of calcium oxalate. Urinary excretion of oxalate varied between 315-371 mg/24 hr per 1.73 m2 (normal less than 50 mg). Despite these unfavourable factors, renal function has remained stable for the last 2 1/2 years; the serum creatinine is 1.5 mg/100 ml at 3 years. This is the longest surviving graft reported so far in documented primary hyperoxaluria. Graft failures in previous reports could in part be explained by additional complicating factors. It is concluded that renal transplantation is not necessarily contraindicated in primary hyperoxaluria.

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Creatinine; Female; Follow-Up Studies; Glycolates; Host vs Graft Reaction; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Oxalates; Renal Dialysis; Transplantation, Homologous

Topics: Amyloidosis; Bile Acids and Salts; Celiac Disease; Cholelithiasis; Cholestyramine Resin; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Diseases; Glycine; Hepatic Encephalopathy; Humans; Kidney Calculi; Kidney Diseases; Kidney Failure, Chronic; Malabsorption Syndromes; Oxalates; Proteinuria

Oxalosis, a rare metabolic disorder, leads to excessive formation of oxalate and deposition of calcium oxalate crystals in the tissue. This leads to renal insufficiency with resulting secondary hyperparathyroidism and myelofibrosis. In a 27 year old female patient, extensive destruction of the maxilla, mandible and teeth was observed which has not yet been described and which led to the loss of all teeth.

Topics: Adult; Alveolar Process; Bone Resorption; Humans; Hyperparathyroidism; Jaw Diseases; Kidney Calculi; Kidney Failure, Chronic; Metabolism, Inborn Errors; Oxalates; Tooth Mobility; Tooth Resorption; Tooth Root

A 45-year-old man underwent a jejunoileal shunt procedure for obesity. Twenty months later he developed severe oxalosis and chronic renal failure, which required maintenance hemodialysis. The sequential observation of two biopsy specimens and the necropsy (over a span of 39 months) suggests that oxalate deposition caused tubular obstruction and destruction with subsequent atrophy of nephrons. This indicates that patients undergoing intestinal bypass are at risk for developing irreversible renal failure due to enteric hyperoxaluria.

Topics: Humans; Ileum; Jejunum; Kidney Failure, Chronic; Kidney Tubules; Male; Metabolic Diseases; Middle Aged; Obesity; Oxalates; Postoperative Complications

A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis.

Topics: Brain; Crystallization; Female; Humans; Kidney Failure, Chronic; Meninges; Middle Aged; Oxalates

A 61 year old man had chronic renal failure because of oxaluria and renal calculi. Two years before death, while on hemodialysis, he developed severe progressive peripheral neuropathy. At autopsy calcium oxalate crystals were found in the peripheral nerves and other tissues. Nerve lesions included segmental demyelination, axonal degeneration and crystalline deposits within the myelin sheath. Ultrastructurally there were foci of osmiophilic granular material within myelin lamellae and endoneurium, and pleomorphic lamellar bodies in the perinuclear Schwann cell cytoplasm. It is probable that chronic hemodialysis favors the deposition of oxalate in the Schwann cells and the development of neuropathy in patients with primary hyperoxaluria and renal failure.

Topics: Demyelinating Diseases; Humans; Kidney Calculi; Kidney Failure, Chronic; Male; Median Nerve; Metabolic Diseases; Middle Aged; Nephrectomy; Nerve Fibers, Myelinated; Oxalates; Peripheral Nerves; Peripheral Nervous System Diseases; Radial Nerve; Renal Dialysis; Schwann Cells; Sciatic Nerve

A patient with chronic renal disease due to primary hyperoxaluria developed a rapidly progressing motor neuropathy with marked impairment of nerve conduction. Pathological studies demonstrated the presence of both axonal degeneration and segmental demyelination, together with the presence of oxalate crystals within axons. It is suggested that the development of peripheral neuropathy complicating hyperoxaluria is a consequence of the increased life-span mad possible by haemodialysis.

Topics: Adult; Carbohydrate Metabolism, Inborn Errors; Humans; Kidney Failure, Chronic; Male; Oxalates; Peripheral Nerves; Peripheral Nervous System Diseases; Syndrome

A 33 year old patient with primary oxalosis was submitted to cadaver kidney transplantation after 15 months treatment by hemodialysis. During the dialysis period, he developed complete heart block which immediately followed bilateral nephrectomy. The transplant functioned correctly and was found to excrete large amounts of oxalate. Death, which supervened 7 months after transplantation, was due to miliary tuberculosis. The patient's own kidneys and various organs examined post mortem showed extensive oxalate deposits, which were mainly observed in the graft, conducting system of the heart, ocular structures, spleen and pancreas. The problems of managing terminal uremia secondary to primary oxalosis are discussed.

Topics: Adult; Heart Block; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Nephrectomy; Oxalates; Renal Dialysis; Transplantation, Homologous

Topics: Adolescent; Adult; Amyloidosis; Child; Cystinosis; Diabetic Nephropathies; Fabry Disease; Female; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolic Diseases; Middle Aged; Nephritis; Nephritis, Hereditary; Oxalates; Renal Dialysis; Retrospective Studies; Transplantation, Homologous

Topics: Acidosis, Renal Tubular; Humans; Ileum; Jejunum; Kidney Diseases; Kidney Failure, Chronic; Nephritis, Interstitial; Obesity; Oxalates; Postoperative Complications; Renal Aminoacidurias

A presentation is given of the severe changes in the retina of a 26-year-old man caused by intraocular Calciumoxalate crystals with clinical, histological and polarizing optical findings. The stadia of the retinopathia oxalogenica are classified here.

Topics: Adult; Crystallization; Eye Manifestations; Histocytochemistry; Humans; Kidney Failure, Chronic; Male; Oxalates; Retina; Retinal Diseases

alpha-Chlorohydrin (I) is oxidatively metabolized to beta-chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of alpha-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.. The oxidative metabolism of alpha-chlorohydrin and the chemical indu ction of spermatocoeles are described. Alpha-chlorohydrin was oxidative ly metabolized to beta-chlorolactic acid and oxalic acid. Deposition of calcium oxalate within the renal tubules was responsible for the toxic effects of alpha-chlorohydrin and a similar action on the epididymis or epididymal blood vessels may initiate the formation of spermatocoeles from this and other male antifertility agents.

Topics: Animals; Anuria; Diuresis; Kidney Failure, Chronic; Kidney Tubules; Lactates; Male; Oxalates; Rats; Spermatocele

Oxalosis involving bone secondary to prolonged chronic renal failure and long-term dialysis occurred in a living patient. The cystalline deposit in the small fragment of bone was identified by electron diffraction.

Topics: Adult; Birefringence; Bone and Bones; Bone Diseases; Calcium; Female; Humans; Kidney Failure, Chronic; Microscopy, Electron; Oxalates

Calcium oxalate crystals were demonstrated in the retinal pigment epithelium (RPE) of a 66-year old white man with changes in the fundus oculi consistent with the flecked retina ayndrome. The patient had a history of rheumatoid arthritis, mild hypertension, and mild renal insufficiency presumed due to his hypertension. He underwent prolonged abdominal surgery under methoxyflurane anesthesia, following which he developed acute irreversible renal failure. Calcium oxalate crystals were demonstrated postoperatively in a kidney biopsy specimen. He subsequently was maintained on renal dialysis with decreasing renal function. Several weeks before his death fundus examination revealed a picture suggestive of a flecked retina syndrome. At autopsy, widespread oxalosis was found including crystals in the RPE and in some areas in the neural retina and cillary epithelium.

Topics: Acute Kidney Injury; Aged; Anesthesia; Autopsy; Biopsy; Calcium; Crystallization; Epithelium; Fundus Oculi; Humans; Kidney; Kidney Failure, Chronic; Male; Metabolic Diseases; Methoxyflurane; Oxalates; Retina; Retinal Diseases; Retinal Pigments; Syndrome

Of 125 patients with postsurgical acute tubular necrosis, 87 died, 34 regained clinical normal renal function, and 4 survivors (9.5%) were left with severe permanent renal failure, two of whom required chronic dialysis and transplantation. Preoperatively these 4 patients had normal renal function. The 4 patients were above age 60, two had undergone methoxyflurane anesthesia, and nephrotoxic antibiotics were used in all. The incidence of permanent renal failure is much higher than ever reported and may reflect the survival of patients who previously died because of less ideal dialysis. We believe that the cause of this permanent lesion is multifactorial, including age (over 60 years), nephrotoxic antibiotics (particularly cephalothin and gentamicin sulfate), and nephrotoxic anesthetic (methoxyflurane) agents. This combination of factors should be avoided whenever possible.

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Aged; Anesthetics; Anti-Bacterial Agents; Blood Urea Nitrogen; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Kidney Cortex; Kidney Failure, Chronic; Kidney Tubular Necrosis, Acute; Male; Methoxyflurane; Middle Aged; Oxalates; Postoperative Complications; Renal Dialysis; Sex Factors; Syndrome

An analysis is made of 100 school children with recurrent urolithiasis treated during the last six years. The clinical findings and prognosis in this patient material are outlined. The incidence of recurrence was 23.7% in 421 patients.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Cystine; Czechoslovakia; Female; Focal Infection; Humans; Kidney Failure, Chronic; Male; Metabolic Diseases; Oxalates; Phosphates; Recurrence; Sex Factors; Time Factors; Uric Acid; Urinary Calculi; Urinary Tract; Urinary Tract Infections

During the last six years 400 children with urolithiasis underwent a six weeks rehabilitation treatment in a specialized children's sanitorium for renal diseases. The clinical picture, course of the disease, etiology, complications and therapy are analyzed and discussed. Urolithiasis is surprisingly common in girls; it occurs commonly not until school age and recurrence occurs in one-fourth of the children. The importance of stone analysis for the therapy is outlined and the necessity of conservative renal surgery is emphasized.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Cystine; Female; Focal Infection; Humans; Infant; Kidney Failure, Chronic; Male; Metabolic Diseases; Nephrectomy; Oxalates; Phosphates; Recurrence; Sex Factors; Uric Acid; Urinary Calculi; Urinary Tract; Urinary Tract Infections

Topics: Adolescent; Adult; Alcohol Oxidoreductases; Biopsy; Bone and Bones; Carboxy-Lyases; Female; Glyceric Acids; Glycolates; Glyoxylates; Humans; Ketoglutaric Acids; Kidney; Kidney Calculi; Kidney Failure, Chronic; Kidney Tubules; Male; Metabolic Diseases; Methods; Microscopy, Polarization; Nephritis, Interstitial; Oxalates; Renal Artery Obstruction

Topics: Adult; Calcium; Humans; Ileum; Jejunum; Kidney; Kidney Failure, Chronic; Male; Nephrocalcinosis; Obesity; Oxalates; Postoperative Complications

Topics: Animals; Biological Transport, Active; Biotransformation; Bufo marinus; Depression, Chemical; Edetic Acid; Fluorides; Kidney Failure, Chronic; Methoxyflurane; Oxalates; Sodium; Stimulation, Chemical; Urinary Bladder; Urine

Topics: Adolescent; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Humerus; Hyperparathyroidism, Secondary; Infant; Kidney Failure, Chronic; Osteosclerosis; Oxalates; Radiography; Skull

Topics: Adolescent; Bone and Bones; Bone Diseases; Calcium; Female; Histocytochemistry; Humans; Kidney Failure, Chronic; Male; Metabolic Diseases; Oxalates

Topics: Adult; Autopsy; Biopsy; Cadaver; Creatinine; Female; Humans; Kidney Calculi; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Renal Dialysis; Transplantation, Homologous

Topics: Adult; Calcium; Glomerulonephritis; Humans; Kidney Calculi; Kidney Failure, Chronic; Male; Oxalates; Peritoneal Dialysis; Renal Dialysis

Topics: Adolescent; Adult; Aged; Cardiomyopathies; Child; Female; Heart Block; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardium; Oxalates

Topics: Humans; Kidney Calculi; Kidney Failure, Chronic; Oxalates

Topics: Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Oxalates; Renal Dialysis; Transplantation, Homologous

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Calcium; Child; Child, Preschool; Endomyocardial Fibrosis; Humans; Infant; Kidney; Kidney Failure, Chronic; Kidney Tubules; Metabolic Diseases; Middle Aged; Myocardium; Oxalates; Peritoneal Dialysis; Renal Dialysis; Spine; Splenic Artery; Uremia

Topics: Adult; Blood Urea Nitrogen; Bone and Bones; Cardiomyopathies; Female; Heart Block; Heart Conduction System; Heart Failure; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Metabolism, Inborn Errors; Myocardium; Nephrectomy; Oxalates; Pancreas; Renal Dialysis; Thyroid Gland

Topics: Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Nephrocalcinosis; Oxalates; Renal Dialysis; Transplantation, Homologous

Topics: Adolescent; Candidiasis; Digestive System; Glyoxylates; Heart Conduction System; Histocompatibility; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolism, Inborn Errors; Myocardium; Oxalates; Transplantation, Homologous; Uremia

Topics: Acidosis, Renal Tubular; Alcohol Oxidoreductases; Allopurinol; Biopsy; Blood Urea Nitrogen; Calcium Metabolism Disorders; Disulfiram; Enzyme Repression; Glyoxylates; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Leukocytes; Nephrocalcinosis; Oxalates; Pyridoxine

Topics: Child; Cyanates; Diet Therapy; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolism, Inborn Errors; Oxalates; Oxidoreductases; Pyridoxine; Transplantation, Homologous

Topics: Adult; Glomerulonephritis; Glyoxylates; Humans; In Vitro Techniques; Ketoglutaric Acids; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Ligases; Liver; Metabolism, Inborn Errors; Mitochondria; Oxalates; Pyelonephritis; Spleen; Thiamine Pyrophosphate

Topics: Chromatography, Gel; Creatine; Humans; Kidney Failure, Chronic; Oxalates; Renal Dialysis; Urea; Uric Acid

Topics: Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Nephrectomy; Oxalates; Oxalic Acid; Renal Insufficiency, Chronic