oxalates and Nephrocalcinosis

Hyperoxaluria is defined by an increase of urinary oxalate, leading to kidney stones, nephrocalcinosis and/or chronic kidney disease. There are different diseases related to hyperoxaluria: (1) kidney stones, 50% of them being explained by intermittent hyperoxaluria, secondary to dietary mistakes such as low hydration, excess of oxalate consumption and/or low calcium consumption; (2) primary hyperoxaluria, a genetic orphan disease inducing a massive production of oxalate by the liver, leading to increased plasma oxalate increase and saturation, and further systemic oxalosis with oxalate deposition, nephrocalcinosis and ultimately kidney failure, the management of this disease being currently dramatically modified by the onset of new therapeutic tools such as RNA interference; and (3) enteric hyperoxaluria, resulting from increased intestinal oxalate absorption because of intestinal malabsorption (short bowel syndrome, bariatric surgery, exocrine pancreatic insufficiency, etc.). Diagnosis and therapeutic management of these diseases require a full understanding of oxalate physiology that we detail in this review.. L’hyperoxalurie, définie par une élévation de l’oxalate urinaire, favorise la survenue d’une maladie lithiasique, d’une néphrocalcinose et/ou d’une insuffisance rénale chronique. L’hyperoxalurie peut témoigner de différentes maladies : (1) l’hyperoxalurie diététique, responsable de 50 % de la maladie lithiasique par le biais d’erreurs alimentaires (hydratation insuffisante, consommation excessive d’oxalate et/ou consommation insuffisante de calcium) ; (2) les hyperoxaluries primaires, maladies génétiques orphelines responsables d’une production massive d’oxalate aboutissant à des dépôts tissulaires précoces (dès l’enfance) et sévères (à l’origine d’une insuffisance rénale terminale puis d’une thésaurismose avec atteinte multiviscérale) et dont le pronostic est aujourd’hui transformé par les nouvelles thérapies (ARN interférents) ; (3) l’hyperoxalurie entérique, résultant d’une augmentation de l’absorption digestive de l’oxalate dans une situation de malabsorption (syndrome du grêle court, chirurgie bariatrique, insuffisance pancréatique exocrine, etc.). La physiologie de l’oxalate, détaillée dans cet article, permet d’appréhender la prise en charge diagnostique et thérapeutique de ces maladies.

Topics: Humans; Hyperoxaluria; Intestinal Absorption; Kidney Calculi; Nephrocalcinosis; Oxalates

Primary hyperoxaluria (PH) is caused by genetic mutations resulting in oxalate overproduction leading to nephrolithiasis, nephrocalcinosis, extrarenal manifestations, chronic kidney disease, and end-stage renal disease. Advances in genetic testing techniques have improved our ability to efficiently and effectively obtain a definitive diagnosis of PH as well as easily screen at-risk family members. Similarly, advances in technologies related to intervening at the genetic and molecular level promise to change the way we treat patients with PH. In this review, we provide an update regarding the identification of underlying molecular and biochemical causes of inherited hyperoxalurias, clinical manifestations, and treatment strategies.

Topics: Alcohol Oxidoreductases; Fluid Therapy; Genetic Testing; Humans; Hyperoxaluria, Primary; Kidney Calculi; Kidney Transplantation; Lithotripsy; Liver Transplantation; Mutation; Nephrocalcinosis; Oxalates; Oxo-Acid-Lyases; Pyridoxine; Renal Replacement Therapy; Transaminases; Treatment Outcome

Although the primary hyperoxalurias (PH) are rare disorders, they are of considerable clinical importance in relation to calcium oxalate urolithiasis and as a cause of renal failure worldwide. Three distinct disorders have been described at the molecular level. The investigation of any child or adult presenting with urinary tract stones or nephrocalcinosis, must exclude PH as an underlying cause. This paper provides a practical approach to the investigation and diagnosis of PH, indicating the importance of distinguishing between the PH types for the purposes of targeting appropriate therapy. Conservative management is explored and the various transplant options are discussed.

Topics: Adult; Child; Diagnosis, Differential; Disease Management; Female; Humans; Hyperoxaluria, Primary; Male; Nephrocalcinosis; Nephrolithiasis; Oxalates; Renal Insufficiency; Urinary Calculi

Nephrocalcinosis may be defined as a generalized increase in the calcium content of the kidneys. This renal calcification may occur at a molecular, microscopic or macroscopic level leading to progressive amounts of renal damage. The major causes include those associated with an increase in urinary levels of calcium, oxalate and phosphate. Under these conditions, urine concentration and supersaturation leads to calcium crystal precipitation, which may be an intratubular event or initiate within the renal interstitium. The focus of discussion concerning renal calcification is often limited to factors that lead to renal stones (calculi and nephrolithiasis); however, nephrocalcinosis is a more sinister event, and often implies a serious metabolic defect. This review will discuss the hypotheses concerning initiating lesions of nephrocalcinosis using available laboratory and clinical studies and will examine whether new understanding of the molecular basis of tubulopathies, that lead to nephrocalcinosis, has given further insights.

Topics: Bartter Syndrome; Biological Transport; Calcium; Chemical Precipitation; Humans; Hyperoxaluria; Kidney; Kidney Diseases; Kidney Medulla; Kidney Tubules; Nephrocalcinosis; Oxalates; Phosphates

Topics: Calcium; Chemical Phenomena; Chemistry; Crystallization; Humans; Hyperparathyroidism; Intestinal Absorption; Intestinal Diseases; Kidney Tubules; Nephrocalcinosis; Osmolar Concentration; Oxalates

Management of most patients with calculous disease has been less than ideal in the past. Too often therapeutic efforts were limited to symptomatic calculi. Stones were allowed to pass or were removed, metabolic studies were incomplete, victims were dismissed and forgotten, and prophylactic measures were negligible and usually confined to milk restriction and use of distilled water. More patients were crippled with and died of recurrent calculous disease, urinary infection and progressive renal insufficiency than from any other upper urinary tract abnormality. During the last decade the development of a renal stone clinic at this institution has allowed a nephrourologic approach to the management of urolithiasis. This account of classification, diagnosis and management of the various syndromes associated with urolithiasis is based on the experiences gained during the last decade with this common but ill-understood urologic problem.

Topics: Acidosis, Renal Tubular; Adult; Child, Preschool; Cystinuria; Female; Humans; Hypercalcemia; Intestinal Diseases; Kidney Calculi; Male; Middle Aged; Nephrocalcinosis; Oxalates; Sepsis; Uric Acid; Xanthines

Topics: Bile; Bile Acids and Salts; Biological Transport; Biotransformation; Blind Loop Syndrome; Chemical Phenomena; Chemistry, Physical; Cholelithiasis; Cholestasis; Cholesterol; Diarrhea; Enterohepatic Circulation; Humans; Hyperlipidemias; Intestinal Diseases; Lipid Metabolism; Liver Diseases; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Pancreatitis; Stomach Ulcer

Topics: Hyperoxaluria; Metabolic Diseases; Nephrocalcinosis; Oxalates; Pathology; Urinary Calculi; Urine

Topics: Adolescent; Ascorbic Acid; Biochemical Phenomena; Biochemistry; Child; Classification; Diet; Genetics, Medical; Glycine; Glycolates; Humans; Hyperoxaluria, Primary; Infant; Kidney Calculi; Metabolic Diseases; Metabolism; Nephrocalcinosis; Oxalates; Pathology; Terminology as Topic; Uremia; Urine; Vitamin B 6 Deficiency

The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs).. Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian.. At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria.. These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.

Topics: Adult; Animals; Calcium; Dietary Fiber; Dietary Proteins; Female; Humans; Kidney Calculi; Male; Middle Aged; Nephrocalcinosis; Oxalates; Recurrence; Risk Factors; Time Factors; Urine

Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1.. For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox). We compared values among 3 groups: homozygous G170R, heterozygous G170R, and non-G170R AGXT variants both before and after initiating pyridoxine (B6).. Of 403 patients with PH1 in the registry, 83 met the inclusion criteria. Uox:cr decreased rapidly over the first 5 years of life. Both before and after B6 initiation, patients with non-G170R had the highest Uox:cr, 24-h Uox, and Pox. Patients with heterozygous G170R had similar Uox:cr to homozygous G170R prior to B6. Patients with homozygous G170R had the lowest 24-h Uox and Uox:cr after B6. Urinary oxalate excretion and Pox tend to decrease over time during childhood. eGFR over time was not different among groups.. Children with PH1 under 5 years old have relatively higher urinary oxalate excretion which may put them at greater risk for nephrocalcinosis and kidney failure than older PH1 patients. Those with homozygous G170R variants may have milder disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Adolescent; Child; Child, Preschool; Humans; Hyperoxaluria, Primary; Kidney Calculi; Nephrocalcinosis; Oxalates

Primary hyperoxaluria is a genetic disorder of the metabolism of glyoxylate, the precursor of oxalate. It is characterized by high endogenous production and excessive urinary excretion of oxalate, resulting in the development of calcium oxalate nephrolithiasis, nephrocalcinosis, and, in severe cases, end-stage kidney disease and systemic oxalosis. Three different forms of primary hyperoxaluria are currently known, each characterized by a specific enzymatic defect: type 1 (PH1), type 2 (PH2), and type 3 (PH3). According to currently available epidemiological data, PH1 is by far the most common form (about 80% of cases), and is caused by a deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase.. A survey on rare forms of nephrolithiasis and nephrocalcinosis with a focus on primary hyperoxaluria in the setting of Italian Nephrology and Dialysis Centers, using an online questionnaire, was recently conducted by the Project Group "Rare Forms of Nephrolithiasis and Nephrocalcinosis" of the Italian Society of Nephrology, with the aim of assessing the impact and management of this disorder in clinical practice in Italy.. Forty-five public and private Italian Centers participated in the survey, and responses to the questionnaire were provided by 54 medical professionals. The survey results indicate that 21 out of the 45 participating Centers are managing or have managed primary hyperoxaluria patients, most of whom are on dialysis, or are recipients of kidney transplants.. The data of this survey indicate the need to implement genetic testing in suspected cases of primary hyperoxaluria, not only in the setting of dialysis or transplantation, but also with the aim of encouraging early diagnosis of PH1, which is the only type of primary hyperoxaluria for which specific drug therapy is currently available.

Topics: Humans; Hyperoxaluria, Primary; Kidney Calculi; Nephrocalcinosis; Nephrologists; Nephrology; Oxalates

Lumasiran, a sub-cutaneous RNA-interference therapy, has been recently approved for primary hyperoxaluria type 1 (PH1), with doses and intervals according to body weight. Little is known as to its use in infants; the aim of this study was to describe treatment outcome in 3 infants who received lumasiran therapy before 2 years of age.. Patient 1 was diagnosed antenatally and received lumasiran from day 9. According to the product information template (PIT), he received monthly lumasiran (3 times at 6 mg/kg, then 3 mg/kg), with hyperhydration and potassium citrate. Despite decreased plasma oxalate levels, persistent normal kidney function, and good tolerance, kidney ultrasound performed after 2 months found nephrocalcinosis, without normalization of urinary oxalate (UOx). The dose was increased back to 6 mg/kg, inducing a normalization in UOx. Nephrocalcinosis started to improve at month 10. Patient 2 was diagnosed at 2.5 months (acute kidney failure); nephrocalcinosis was present from diagnosis. She received monthly lumasiran (6 mg/kg), with progressive decrease in UOx and substantial improvement in kidney function but stable nephrocalcinosis after 9 injections. Patient 3 was diagnosed fortuitously (nephrocalcinosis) at 3.5 months and received lumasiran before genetic diagnosis, leading to decreased UOx and maintenance of normal kidney function. Nephrocalcinosis improved after 5 injections.. This report presents the youngest children treated with lumasiran worldwide. Lumasiran seems effective without side effects in infants but does not completely prevent the onset of nephrocalcinosis in the most severe forms. Higher doses than those proposed in the PIT might be required because of hepatic immaturity.

Topics: Female; Humans; Hyperoxaluria, Primary; Infant; Male; Nephrocalcinosis; Oxalates; RNA, Small Interfering

In primary hyperoxaluria, increased hepatic oxalate production sometimes leads to severe nephrocalcinosis and early end-stage kidney disease. Oral administration of Oxalobacter formigenes (O. formigenes), an oxalate-degrading bacterium, is thought to derive oxalate from systemic sources by inducing net enteric oxalate secretion. Here, the impact of O. formigenes on nephrocalcinosis was investigated in an ethylene glycol rat model mimicking hepatic oxalate overproduction in primary hyperoxaluria. Eighteen rats were administered ethylene glycol (0.75% in drinking water) for 6 weeks, of which 9 were treated by oral gavage with O. formigenes and 9 received vehicle. Five control rats did not receive ethylene glycol or O. formigenes. Plasma and urinary oxalate levels, calcium oxalate crystalluria, urinary volume, fluid intake, and serum creatinine were monitored during the study. On killing, nephrocalcinosis was quantified. Ethylene glycol intake induced pronounced hyperoxalemia, hyperoxaluria, calcium oxalate crystalluria and nephrocalcinosis. Concomitant O. formigenes treatment partially prevented the ethylene glycol-induced increase in plasma oxalate and completely prevented nephrocalcinosis. Urinary oxalate excretion was not reduced by O. formigenes treatment. Nevertheless, absence of crystals in renal tissue of O. formigenes-treated ethylene glycol animals indicates that the propensity for oxalate to crystallize in the kidneys was reduced compared to non-treated animals. This is supported by the lower plasma oxalate concentrations in O. formigenes-treated animals. This study shows a beneficial effect of O. formigenes treatment on ethylene glycol-induced hyperoxalemia and nephrocalcinosis, and thus supports a possible beneficial effect of O. formigenes in primary hyperoxaluria.

Topics: Animals; Calcium Oxalate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Nephrocalcinosis; Oxalates; Oxalobacter formigenes; Rats

Primary hyperoxaluria type 1 is a rare autosomal recessive disorder leading to oxalate overproduction by deficiency in the liver-specific enzyme alanine-glyoxylate transaminase (AGT). Oxalate is a poorly soluble molecule that binds calcium and deposits in the entire organism leading to oxalosis. Its elimination is mainly carried out by kidneys. Hence the first manifestations are frequently of urinary concern and whitout any early care, progression of the disease to end-stage renal failure cannot be avoided. The only etiological treatment has long been combined liver-kidney transplantation because it restaures enzymatic function and replaces pathological kidneys. However, for a few years now, numerous studies are carried out on this subject and promising results have already been published with a new drug, lumasiran. From a clinical case, we describe the different options for the therapeutic management of primary hyperoxaluria type 1.. L’hyperoxalurie primitive de type 1 (HP1) est une maladie autosomale récessive rare entraînant une hyperproduction d’oxalate par déficit d’une enzyme hépatique : l’alanine-glyoxylate aminotransférase. L’oxalate est une petite molécule peu soluble qui se lie au calcium et forme des dépôts d’oxalate calcique dans l’ensemble de l’organisme : c’est l’oxalose. Son élimination est principalement rénale. Dès lors, les premières manifestations sont souvent d’ordre urinaire et, en l’absence de traitement précoce, la maladie évolue inévitablement vers l’insuffisance rénale terminale. Le seul traitement étiologique a longtemps été la transplantation combinée hépatique et rénale qui restaure une activité enzymatique et remplace les reins défaillants. Cependant, depuis quelques années, de nombreuses recherches sont réalisées à ce sujet et des résultats prometteurs ont déjà vu le jour avec le lumasiran. à partir d’un cas clinique, nous décrivons les différentes options de la prise en charge thérapeutique de l’HP1.

Topics: Humans; Hyperoxaluria, Primary; Nephrocalcinosis; Oxalates; RNA, Small Interfering

Nephrocalcinosis is associated with conditions that cause hypercalcemia and the increased urinary excretion of calcium, phosphate, and/or oxalate. A monogenic etiology is found in almost 30% of childhood-onset nephrocalcinosis which is also a common manifestation of primary hyperparathyroidism. We discuss a child with nephrocalcinosis and features mimicking primary hyperparathyroidism.. A 7-year-old girl presented with nephrocalcinosis. Hypercalciuria, hyperphosphaturia, mild hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels along with normal serum creatinine and absence of hypokalemic alkalosis suggested primary hyperparathyroidism. However, she was ultimately diagnosed with Bartter syndrome type 2 based on the presence of homozygous pathogenic variation in. This is the second reported case of late-onset Bartter syndrome type 2 without hypokalemic alkalosis. Patients with Bartter syndrome may present with high parathyroid hormone levels and hypercalcemia in addition to hypercalciuria. Thus, the present case suggests that the

Topics: Alkalosis; Bartter Syndrome; Calcium; Child; Creatinine; Female; Humans; Hypercalcemia; Hypercalciuria; Hyperparathyroidism, Primary; Nephrocalcinosis; Oxalates; Parathyroid Hormone; Phosphates

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

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

Primary Hyperoxaluria is a rare autosomal recessive hereditary disorder due to deficient alanine-glyoxylate aminotransferase enzyme with defective glyoxylate metabolism leading to excessive oxalate production and deposition into the tissues (oxalosis). Deposition of excessive calcium oxalates in nephrons leads to crystallization (nephrocalcinosis) which increases risk for end-stage renal disease. We are presenting a case of primary hyperoxaluria type I confirmed with genetic studies.

Topics: Humans; Hyperoxaluria, Primary; Image Processing, Computer-Assisted; Infant; Kidney; Kidney Transplantation; Liver Transplantation; Male; Mutation; Nephrocalcinosis; Oxalates; Prognosis; Renal Dialysis; Renal Insufficiency; Tomography, X-Ray Computed; Transaminases; Ultrasonography

Topics: Animals; Calcium; Calcium Oxalate; Calcium, Dietary; Nephrocalcinosis; Oxalates; Rats

Topics: Animals; Calcium Oxalate; Crystallization; Diet; Disease Models, Animal; Fibrosis; Glomerular Filtration Rate; Humans; Immunoglobulin G; Kidney; Male; Mice; Mice, Inbred C57BL; Nephrocalcinosis; Oxalates; Renal Insufficiency, Chronic; Transforming Growth Factor beta

Increased intestinal absorption of oxalate causes hyperoxaluria, a major risk factor for kidney stone disease. Intestinal colonization of recombinant probiotic bacteria expressing oxalate-degrading gene (OxdC) is an effective therapeutic option for recurrent calcium oxalate (CaOx) stone disease. Therefore, we aimed to develop food-grade probiotic L. plantarum secreting OxdC using lactococcal group II intron, Ll.LtrB and evaluate its oxalate degradation ability in vivo. Male Wistar albino rats were divided into four groups. The rats of group I received normal rat chow and drinking water. Groups II, III and IV rats received 5% potassium oxalate containing diet for 28 days. Groups III and IV rats received L. plantarum and food-grade recombinant L. plantarum respectively from 15 to 28 days. Biochemical parameters and crystalluria were analysed in 24 h urine samples. At the end of experimental period, rats were sacrificed; intestine and kidneys were dissected out for colonization studies and histopathological analysis. Herein, we found that the administration of recombinant probiotics significantly reduced the urinary oxalate, calcium, urea, and creatinine levels in rats of group IV compared to group II. Furthermore, colonization studies indicated that recombinant probiotics have gastrointestinal transit and intestinal colonization ability similar to that of wild-type bacteria. In addition, gene expression studies revealed down-regulation of OPN and KIM-1 among group IV rats. Histopathological analysis showed less evidence of nephrocalcinosis in group IV rats. In conclusion, the study demonstrates that food-grade L. plantarum secreting OxdC is capable of degrading intestinal oxalate and thereby prevent CaOx stone formation in experimental rats.

Topics: Alanine Racemase; Animals; Bacterial Proteins; Calcium; Calcium Oxalate; Carboxy-Lyases; Cell Adhesion Molecules; Creatinine; Disease Models, Animal; Gene Expression; Genes, Bacterial; Genomic Instability; Hyperoxaluria; Intestinal Mucosa; Intestines; Introns; Kidney; Kidney Calculi; Lactobacillus plantarum; Male; Mutagenesis; Nephrocalcinosis; Oxalates; Oxalic Acid; Probiotics; Rats; Rats, Wistar; Recombinant Proteins; RNA-Directed DNA Polymerase; Urea

Primary hyperoxaluria type 1 (PH1) is an inherited disease caused by mutations in alanine-glyoxylate aminotransferase (AGXT). It is characterized by abnormal metabolism of glyoxylic acid in the liver leading to endogenous oxalate overproduction and deposition of oxalate in multiple organs, mainly the kidney. Patients of PH1 often suffer from recurrent urinary tract stones, and finally renal failure. There is no effective treatment other than combined liver-kidney transplantation.. Microinjection was administered to PH1 rats. Urine samples were collected for urine analysis. Kidney tissues were for Western blotting, quantitative PCR, AGT assays and histological evaluation.. In this study, we generated a novel PH1 disease model through CRISPR/Cas9 mediated disruption of mitochondrial localized Agxt gene isoform in rats. Agxt-deficient rats excreted more oxalate in the urine than WT animals. Meanwhile, mutant rats exhibited crystalluria and showed a slight dilatation of renal tubules with mild fibrosis in the kidney. When supplied with 0.4% ethylene glycol (EG) in drinking water, mutant rats excreted greater abundance of oxalate and developed severe nephrocalcinosis in contrast to WT animals. Significantly elevated expression of inflammation- and fibrosisrelated genes was also detected in mutants.. These data suggest that Agxt-deficiency in mitochondria impairs glyoxylic acid metabolism and leads to PH1 in rats. This rat strain would not only be a useful model for the study of the pathogenesis and pathology of PH1 but also a valuable tool for the development and evaluation of innovative drugs and therapeutics.

Topics: Animals; CRISPR-Cas Systems; Disease Models, Animal; Glyoxylates; Hyperoxaluria, Primary; Mitochondria; Nephrocalcinosis; Oxalates; Rats; Rats, Transgenic; Transaminases

Topics: Alcohol Oxidoreductases; Animals; CRISPR-Cas Systems; Disease Models, Animal; Gene Editing; Genetic Therapy; HEK293 Cells; Humans; Hyperoxaluria, Primary; Male; Mice; Nephrocalcinosis; Oxalates

To investigate nephrocalcinosis due to hyperoxaluria induced by two different inducing agents in rats.. Forty Sprague-Dawley male rats were randomly distributed into four groups: Group 1 (Clinical control, n = 10); Group 2 (0.5% Ethylene Glycol + Vitamin D3, n = 10); Group 3 (1.25% Ethylene Glycol, n = 10); and Group 4 (5%Hydroxy L-proline, n = 10). Five animals from each group were euthanized after one week of follow-up (M1 Moment) and the remaining, after four weeks (M2 Moment). All animals underwent 24h urine dosages of calcium, oxalate, uric acid, citrate and serum creatinine. Histology and histomorphometric analyses were performed using Image J program in the hematoxylin-eosin stains. Calcium deposits in the renal parenchyma were quantified by PIXE technique (Proton Induced X-Ray Emission).. 24h urinary parameters did not show any significant variations after 28 days of experiment except by hyperoxaluria that was significantly higher in Group 3. Histomorphometric analyses showed a significantly higher nephrocalcinosis in Group 2 (p<0.01). The calcium deposits in the renal parenchyma were 10 and 100 times higher in Group 2 in comparison to other groups in the M1 and M2 moments, respectively.. The Group 2 (vitamin D3+Ethylene Glycol 0.5%) was the best model to induce nephrocalcinosis in rats after 28 days.

Topics: Animals; Calcium; Citric Acid; Hyperoxaluria; Kidney; Male; Nephrocalcinosis; Oxalates; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Time Factors; Uric Acid; Urine

Increased intestinal oxalate absorption leads to increased urinary oxalate excretion (secondary hyperoxaluria) and calcium oxalate crystal formation, contributing to nephrocalcinosis/lithiasis. Lanthanum carbonate is an intestinal phosphate binder that is orally administered to patients on dialysis to treat hyperphosphatemia. It is hypothesized that lanthanum can also bind oxalate, in addition to phosphate. We evaluated this in vitro and in vivo.. In vitro oxalate binding was evaluated by oxalate precipitation from a solution by lanthanum. In vivo oxalate absorption kinetics and the effect of lanthanum carbonate on nephrocalcinosis development were assessed in male Sprague-Dawley® rats that received 1) 1,000 mg lanthanum carbonate and oxalate, 2) carboxymethylcellulose and oxalate or 3) carboxymethylcellulose by gavage for up to 12 hours (kinetics) or 7 days (nephrocalcinosis). Plasma and urinary oxalate concentrations were measured at several time points after gavage. The degree of nephrocalcinosis was assessed histomorphometrically on von Kossa stained sections and by measuring total calcium content in renal tissue.. In vitro lanthanum bound oxalate in a pH range comparable to the range of the intestine. In vivo oxalate administration in untreated animals resulted in a biphasic pattern of increased plasma oxalate levels, which was almost abolished in lanthanum treated rats. In the urine of treated rats oxaluria and calcium oxalate crystalluria were blunted. Moreover, significantly decreased nephrocalcinosis was observed compared with that in untreated rats.. Lanthanum carbonate is a promising agent for the future prevention/treatment of secondary hyperoxaluria.

Topics: Animals; Intestinal Absorption; Lanthanum; Male; Nephrocalcinosis; Oxalates; Rats; Rats, Sprague-Dawley

Primary hyperoxaluria type 1 (PH1) and type 2 (PH2) are rare genetic diseases that result from deficiencies in glyoxylate metabolism. The increased oxalate synthesis that occurs can lead to kidney stone formation, deposition of calcium oxalate in the kidney and other tissues, and renal failure. Hydroxyproline (Hyp) catabolism, which occurs mainly in the liver and kidney, is a prominent source of glyoxylate and could account for a significant portion of the oxalate produced in PH. To determine the sensitivity of mouse models of PH1 and PH2 to Hyp-derived oxalate, animals were fed diets containing 1% Hyp. Urinary excretions of glycolate and oxalate were used to monitor Hyp catabolism and the kidneys were examined to assess pathological changes. Both strains of knockout (KO) mice excreted more oxalate than wild-type (WT) animals with Hyp feeding. After 4 wk of Hyp feeding, all mice deficient in glyoxylate reductase/hydroxypyruvate reductase (GRHPR KO) developed severe nephrocalcinosis in contrast to animals deficient in alanine-glyoxylate aminotransferase (AGXT KO) where nephrocalcinosis was milder and with a lower frequency. Plasma cystatin C measurements over 4-wk Hyp feeding indicated no significant loss of renal function in WT and AGXT KO animals, and significant and severe loss of renal function in GRHPR KO animals after 2 and 4 wk, respectively. These data suggest that GRHPR activity may be vital in the kidney for limiting the conversion of Hyp-derived glyoxylate to oxalate. As Hyp catabolism may make a major contribution to the oxalate produced in PH patients, Hyp feeding in these mouse models should be useful in understanding the mechanisms associated with calcium oxalate deposition in the kidney.

Topics: Alcohol Oxidoreductases; Animal Feed; Animals; Diet; Hydroxyproline; Hyperoxaluria; Male; Mice; Mice, Knockout; Nephrocalcinosis; Oxalates; Transaminases

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

Primary hyperoxaluria type I (PH1) is an inborn error of metabolism caused by deficiency of the hepatic enzyme alanine-glyoxylate aminotransferase (AGXT or AGT) which leads to overproduction of oxalate by the liver and subsequent urolithiasis and renal failure. The current therapy largely depends on liver transplantation, which is associated with significant morbidity and mortality. To explore an alternative treatment, we used somatic gene transfer in a mouse genetic model for PH1 (Agxt1KO). Recombinant adeno-associated virus (AAV) vectors containing the human AGXT complementary DNA (cDNA) were pseudotyped with capsids from either serotype 8 or 5, and delivered to the livers of Agxt1KO mice via the tail vein. Both AAV8-AGXT and AAV5-AGXT vectors were able to reduce oxaluria to normal levels. In addition, treated mice showed blunted increase of oxaluria after challenge with ethylene glycol (EG), a glyoxylate precursor. In mice, AGT enzyme activity in whole liver extracts were restored to normal without hepatic toxicity nor immunogenicity for the 50 day follow-up. In summary, this study demonstrates the correction of primary hyperoxaluria in mice treated with either AAV5 or AAV8 vectors.

Topics: Animals; Blotting, Western; Capsid Proteins; Dependovirus; Disease Models, Animal; Ethylene Glycol; Gene Transfer Techniques; Genetic Therapy; Humans; Hyperoxaluria, Primary; Liver; Mice; Mice, Knockout; Nephrocalcinosis; Oxalates; Phenotype; Transaminases; Urolithiasis

The spectrum of primary hyperoxaluria type I is extremely heterogeneous, ranging from singular to recurrent urolithiasis and early end-stage renal disease (ESRD). In infantile oxalosis, the most devastating form, ESRD occurs as early as within the first weeks of life. No kidney replacement therapy sufficiently removes endogenously overproduced oxalate. However, curative combined liver-kidney transplant often is impracticable in small infants. Oxalobacter formigenes (O formigenes), an anaerobic oxalate-degrading bacterium, is a colonizer of the healthy human colon. Oral administration of O formigenes has been shown to significantly decrease urine and plasma oxalate levels in patients with primary hyperoxaluria. We report compassionate use of O formigenes in two 11-month-old girls with infantile oxalosis and ESRD. They received O formigenes twice a day for 4 weeks (or until transplant). Dialysis regimens were unchanged. Plasma oxalate levels decreased from >110 μmol/L before to 71.53 μmol/L under treatment in patient 1 and from >90 to 68.56 μmol/L (first treatment period) and 50.05 μmol/L (second treatment period) in patient 2. O formigenes was well tolerated. No serious side effects were reported. Extremely increased plasma oxalate levels in patients with infantile oxalosis may enable intestinal elimination of endogenous oxalate in the presence of O formigenes. Therefore, O formigenes therapy may be helpful as a bridging procedure until transplant in such patients.

Topics: Administration, Oral; Feces; Female; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Infant; Kidney Transplantation; Mutation, Missense; Nephrocalcinosis; Oxalates; Oxalobacter formigenes; Renal Insufficiency; Transaminases

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

Urolithiasis, a condition in which stones are present in the urinary system, including the kidneys and bladder, is a poorly understood yet common disorder worldwide that leads to significant health care costs, morbidity, and work loss. Acetaminophen-induced liver damage is a major cause of death in patients with acute liver failure. Kidney and urinary stones and liver toxicity are disturbances linked to alterations in oxalate and sulfate homeostasis, respectively. The sulfate anion transporter-1 (Sat1; also known as Slc26a1) mediates epithelial transport of oxalate and sulfate, and its localization in the kidney, liver, and intestine suggests that it may play a role in oxalate and sulfate homeostasis. To determine the physiological roles of Sat1, we created Sat1-/- mice by gene disruption. These mice exhibited hyperoxaluria with hyperoxalemia, nephrocalcinosis, and calcium oxalate stones in their renal tubules and bladder. Sat1-/- mice also displayed hypersulfaturia, hyposulfatemia, and enhanced acetaminophen-induced liver toxicity. These data suggest that Sat1 regulates both oxalate and sulfate homeostasis and may be critical to the development of calcium oxalate urolithiasis and hepatotoxicity.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anion Transport Proteins; Antiporters; Homeostasis; Hyperoxaluria; Intestinal Mucosa; Intestines; Ion Transport; Kidney Tubules; Liver; Liver Failure, Acute; Mice; Mice, Knockout; Nephrocalcinosis; Oxalates; Sulfate Transporters; Sulfates; Urinary Bladder; Urolithiasis

Hyperoxaluria is a major risk factor for recurrent urolithiasis and nephrocalcinosis. We tested an oral therapy with a crystalline, cross-linked formulation of oxalate-decarboxylase (OxDc-CLEC) on the reduction of urinary oxalate and decrease in the severity of kidney injury in two models: AGT1 knockout mice (AGT1KO) in which hyperoxaluria is the result of an Agxt gene deficiency, and in AGT1KO mice challenged with ethylene glycol (EG).. Four different doses of OxDc-CLEC mixed with the food, or placebo were given to AGT1KO mice (200 mg/day, n = 7) for 16 days and to EG-AGT1KO mice (5, 25, and 80 mg, n = 11) for 32 days.. Oral therapy with 200 mg OxDc-CLEC reduced both urinary (44%) and fecal oxalate (72%) in AGT1KO mice when compared to controls. Similarly, in EG-AGT1KO mice, each of the three doses of OxDc-CLEC produced a 30-50% reduction in hyperoxaluria. A sustained urinary oxalate reduction of 40% or more in the 80 mg group led to 100% animal survival and complete prevention of nephrocalcinosis and urolithiasis.. These data suggest that oral therapy with OxDc-CLEC may reduce hyperoxaluria, prevent calcium oxalate nephrocalcinosis and urolithiasis, and can represent a realistic option for the treatment of human hyperoxaluria, independent of cause.

Topics: Administration, Oral; Amino Acid Transport Systems; Animals; Carboxy-Lyases; Chemistry, Pharmaceutical; Crystallization; Disease Models, Animal; Ethylene Glycol; Feces; Hyperoxaluria; Kidney; Male; Mice; Mice, Knockout; Nephrocalcinosis; Oxalates; Peptide Hydrolases; Urolithiasis

We report a case of a woman with secondary oxalosis after jejunoileal bypass surgery for obesity, who presented with oxalate stone disease and renal insufficiency requiring dialysis. Thirty years after surgery, longstanding osteoarticular symptoms were recognized as oxalate arthritis. Eventually, she also developed oxalate vasculitis, which improved with corticoid treatment and intensification of dialysis. Work-up for kidney transplantation revealed AA amyloidosis on gastric and colonic biopsies. Since no other cause of chronic inflammation could be identified, it was concluded that the amyloidosis was secondary to oxalate arthritis and vasculitis. To our knowledge, this is the first report on this association.

Topics: Amyloidosis; Arthritis; Female; Humans; Hyperoxaluria; Jejunoileal Bypass; Malabsorption Syndromes; Middle Aged; Nephrocalcinosis; Obesity, Morbid; Oxalates; Time Factors; Vasculitis

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

Topics: Adult; Calcium; Disease Progression; Genetic Predisposition to Disease; Global Health; Humans; Hyperoxaluria; Incidence; Nephrocalcinosis; Oxalates; Prognosis; Risk Factors

Nephrocalcinosis is the result of a myriad of hereditary or acquired diseases in the calcium, phosphate or oxalate metabolism that lead to deposition of calcium containing precipitates within the kidney. Nephrocalcinosis and nephrolithiasis are pathophysiologically tightly related and often co-exist. In the case of recurrent nephrolithiasis, nephrocalcinosis has to be excluded. Stone analysis can yield important clues to the underlying disease process. The best way to diagnose nephrocalcinosis and an accompanying nephrolithiasis is by native computer tomography scans. Untreated, nephrocalcinosis will lead to a progressive decline in renal function and eventually to end stage renal disease. Thus, for each case, the underlying disease process has to be determined and a causative therapy initiated.

Topics: Calcium; Diagnosis, Differential; Humans; Hyperparathyroidism, Primary; Kidney; Kidney Calculi; Kidney Function Tests; Nephrocalcinosis; Oxalates; Parathyroid Hormone; Phosphates; Tomography, X-Ray Computed

It is hypothesized that oxalate plays an active role in calcium oxalate (CaOx) nephrocalcinosis and oxalate driven nephrolithiasis by interacting with the kidney. We developed an adjustable, nonprecursor, continuous infusion model of hyperoxaluria and CaOx nephrocalcinosis to investigate this hypothesis. Minipumps containing PBS or KOx (60-360 micromol/day; n = 5-7/dose) were implanted subcutaneously in male Sprague-Dawley rats on D0 and D6. Rats were killed on D13. Oxalate excretion and CaOx crystalluria were monitored by 20+4 h urine collections. Localization and content of intrarenal crystals were determined on frozen sections using polarization and microFTIR. Oxalate excretion was significantly elevated in all KOx rats (P < or = 0.005). CaOx crystalluria was most persistent in the 240-360 micromol/day KOx rats, but even 60 micromol/day KOx rats showed sporadic crystalluria. One hundred percent of KOx rats had CaOx nephrocalcinosis as confirmed by microFTIR. Most crystals were localized to the lumens of the corticomedullary collecting ducts. A few crystals are localized just under the papillar urothelium. The minipump model is the first model of hyperoxaluria to provide continuous infusion of oxalate. It permits control of the levels of hyperoxaluria, crystalluria and CaOx nephrocalcinosis. The level of sustained hyperoxaluria and CaOx nephrocalcinosis induced by treatment with 360 micromol/day KOx for 13D models the conditions frequently observed in jejunoileal bypass patients. Adjustments in the length of treatment and level of hyperoxaluria may allow this model to also be used to study the oxalate driven CaOx-nephrolithiasis common in patients with hyperoxaluria due to other causes.

Topics: Animals; C-Reactive Protein; Calcium Oxalate; Crystallization; Infusion Pumps, Implantable; Kidney; Male; Nephrocalcinosis; Oxalates; Rats; Rats, Sprague-Dawley

Hyperoxaluria has been incriminated to account for the increased incidence of urolithiasis or nephrocalcinosis in patients with cystic fibrosis (CF). Hyperoxaluria presumably is caused by fat malabsorption and the absence of such intestinal oxalate-degrading bacteria as Oxalobacter formigenes. To better elucidate its pathophysiological characteristics, we prospectively studied patients with CF by determining these parameters and performing renal ultrasonography twice yearly.. In addition to routine tests in urine (lithogenic and stone-inhibitory substances), the presence of O formigenes was tested in stool, plasma oxalate was measured, and a [13C2]oxalate absorption test was performed in 37 patients with CF aged 5 to 37 years (15 females, 22 males) who were constantly hyperoxaluric before the study.. Hyperoxaluria (oxalate, 46 to 141 mg/1.73 m2/24 h [0.51 to 1.57 mmol/1.73 m2/24 h]; normal, < 45 mg/1.73 m2/24 h [< 0.5 mmol/1.73 m2/24 h]) was now found in 24 patients (64.8%). Plasma oxalate levels were elevated in 6 patients (7.92 to 19.5 micromol/L; normal, 6.3 +/- 1.1 micromol/L). Oxalobacter species were detected in only 1 patient. Intestinal oxalate absorption was elevated (11.4% to 28.5%; normal, < 10%) in 23 patients. Hypocitraturia was present in 17 patients (citrate, 0.35 to 2.8 g/1.73 m2/24 h [0.2 to 1.1 mmol/1.73 m2/24 h]; normal female, > 2.8 mg/1.73 m2/24 h [> 1.6 mmol/1.73 m2/24 h]; male, > 3.3 mg/1.73 m2/24 h [> 1.9 mmol/1.73 m2/24 h]). Urine calcium oxalate saturation was elevated in 17 patients (5.62 to 28.9 relative units; normal female, < 5.5 relative units; male, < 6.3 relative units). In 16% of patients, urolithiasis (n = 2) or nephrocalcinosis (n = 4) was diagnosed ultrasonographically.. Absorptive hyperoxaluria and hypocitraturia are the main culprits for the increased incidence of urolithiasis and nephrocalcinosis in patients with CF. We advocate high fluid intake, low-oxalate/high-calcium diet, and alkali citrate medication, if necessary. Additional studies are necessary to determine the influence of Oxalobacter species or other oxalate-degrading bacteria on oxalate handling in patients with CF.

Topics: Adolescent; Adult; Calcium, Dietary; Carbon Isotopes; Child; Child, Preschool; Citrates; Cystic Fibrosis; Dietary Fats; Feces; Female; Fluid Therapy; Humans; Hyperoxaluria; Intestinal Absorption; Intestines; Malabsorption Syndromes; Male; Nephrocalcinosis; Oxalates; Oxalobacter formigenes; Risk; Urinary Calculi

We report a case of severe nephrocalcinosis related to hypercalcaemia in a newborn with glucose-galactose malabsorption. He presented with poor growth and was noted to have polyuria, which was later recognised to be severe watery diarrhoea. We discuss the possible aetiological factors for nephrocalcinosis in this condition.

Topics: Calcium; Diarrhea; Galactose; Glucose; Growth Disorders; Humans; Hypercalcemia; Infant, Newborn; Karyotyping; Kidney; Malabsorption Syndromes; Male; Nephrocalcinosis; Oxalates; Polyuria; Ultrasonography

Very low birth weight (VLBW) infants are at risk to develop nephrocalcinosis (NC). NC may result from spontaneous or therapy-induced imbalance between promoters and inhibitors of crystallization in the urine. However, data on "normal" urinary excretions of these parameters in VLBW infants are sparse. Therefore, we prospectively examined the urinary excretion of calcium, oxalate, uric acid, and citrate in VLBW infants during the first 8 weeks of life.. Urine samples were collected once weekly in 124 VLBW infants. NC appeared in 16 infants, whose data were separately analyzed. The remaining 108 infants were divided into subgroups: A, <1000 g (N = 53); and B, 1000 to 1500 g (N = 55). Random urine samples were analyzed and the results were expressed as molar creatinine ratios. Calcium/citrate and oxalate/citrate expressed the risk for calcium oxalate crystallization.. In group A, citrate excretion was lower at weeks 2 to 5 and 7; calcium/citrate was higher in weeks 2, 4, and 7; oxalate/citrate was higher in weeks 3, 4, 7, and 8; and calcium/creatinine ratio was higher in week 4 (P < 0.05). Citrate/creatinine ratios were low in nine infants with NC. Oxalate/creatinine and calcium/creatinine were elevated in five and calcium/citrate was increased in nine infants with NC.. Hypocitraturia is a major risk factor for NC in VLBW infants, especially in those <1000 g. The urinary excretions in VLBW infants seem to depend on birth weight, age, and clinical condition. Hence, supplementation with alkali citrate may have a beneficial effect in the prevention of NC.

Topics: Calcium; Citric Acid; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Very Low Birth Weight; Male; Nephrocalcinosis; Oxalates; Prospective Studies; Risk Factors; Uric Acid

A crucial role for cell-crystal interactions in the development of urolithiasis (UL) and nephrocalcinosis (NC) was previously observed in experiments with different cell lines mimicking renal epithelial cells. It was found that such cell-crystal interactions lead to tubular damage and/or or dysfunction. To find further proof for these observations, we measured the urinary N-acetyl-beta- d-glucosaminidase (NAG) excretion, a marker of proximal tubular damage, in children with UL or NC and in children with an increased risk of UL. We enrolled 142 children aged 4-16 years (mean 9.67+/-3.40 years), with 50 children having UL, 30 children with a history of UL (ULH), 20 patients with NC, 34 children with secondary hyperoxaluria (HyOx), and 8 children with idiopathic hypercalciuria (HC). Normal urinary NAG/Cr values were determined in a group of 70 healthy children aged 4-16 years (mean 10.06+/-3.97 years). The urinary NAG activity was measured using a colorimetric method and the results were expressed as molar creatinine (Cr) ratios. The highest median NAG/Cr ratios were found in children with UL plus hematuria (0.72 U/mM) and in children with UL (0.67 U/mM) or NC (0.48 U/mM), which were all significantly higher than those in controls (0.28 U/mmol, P<0.001 and P<0.05). The NAG/Cr ratios were increased above the upper normal reference interval of 0.63 U/mM (95th percentile) in 28 of 50 (56%) children with UL and in 9 of 20 (45%) children with NC. Although the ULH group also had significantly higher median NAG/Cr ratios (0.36 U/mM) compared with controls, the NAG/Cr ratio was only elevated in 4 of 30 (13%) patients. NAG values in children with secondary HyOx or HC were not different from controls. No correlation was found between the NAG/Cr ratios and the urinary excretion of oxalate or calcium. In conclusion, UL or NC may result in proximal tubular injury, which is rather the consequence of disease activity and of the mechanical influence of calculi, than of the metabolic background. The mechanism of cell damage in these conditions however, seems to be complex. Neither HyOx nor HC alone were sufficient to induce severe tubular damage expressed as an increase in NAG excretion in our patients.

Topics: Acetylglucosaminidase; Adolescent; Biomarkers; Calcium; Child; Child, Preschool; Female; Humans; Male; Nephrocalcinosis; Oxalates; Risk Factors; Urinary Calculi

An anomalous n-6 polyunsaturated fatty acid composition in plasma and erythrocyte membrane phospholipids, namely increased levels of arachidonic acid (AA), has been reported in calcium nephrolithiasis and has been proposed to play an important role in its pathogenesis. To confirm this, in rats we modified phospholipid AA levels by dietary manipulation of the delta-6-desaturase, the rate-limiting enzyme of the fatty acid biosynthetic pathway, and evaluated the effect on cellular and renal functions predisposing to lithogenesis. Increased AA levels led to conditions at risk for nephrolithiasis: higher oxalate flux and lower sodium cotransport in erythrocytes and a rise in urinary prostaglandin E2, calcium, sodium, and oxalate levels; reduced AA levels reversed these changes. In vitro, in human erythrocytes the incorporation of exogenous AA into membranes increased band 3 protein phosphorylation directly activating the Ser/Thr protein kinase CK1 and induced a parallel raise in band 3-mediated oxalate transport. These findings demonstrate the pivotal role of phospholipid AA in modulating erythrocyte and renal transport of calcium and oxalate.

Topics: Animals; Anion Exchange Protein 1, Erythrocyte; Arachidonic Acid; Calcium; Casein Kinase II; Casein Kinases; Diet; Dinoprostone; Erythrocyte Membrane; Erythrocytes; Fatty Acid Desaturases; Humans; Linoleoyl-CoA Desaturase; Liver; Male; Nephrocalcinosis; Oxalates; Phospholipids; Protein Kinases; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Sodium

Topics: Female; Fetal Death; Furosemide; Humans; Infant, Newborn; Kidney Tubules; Nephrocalcinosis; Oxalates; Pregnancy

Objective. The purpose of this study was to induce nephrocalcinosis (NC) in rabbits with phosphate, vitamin D, oxalate and furosemide, to determine the effect on renal function and to correlate detection on ultrasound (US) and computed tomography (CT) with pathology. Materials and methods. Seventy-five immature New Zealand white rabbits were divided into five groups of 15. In each group, 5 animals were controls and 10 were given oral phosphate, furosemide, vitamin D or oxalate. Unilateral nephrectomy was performed at 3-6 weeks, and 5 rabbits of each test group were withdrawn from the substance. Weekly US was performed as well as US, CT and measurement of serum creatinine at the time of nephrectomy and prior to planned demise. Results. A total of 140 kidneys in 75 rabbits had both pathological and US correlation, with CT correlation in 126. Forty rabbits developed nephrocalcinosis with early (post nephrectomy at 3-6 weeks) or late (post demise at 12-20 weeks) pathological correlation obtained in 53 kidneys. Forty-one of these kidneys were from test animals: 23 developed NC early, 18 late. Twelve controls developed NC: 4 early, 8 late. Comparing US and CT to pathology, the sensitivity was 96% for US, 64% for CT. Specificity was 85% for US and 96% for CT. In 109 kidneys, information on serum creatinine level was available to correlate with pathology. The mean creatinine level was 138 mmol/l for those with NC and 118 mmol/l for those without NC (P<0.001). Conclusion. In this study, the presence of NC was significantly associated with increasing serum creatinine. Overall, US was more sensitive and CT was more specific in the detection of NC.

Topics: Animals; Creatinine; Furosemide; Kidney; Nephrocalcinosis; Oxalates; Phosphates; Rabbits; Tomography, X-Ray Computed; Ultrasonography; Vitamin D

Topics: Acute Kidney Injury; Adult; Bone Diseases; Humans; Joint Diseases; Kidney; Male; Nephrocalcinosis; Oxalates; Renal Dialysis; Time Factors

To study the effect of diuretic drugs on urinary oxalate excretion in premature infants, and to examine the relationship between urinary calcium and sodium excretion in premature infants.. We measured urinary oxalate, calcium, and sodium excretion in 32 premature infants at approximately 34 weeks gestational age. Seven infants were receiving furosemide, 5 infants were receiving thiazide, 8 infants were receiving furosemide plus thiazide, and 12 infants who were not receiving diuretics served as controls.. Urinary oxalate to creatinine ratios in infants receiving furosemide (0.48 +/- .26), thiazide (0.54 +/- .20), furosemide plus thiazide (0.44 +/- .19), and control infants (0.51 +/- .43) were similar by analysis of variance (ANOVA). Data expressed as oxalate concentration gave similar results. Urinary calcium to creatinine ratios in infants receiving furosemide (0.81 +/- .30), thiazide (0.54 +/- .25), furosemide plus thiazide (0.75 +/- .49), and control infants (0.37 +/- .25) were similar by ANOVA. The urinary calcium concentration in infants receiving furosemide plus thiazide (0.085 +/- 0.042 mg/mL) was different from control infants (0.044 +/- .023) by ANOVA and Student-Newman-Keuls test. Urinary calcium to creatinine ratio was correlated with sodium to creatinine ratio (r = .751).. Urinary oxalate excretion in premature infants is not affected by diuretic drugs. Urinary sodium and calcium excretion are closely linked in sodium supplemented premature infants receiving diuretics. The calciuric effect of furosemide is not decreased by the addition of thiazide in premature infants receiving sodium supplements.

Topics: Analysis of Variance; Calcium; Diuretics; Furosemide; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Nephrocalcinosis; Oxalates; Sodium

Although nephrocalcinosis is a classical finding in primary hyperoxaluria type 1 (PH 1) associated with a poor renal survival it is exceptional in patients with PH type 2 (PH 2), characterized by a more favorable outcome. We describe an 8-month-old girl who suffered from recurrent urinary tract infections. Imaging studies revealed a profound corticomedullary nephrocalcinosis with no evidence of calculi. Urinary oxalate and D-glycerate excretion were massively elevated, while urinary glycolate or glyoxylate could not be detected, confirming the diagnosis of PH 2. Although the nephrocalcinosis progressed radiologically, renal function remained stable for over 2 years. Only further follow-up will show whether the associated nephrocalcinosis worsens the prognosis of our patient and of PH 2 in general.

Topics: Child; Female; Glyceric Acids; Glycolates; Glyoxylates; Humans; Hydrogen-Ion Concentration; Hyperoxaluria, Primary; Kidney; Nephrocalcinosis; Oxalates; Radiography; Ultrasonography; Urinary Calculi

Nephrocalcinosis was described in preterm infants by several authors who tried to determine its association with hypercalciuria and furosemide therapy. We evaluated these potential mechanisms along with other lithogenic factors not previously studied in 10 premature babies. Hypercalciuria was an inconsistent finding like in other reports; elevated uric acid excretion and hyperoxaluria were observed in 5 and 6 cases, respectively. The aminocid excretion was normal in all infants. Our data suggest that in addition to hypercalciuria, other lithogenic factors may play a role in the pathophysiology of nephrocalcinosis of premature infants.

Topics: Glycosuria; Humans; Hypercalcemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Nephrocalcinosis; Oxalates; Proteinuria; Renal Aminoacidurias; Uric Acid

Evidence for the suitability of spot urines for selective screening in children was obtained by comparing the 24-hour urinary oxalate excretion with the ratio of urinary oxalate to creatinine [mmol/mol] in spontaneously voided urine samples. Spot urines of 169 healthy children aged 1 day to 13 years were analysed in order to establish reference values for the urinary oxalate/creatinine ratio in relation to age and body surface area. Oxalate was measured by automated ion chromatography. Results showed an inverse relationship between the oxalate/creatinine ratio and age. The highest ratios, 131 +/- 57 mmol/mol (mean +/- 2 SD), were found in infants. At age two years, the ratio was 84 +/- 55, at age five years 56 +/- 35, and for children older than ten years 42 +/- 31. This finding can be explained by the gain of muscle mass and hence increased creatinine production with increasing age. Data for the urinary oxalate/creatinine ratio are presented according to body surface area for the assessment of children with abnormal growth. In 19 urine samples from nine patients with primary hyperoxaluria, the oxalate/creatinine ratio greatly exceeded (286-2022 mmol/mol) the above reference ranges. We therefore propose the determination of the oxalate/creatinine ratio in spot urines for the selective screening for hyperoxaluria in children with nephrocalcinosis or urolithiasis.

Topics: Adolescent; Aging; Body Surface Area; Child; Child, Preschool; Creatinine; Female; Humans; Hyperoxaluria; Infant; Infant, Newborn; Male; Nephrocalcinosis; Oxalates; Reference Values; Urinary Calculi

Hypercalciuria and nephrocalcinosis are not uncommon in patients with Wilson's disease but have only once been reported as the presenting sign. We diagnosed Wilson's disease in a 17-year-old male patient 6 years after his first episode of gross hematuria and 2 years after detection of hypercalciuria and nephrocalcinosis. Therapy with penicillamine resulted only in a moderate reduction of urinary calcium excretion but oxalate excretion increased.

Topics: Adolescent; Calcium; Hematuria; Hepatolenticular Degeneration; Humans; Kidney Calculi; Male; Nephrocalcinosis; Oxalates; Oxalic Acid; Penicillamine; Time Factors; Ultrasonography

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

The synergistic interaction of fructose and magnesium (Mg) deficiency on kidney calcification was compared in male and female rats. Male and female weanling rats were divided into four dietary groups: fructose or starch, with or without Mg. Rats were fed their respective diets for 9 weeks, and 24 h urine was collected to measure urinary output, pH, Mg, calcium (Ca), and oxalic acid. Rats were fasted overnight. After decapitation, blood was collected immediately, and kidneys were removed to determine their Mg and Ca content. Dietary fructose significantly increased kidney Ca in female rats fed deficient or adequate Mg diet and in male rats fed Mg-deficient diet only; the greatest kidney calcification occurred in female rats fed Mg-deficient diet (P less than 0.0001). Even in starch groups female rats fed the Mg-deficient diet showed some kidney Ca accumulation. The synergistic interaction of fructose and magnesium deficiency on nephrocalcinosis was significantly greater in female than in male rats. Low urinary output, optimal pH 6.8 for calcium phosphate precipitation, hypercalcaemia, hypercalciuria, hypomagnesuria, and low ratio of urinary Mg to Ca may independently or multifactorially contribute to nephrocalcinosis. The possible mechanism of this interaction is discussed.

Topics: Analysis of Variance; Animals; Calcium; Dietary Carbohydrates; Female; Fructose; Hydrogen-Ion Concentration; Kidney; Magnesium; Magnesium Deficiency; Male; Nephrocalcinosis; Oxalates; Oxalic Acid; Rats; Rats, Inbred Strains; Sex Factors; Starch

The low incidence of atherosclerosis and other degenerative diseases including stone disease in the Greenland Eskimo has been attributed to their high consumption of oily fish with its high concentration of eicosapentaenoic acid (EPA). Man cannot synthesis EPA from the precursor essential fatty acid, linolenic acid, and can only assimilate preformed EPA present in fish and fish oil, to bring about a change in the pathway of eicosanoid metabolism from the n-6 to the n-3 series. With a westernised diet the oxygenated products of renal prostaglandin synthesis are metabolites of the n-6 series and these are known to play an important role in several pathophysiological states including stone disease. Our previous studies have shown a relationship between prostaglandin activity and urinary calcium excretion and it would seem that the initiating factor/s for stone formation trigger the mechanisms for prostaglandin synthesis resulting in the biochemical abnormalities associated with stone disease. The Eskimo may be protected from these events by possession of an eicosanoid metabolism that follows an n-3 pathway. To test this hypothesis experiments were performed using an animal model of nephrocalcinosis. The animals were divided into three groups; one group was given an intra-peritoneal injection of 10% calcium gluconate daily for 10 days to induce nephrocalcinosis; a second group was fed MaxEPA fish oil before and during the calcium gluconate injections and a third group only received an intra-peritoneal injection of N saline. A group of 12 recurrent, hypercalciuric/hyperoxaluric stone-formers were treated with fish oil for eight weeks to study the effects on solute excretion. Nephrocalcinosis, which was readily produced in the control animals, was prevented in the experimental animals by pre-treatment with fish oil and urine calcium excretion was significantly reduced. The urinary calcium and oxalate excretion in the recurrent, hypercalciuric stone-formers was significantly reduced with fish oil treatment over an eight week period. There were no untoward side-effects. These studies indicate that the incorporation of EPA in the diet as a substitute metabolic pathway could be a unique way of correcting the biochemical abnormalities of idiopathic urolithiasis.

Topics: Adult; Aged; Animals; Calcium; Disease Models, Animal; Drug Evaluation; Drug Evaluation, Preclinical; Eicosapentaenoic Acid; Female; Humans; Kidney; Kidney Calculi; Male; Microradiography; Middle Aged; Nephrocalcinosis; Oxalates; Oxalic Acid; Rats; Rats, Inbred Strains; Recurrence; Spectrophotometry, Atomic

Administration of high doses of vitamin D3 (2,600 IU/100 ml of drinking water) to adult rats, for one month, significantly altered renal function (P less than 0.01) and enhanced renal accumulation of oxalate (71.44 x 18.82 micrograms/g of tissue in treated rats vs 38.87 +/- 11.96 micrograms/g in untreated rats; P less than 0.001), phosphate (1.388 +/- 188 micrograms/g in treated rats vs 870 +/- 171 micrograms/g in untreated rats; P less than 0.01) and calcium (477 +/- 107 micrograms/g in treated rats vs 326 +/- 104 micrograms/g in untreated rats; P less than 0.01). Urinary analyses of principal promotors and inhibitors of lithogenesis revealed high calcium excretion (1,576 +/- 0.419 mg/24 hr in treated rats vs 0.969 +/- 0.214 mg/24 hr in untreated rats; p less than 0.01) and decreased magnesium excretion (0.330 +/- 0.135 mg/24 hr in treated rats vs 0.910 +/- 0.168 mg/24 hr in untreated rats; p less than 0.001). Microscopic calcium deposits were found in the medulla, especially in renal papilla. These results suggested that vitamin D3, when administered at high doses for a long time, may induce nephrocalcinosis and alter renal function.

Topics: Animals; Calcium; Cholecalciferol; Creatinine; Kidney; Kidney Calculi; Male; Nephrocalcinosis; Oxalates; Oxalic Acid; Phosphates; Rats; Rats, Inbred Strains; Uric Acid

We report a case of primary oxalosis in a 12-year old girl. This unusual observation exemplifies two diagnostic pitfalls, i.e. false urinary tract infections and technical difficulties in accurately measuring oxalate urinary excretion. On the basis of this case and a review of the literature, we discuss diagnostic and therapeutic methods. Early diagnosis of the disease is important in order to monitor the patient and provide genetic counseling.

Topics: Child; Diagnosis, Differential; Female; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Nephrocalcinosis; Oxalates; Radiography

Oxalosis is a rare disorder, in which there are widely and evenly spread deposits of oxalate crystals in the kidneys with progressive renal failure. An inborn error of metabolism is the cause of oxalosis. The incidence of this disease in boys and girls is practically equal. Most patients do not survive their 20th year. In our case there were changes in the skeleton and extensive deposits of oxalates in the kidneys.

Topics: Child; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Male; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Radiography; Ureteral Calculi

The increased production and excretion of oxalate in primary hyperoxaluria causes urolithiasis, nephrocalcinosis with renal failure, and systemic oxalosis. Systemic oxalosis occurs late in the course of the disease when there is both oxalate retention and increased oxalate synthesis. The uraemia can be controlled by conventional haemodialysis or peritoneal dialysis but treatment cannot usually keep up with accelerated rate of oxalate production, and dialysed patients develop systemic oxalosis. Most attempts to treat primary hyperoxaluria by renal transplantation have been unsuccessful because of rapid recurrence of nephrocalcinosis with uraemia and systemic oxalosis. Dynamic studies of overall oxalate metabolism in vivo have shown that the renal retention factor becomes a major determinant of oxalosis when the GFR decreases to less than 25 ml min-1 1.73 m-2. We conclude provisionally that vigorous haemodialysis should be begun and transplantation arranged when the GFR reaches this level. Such early transplantation with vigorous perioperative haemodialysis and a large perioperative diuresis of water gives good immediate graft function and oxalate mobilisation from the miscible oxalate pool. The longer term outlook is then influenced more by the factors which determine the success of renal transplantation in non-hyperoxaluric patients.

Topics: Glomerular Filtration Rate; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Transplantation; Nephrocalcinosis; Oxalates; Oxalic Acid; Recurrence; Renal Dialysis

Primary hyperoxaluria is a rare metabolic disorder characterized by excessive synthesis and urinary excretion of oxalate. Nephrocalcinosis with or without calcium oxalate nephrolithiasis leads to renal failure in infancy through young adulthood. Oxalosis is the condition in which the highly insoluble calcium oxalate crystals are deposited in extrarenal tissues including bone, blood vessels, heart, and the male urogenital system. The radiographic abnormalities in 14 patients with primary hyperoxaluria are described. These abnormalities include nephrolithiasis, nephrocalcinosis, dense vascular calcifications, abnormal bone density, and characteristic metaphyseal abnormalities. Changes of renal osteodystrophy and pathologic fractures are common. Radiographic bone abnormalities are dependent on the age of the patient when renal failure occurred and the degree of success of renal transplantation. Characteristic skeletal changes are present in six of seven patients who developed renal failure when less than 7 years of age.

Topics: Adolescent; Adult; Calcinosis; Child; Child, Preschool; Female; Fractures, Spontaneous; Humans; Infant; Kidney Calculi; Male; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Radiography; Vascular Diseases

Topics: Adolescent; Calcium Oxalate; Child, Preschool; Female; Humans; Kidney Calculi; Male; Nephrocalcinosis; Oxalates; Oxalic Acid; Radiography

Two Arab siblings with nephrocalcinosis and renal failure secondary to primary hyperoxaluria are presented. Percutaneous renal biopsies obtained from both siblings showed marked oxalate deposition in the renal medulla. Primary hyperoxaluria should be considered in the differential diagnosis of renal failure in infancy and early childhood especially when evidence of obstructive uropathy is lacking.

Topics: Child, Preschool; Humans; Male; Nephrocalcinosis; Oxalates; Ultrasonography

Topics: Acute Kidney Injury; Humans; Infant; Kidney; Male; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Ultrasonography; Urography

Topics: Adolescent; Calcium; Child; Child, Preschool; Humans; Nephrocalcinosis; Oxalates; Oxalic Acid; Pyridoxine

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

Six out of seven patients with primary hyperoxaluria showed various degrees of oxalosis. The radiographic manifestations differ between patients younger than 15 years and those older than 45 years. The mild manifestations in children, only urolithiasis, can be explained by the, as yet, unimpaired renal function. The renal function in the older patients, with extensive pathologic changes like nephrocalcinosis, urolithiasis, soft-tissue calcification, and osseous changes, is very poor. The findings of extensive soft-tissue calcification and the bony changes are not in complete agreement with those in the literature.

Topics: Adolescent; Adult; Age Factors; Calcinosis; Humans; Kidney Diseases; Middle Aged; Nephrocalcinosis; Oxalates; Radiography; Urinary Calculi

Renal failure secondary to oxalate interstitial nephritis developed in three patients with malabsorption and steatorrhea following a jejunoileal bypass, extensive small intestine resection and a partial gastrectomy. Hyperoxaluria was documented in two of the cases. The possibility that this complication can occur in patients after a jejunoileal bypass operation is now recognized. This report shows that it can also occur in patients with other bowel disorders that cause malabsorption and steatorrhea. Since the prognosis for patients with oxalate nephropathy is poor, renal function should be closely monitored in patients who are at risk because of these disorders. Therapy should be directed at correcting malabsorption, steatorrhea and hyperoxaluria. When the renal function of patients with a jejunoileal bypass continues to decline despite intensive medical therapy, restoration of bowel continuity is strongly recommended.

Topics: Female; Gastrectomy; Gastrointestinal Diseases; Humans; Kidney Calculi; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Nephrocalcinosis; Oxalates; Postoperative Complications

In summary it can be stated that clinically and radiologically, nephrolithiasis und nephrocalcinosis are not uncommonly encountered together. It is the aim of x-ray diagnostic to detect stones and parenchymal calcification, to assess localisation, size and numer or extent, to recognise secondary changes in the renal parenchyma and urinary-tract resulting from stones and to aid the search for the primary disease. In addition there are readiographic methods valuable for the initiation of treatment, e. g. percutaneous antegrade pyelography and nephrostomy.

Topics: Adolescent; Glomerulonephritis; Humans; Hypercalcemia; Hyperparathyroidism; Kidney Calculi; Kidney Cortex Necrosis; Kidney Diseases; Male; Metabolic Diseases; Nephrocalcinosis; Oxalates; Phenacetin; Radiography

The clinical, pathologic and roentgenographic features of a case of congenital oxalosis are discussed and contrasted to the more common forms of primary oxalosis. The ease of demonstration of the cortical deposition of calcium oxalate crystals on the CT scanner is reported.

Topics: Amino Acid Metabolism, Inborn Errors; Female; Glycolates; Humans; Infant; Kidney Cortex; Nephrocalcinosis; Oxalates; Tomography, X-Ray Computed

Topics: Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Infant; Kidney Calculi; Male; Metabolic Diseases; Nephrocalcinosis; Oxalates; Radiography

Seventy-seven patients with nephrocalcinosis as revealed by X-ray studies over a 10-year period are reviewed. A programmed clinical and metabolic study was performed on each case; the author's criteria included the different pathogenic factors considered in the etiologic definition of the disease. There were 22 cases with primary hyperparathyroidism, 19 with spongy kidney, nine with tubulointerstitial nephropathy, five with hyperoxaluria, five with distal renal tubular acidosis, four with esential hypomagnesemia, and three cases of miscellaneous etiology (vitamin D intoxication, Fanconi's syndrome, Bartter's disease). Ten other cases were classified as idiopathic nephrocalcinosis since no definite cause could be found. The clinical characteristics (symptoms, associated diseases, diet and medication intake, family history) and the biochemical findings are analysed for each group. The physiopathologic mechanisms, comparisons between each etiologic group, treatment, clinical course, and prognosis are commented on. The conclusion drawn is that nephrocalcinosis is a clinical syndrome of various etiologies which in most cases arises from an underlying metabolic disease.

Topics: Acidosis, Renal Tubular; Bartter Syndrome; Fanconi Syndrome; Humans; Hyperparathyroidism; Magnesium Deficiency; Medullary Sponge Kidney; Metabolic Diseases; Neoplasm Metastasis; Nephritis, Interstitial; Nephrocalcinosis; Oxalates; Radiography; Vitamin D

Topics: Crystallization; Diagnosis, Differential; Humans; Infant; Kidney Diseases; Male; Nephrocalcinosis; Oxalates; Radiography

The clinical features of eight cases of primary hyperoxaluria have been summarized. The possibility of different phenotypes is discussed. A reduction, but no normalization, of the oxalate formation during pyridoxine therapy was found. A renal transplantation performed in one of the patients failed because of the formation of nephrocalcinosis.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Follow-Up Studies; Glycolates; Glyoxylates; Humans; Infant; Kidney Calculi; Male; Middle Aged; Nephrocalcinosis; Oxalates; Pedigree; Uremia; Ureteral Calculi

The authors report a case of regional enteritis complicated by nephrocalcinosis and nephrolithiasis. Enteric hyperoxaluria is documented and the pathophysiology is discussed.

Topics: Adult; Crohn Disease; Humans; Kidney Calculi; Middle Aged; Nephrocalcinosis; Oxalates; Radiography; Recurrence

Topics: Arrhythmias, Cardiac; Barbiturates; Butyrylcholinesterase; Drug Synergism; Drug Tolerance; Dysautonomia, Familial; Genetic Diseases, Inborn; Humans; Hyperbilirubinemia, Hereditary; Jaundice; Kidney Calculi; Malignant Hyperthermia; Metabolism, Inborn Errors; Narcotics; Nephrocalcinosis; Osteogenesis Imperfecta; Oxalates; Paralyses, Familial Periodic; Pharmacogenetics; Porphyrias; Succinylcholine

An experimental electron-microscopic study of the kidneys was carried out in experimental oxamide nephrolithiasis in rabbits and hypervitaminosis D in rats. The most pronounced changes were revealed in the proximal and the distal convoluted tubules. It is suggested that cytosomes and lysosome-like bodies possibly participated in stone formation and nephrocalcinosis. It is supposed that they played an important role in the morphogenesis of nephrolithiasis man.

Topics: Animals; Ergocalciferols; Kidney; Kidney Calculi; Male; Nephrocalcinosis; Oxalates; Rabbits; Rats

The radiological changes in a patient with endogenous oxalosis are correlated with their pathological and anatomical counterparts. These involve particulary the kidneys (nephrolithiasis, calcium oxalate nephrosis with scarring), the skeleton (combination of renal osteodystrophy, secondary hyperparathyroidism and oxalate deposition), and soft tissues (generalised oxalate deposition). The pathological aspects described in the literature are mentioned and possible forms of treatment are stressed.

Topics: Adult; Bone and Bones; Humans; Hyperparathyroidism; Kidney Calculi; Kidney Diseases; Metabolic Diseases; Nephrocalcinosis; Nephrosclerosis; Nephrosis; Oxalates; Radiography

The diangosis, clinical manifestations and management of 11 children with nephrocalcinosis encountered in a 20-year period are presented. Renal tubular acidosis, primary hyperoxaluria, primary hyperparathyroidism, exogenous hyperadrenocorticism and idiopathic hypercalcemia of infancy were the principal causes of nephrocalcinosis in this series. In the presence of normal or near-normal renal function, a 55 per cent or better cure rate can be expected. Children with significantly diminished renal function have a poor prognosis and should be considered for renal transplantation.

Topics: Acidosis, Renal Tubular; Adolescent; Child; Child, Preschool; Cushing Syndrome; Female; Humans; Hypercalcemia; Hyperparathyroidism; Kidney Calculi; Kidney Transplantation; Male; Nephrocalcinosis; Oxalates; Prognosis; Transplantation, Homologous; Ureteral Calculi

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

Topics: Acidosis, Renal Tubular; Adrenal Gland Diseases; Adrenal Glands; Adrenalectomy; Calcium; Female; Humans; Hyperaldosteronism; Hypokalemia; Middle Aged; Nephrocalcinosis; Oxalates; Phosphates; Potassium; Recurrence; Sodium; Urinary Calculi

Topics: Biopsy; Cadaver; Child, Preschool; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Peritoneal Dialysis; Transplantation, Homologous

Topics: Amides; Animals; Diet; Female; Ischemia; Kidney; Kidney Calculi; Ligation; Male; Microscopy, Electron, Scanning; Nephrocalcinosis; Oxalates; Rabbits; Renal Artery; Renal Veins

Topics: Adolescent; Adult; Aged; Biopsy; Calcium; Child; Child, Preschool; Colonic Neoplasms; Cystine; Epithelial Cells; Female; Humans; Hyperparathyroidism; Kidney Calculi; Kidney Tubules, Distal; Male; Middle Aged; Nephrocalcinosis; Nephrons; Oxalates; Peptic Ulcer; Phosphates; Uric Acid; Urinary Tract Infections

Topics: Acute Kidney Injury; Adult; Arterial Occlusive Diseases; Autopsy; Coronary Vessels; Female; Humans; Metabolic Diseases; Nephrocalcinosis; Oxalates; Peritoneal Dialysis; Plethysmography; Uremia

Topics: Adolescent; Autopsy; Calcium; Cerebral Arteries; Child; Female; Histocytochemistry; Humans; Kidney; Male; Metabolism, Inborn Errors; Myocardium; Nephrocalcinosis; Oxalates; Pedigree; Ureter

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

Topics: Animals; Avitaminosis; Calcium; Chromatin; Cytoplasm; Endoplasmic Reticulum; Epithelial Cells; Golgi Apparatus; Kidney; Kidney Tubules; Lipids; Male; Microscopy, Electron; Mitochondria; Nephrocalcinosis; Oxalates; Pyridoxine; Rats; Rats, Inbred Strains; Ribosomes; Time Factors

Topics: Acidosis, Renal Tubular; Adult; Calcium; Cystinuria; Diphosphates; Female; Humans; Hyperparathyroidism; Male; Nephrocalcinosis; Oxalates; Peptides; Urinary Bladder Calculi

Topics: Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Child; Female; Glyoxylates; Humans; Kidney Calculi; Magnesium Oxide; Nephrocalcinosis; Oxalates; Recurrence

Topics: Adolescent; Adult; Alcohol Oxidoreductases; Child; Glycolates; Glyoxylates; Humans; Kidney; Ligases; Liver; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Oxidoreductases; Urinary Calculi; Vitamin B 6 Deficiency; Xanthine Oxidase

Topics: Adult; Aged; Calcium; Female; Humans; Kidney Calculi; Male; Middle Aged; Nephrocalcinosis; Oxalates

Topics: Adult; Aged; Aorta; Autopsy; Child; Female; Glycols; Humans; Kidney Calculi; Male; Metabolic Diseases; Myocardium; Nephrocalcinosis; Nephrosis; Oxalates; Pulmonary Alveoli; Spine; Spleen; Thyroid Gland

Topics: Adult; Blood Vessels; Cardiomyopathies; Female; Heart Conduction System; Humans; Kidney Calculi; Male; Metabolic Diseases; Nephrocalcinosis; Oxalates; Pregnancy; Renal Dialysis

Topics: Adult; Calcium; Child; Child, Preschool; Female; Glyoxylates; Humans; Kidney; Kidney Calculi; Male; Middle Aged; Nephrocalcinosis; Oxalates

Topics: Adult; Child; Chromatography; Colorimetry; Female; Glyceric Acids; Humans; Kidney Calculi; Male; Metabolism, Inborn Errors; Methods; Nephrocalcinosis; Optical Rotatory Dispersion; Oxalates

Topics: Adolescent; Adult; Allopurinol; Child; Child, Preschool; Female; Humans; Kidney Calculi; Male; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates

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: Adult; Humans; Kidney; Kidney Diseases; Male; Nephritis, Interstitial; Nephrocalcinosis; Oxalates; Renal Tubular Transport, Inborn Errors

Topics: Adolescent; Child; Female; Humans; Kidney; Kidney Calculi; Male; Nephrocalcinosis; Oxalates; Radiography

Topics: Adolescent; Adult; Child; Female; Humans; Male; Metabolism, Inborn Errors; Middle Aged; Nephrocalcinosis; Nutrition Disorders; Oxalates; Vitamin D

Topics: Animals; Carbonic Anhydrase Inhibitors; Male; Nephrocalcinosis; Oxalates; Rats; Vitamin D

Topics: Humans; Infant; Kidney Diseases; Male; Nephrocalcinosis; Oxalates; Urine

Topics: Adult; Female; Humans; Kidney Calculi; Metabolic Diseases; Nephrocalcinosis; Oxalates

Topics: Humans; Hyperoxaluria; Metabolic Diseases; Nephrocalcinosis; Oxalates; Pyelonephritis; Toxicology

Topics: Consanguinity; Heart Block; Humans; Hyperoxaluria; Kidney Calculi; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates; Pancreatitis; Pathology; Skin Diseases; Uremia; Urine

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Carbon Isotopes; Family; Glycine; Glycolates; Glyoxylates; Hippurates; Humans; Hydroxyproline; Kidney Calculi; Nephrocalcinosis; Oxalates; Urine

Topics: Adult; Humans; Male; Metabolism, Inborn Errors; Nephrocalcinosis; Oxalates

Topics: Benzoates; Child; Diet; Diet Therapy; Genetics, Medical; Humans; Hyperoxaluria, Primary; Kidney Calculi; Metabolic Diseases; Nephrocalcinosis; Oxalates; Surgical Procedures, Operative; Urine; Urography

Topics: Body Fluids; Glyoxylates; Humans; Hyperoxaluria, Primary; Keto Acids; Kidney Calculi; Metabolic Diseases; Nephrocalcinosis; Oxalates; Urine

Topics: Genetics, Medical; Humans; Hyperoxaluria; Metabolic Diseases; Nephrocalcinosis; Oxalates

Topics: Animals; Calcium Oxalate; Ethylene Glycol; Ethylenes; Glycols; Kidney; Nephrocalcinosis; Oxalates; Rats

Topics: Calcium Oxalate; Humans; Hyperoxaluria, Primary; Kidney Diseases; Nephrocalcinosis; Oxalates

Topics: Animals; Calculi; Cats; Kidney; Kidney Calculi; Nephrocalcinosis; Oxalates; Vitamin B 6 Deficiency; Vitamin B Deficiency; Vitamins

Topics: Humans; Hyperoxaluria, Primary; Kidney Diseases; Nephrocalcinosis; Oxalates

Topics: Child; Dwarfism; Humans; Hyperoxaluria; Infant; Kidney; Medical Records; Metabolic Diseases; Nephrocalcinosis; Oxalates; Renal Insufficiency

Topics: Calcium Oxalate; Calculi; Humans; Kidney; Kidney Calculi; Nephrocalcinosis; Nephrolithiasis; Oxalates

Topics: Calcification, Physiologic; Calcinosis; Kidney Diseases; Nephrocalcinosis; Oxalates

Topics: Calcium Oxalate; Humans; Hyperoxaluria; Nephrocalcinosis; Nephrolithiasis; Oxalates