oxalates and Nephrolithiasis

Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.

Topics: Diabetes Mellitus, Type 2; Humans; Hyperoxaluria, Primary; Hypertension; Kidney; Nephrolithiasis; Oxalates

Nephrolithiasis is the most common type of urinary system disease in developed countries, with high morbidity and recurrence rates. Nephrolithiasis is a serious health problem, which eventually leads to the loss of renal function and is closely related to hypertension. Modern medicine has adopted minimally invasive surgery for the management of kidney stones, but this does not resolve the root of the problem. Thus, nephrolithiasis remains a major public health issue, the causes of which remain largely unknown. Researchers have attempted to determine the causes and therapeutic targets of kidney stones and calculus‑related hypertension. Solute carrier family 26 member 6 (SLC26A6), a member of the well‑conserved solute carrier family 26, is highly expressed in the kidney and intestines, and it primarily mediates the transport of various anions, including OXa

Topics: Citrates; Dicarboxylic Acid Transporters; Hyperoxaluria; Hypertension; Intestines; Kidney; Kidney Calculi; Membrane Transport Proteins; Nephrolithiasis; Organic Anion Transporters, Sodium-Dependent; Oxalates; Sulfate Transporters; Symporters

Oxalobacter formigenes, a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by

Topics: Animals; Gastrointestinal Microbiome; Genomics; Humans; Inactivation, Metabolic; Metabolomics; Nephrolithiasis; Oxalates; Oxalobacter formigenes

Oxalate is both a plant-derived molecule and a terminal toxic metabolite with no known physiological function in humans. It is predominantly eliminated by the kidneys through glomerular filtration and tubular secretion. Regardless of the cause, the increased load of dietary oxalate presented to the kidneys has been linked to different kidney-related conditions and injuries, including calcium oxalate nephrolithiasis, acute and chronic kidney disease. In this paper, we review the current literature on the association between dietary oxalate intake and kidney outcomes.

Topics: Animals; Diet; Disease Models, Animal; Glomerular Filtration Rate; Humans; Kidney; Nephrolithiasis; Oxalates; Randomized Controlled Trials as Topic

Kidney stone disease is increasing in prevalence, and the most common stone composition is calcium oxalate. Dietary oxalate intake and endogenous production of oxalate are important in the pathophysiology of calcium oxalate stone disease. The impact of dietary oxalate intake on urinary oxalate excretion and kidney stone disease risk has been assessed through large cohort studies as well as smaller studies with dietary control. Net gastrointestinal oxalate absorption influences urinary oxalate excretion. Oxalate-degrading bacteria in the gut microbiome, especially

Topics: Bacteria; Calcium Oxalate; Diet; Gastrointestinal Microbiome; Humans; Kidney; Kidney Calculi; Nephrolithiasis; Oxalates; Oxalobacter formigenes; Urolithiasis

Nephrolithiasis is a condition marked by the presence or formation of stones in kidneys. Several factors contribute to kidney stones development such as environmental conditions, type of dietary intake, gender and gastrointestinal flora. Most of the kidney stones are composed of calcium phosphate and calcium oxalate, which enter in to the body through diet. Both sources of oxalates become dangerous when normal flora of gastrointestinal tract is disturbed. Oxalobacter and Lactobacillus species exist symbiotically in the human gut and prevent stone formation by altering some biochemical pathways through production of specific enzymes which help in the degradation of oxalate salts. Both Oxalobacter and Lactobacillus have potential probiotic characteristics for the prevention of kidney stone formation and this avenue should be further explored.

Topics: Calcium; Calcium Oxalate; Calcium Phosphates; Diet; Dietary Supplements; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Kidney Calculi; Lactobacillus; Nephrolithiasis; Oxalates; Oxalobacter formigenes; Probiotics

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

Primary hyperoxalurias (PH) comprise a group of three distinct metabolic diseases caused by derangement of glyoxylate metabolism in the liver. Recent years have seen advances in several aspects of PH research. This paper reviews current knowledge of the genetic and biochemical basis of PH, the specific epidemiology and clinical presentation of each type, and therapeutic approaches in different disease stages. Potential future specific therapies are discussed.

Topics: Genetic Predisposition to Disease; Genetic Testing; Humans; Hyperoxaluria, Primary; Mutation; Nephrolithiasis; Oxalates; Renal Replacement Therapy; Transaminases

Oxalobacter formigenes is a unique intestinal organism that relies on oxalate degradation to meet most of its energy and carbon needs. A lack of colonization is a risk factor for calcium oxalate stone disease. Protection against calcium oxalate stone disease appears to be due to the oxalate degradation that occurs in the gut on low calcium diets with a possible further contribution from intestinal oxalate secretion. Much remains to be learned about how the organism establishes and maintains gut colonization and the precise mechanisms by which it modifies stone risk. The sequencing and annotation of the genomes of a Group 1 and a Group 2 strain of O. formigenes should provide the informatic tools required for the identification of the genes and pathways associated with colonization and survival. In this review we have identified genes that may be involved and where appropriate suggested how they may be important in calcium oxalate stone disease. Elaborating the functional roles of these genes should accelerate our understanding of the organism and clarify its role in preventing stone formation.

Topics: Animals; Anti-Bacterial Agents; Calcium Oxalate; Diet; Genome, Bacterial; Humans; Intestinal Mucosa; Intestines; Microbiota; Nephrolithiasis; Oxalates; Oxalobacter formigenes; Probiotics; Risk Factors; Symbiosis

Microorganisms are one of the important factors for urinary calculi formation. While urease-positive bacteria and nanobacteria contribute to stone formation, Oxalobacter formigenes rods play a protective role against the development of urolithiasis. Proteus mirabilis alkaline environment of the urinary tract and cause crystallization mainly of struvite (magnesium ammonium phosphate). However, nanobacteria, due to the possibility of apatite deposition on the surface of their cells, have long been considered as an etiological factor of urinary calculi consisting of calcium phosphates. O. formigenes is an anaerobe using oxalate as the main source of carbon and energy and occurs as natural gastrointestinal microflora of humans and animals. These bacteria control the amount of oxalate excretion degrading oxalates and regulating their transport by intestinal epithelium. Lower colonization of the human colon by O. formigenes can cause increased oxalate excretion and lead to the development of oxalate urolithiasis. Due to the positive influence of O. formigenes, there is ongoing research into the use of this microorganism as a probiotic in the prophylaxis or treatment of hyperoxaluria, both secondary and primary. The results of these studies are very promising, but they still require continuation. Future studies focus on the exact characteristics of O. formigenes including their metabolism and the development of methods for applying as a therapeutic agent the bacteria or their enzymes degrading the oxalate.

Topics: Animals; Calcium Oxalate; Crystallization; Humans; Hyperoxaluria; Intestinal Mucosa; Magnesium Compounds; Nephrolithiasis; Oxalates; Oxalobacter formigenes; Phosphates; Probiotics; Proteus mirabilis; Struvite; Urease

The majority of the Na(+) and Cl(-) filtered by the kidney is reabsorbed in the proximal tubule. In this nephron segment, a significant fraction of Cl(-) is transported via apical membrane Cl(-)-base exchange: Cl(-)-formate exchange, Cl(-)-oxalate exchange, Cl(-)-OH(-) exchange, and Cl(-)-HCO(3)(-) exchange. A search for the transporter responsible for apical membrane Cl(-)-formate exchange in the proximal tubule led to the identification of CFEX (SLC26A6). Functional expression studies in Xenopus oocytes demonstrated that CFEX is capable of mediating not only Cl(-)-formate exchange but also Cl(-)-oxalate exchange, Cl(-)-OH(-) exchange, and Cl(-)-HCO(3)(-) exchange. Studies in CFEX-null mice have begun to elucidate which of the anion exchange activities mediated by CFEX is important for renal physiology and pathophysiology in vivo. Measurements of transport in renal brush border vesicles isolated from CFEX-null mice demonstrated that CFEX primarily mediates Cl(-)-oxalate exchange rather than Cl(-)-formate exchange. Microperfusion studies in CFEX-null mice revealed that CFEX plays an essential role in mediating oxalate-dependent NaCl absorption in the proximal tubule. CFEX-null mice were found to have hyperoxaluria and a high incidence of calcium oxalate urolithiasis. The etiology of hyperoxaluria in CFEX-null mice was observed to be a defect in oxalate secretion in the intestine, leading to enhanced net absorption of ingested oxalate and elevation of plasma oxalate. Thus, by virtue of its function as a Cl(-)-oxalate exchanger, CFEX plays essential roles both in proximal tubule NaCl transport and in the prevention of hyperoxaluria and calcium oxalate nephrolithiasis.

Topics: Animals; Antiporters; Calcium Oxalate; Chloride-Bicarbonate Antiporters; Chlorides; Disease Models, Animal; Formates; Homeostasis; Humans; Hyperoxaluria; Immunohistochemistry; Intestinal Absorption; Ion Exchange; Kidney Tubules, Proximal; Mice; Mice, Knockout; Models, Biological; Nephrolithiasis; Oocytes; Oxalates; Sodium Chloride; Sulfate Transporters; Xenopus

Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n = 5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion.. Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels.. The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p = 0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day).. Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.

Topics: Adult; Ascorbic Acid; Dietary Supplements; Female; Humans; Male; Nephrolithiasis; Oxalates; Plant Preparations; Renal Elimination; Risk Factors; Vaccinium macrocarpon; Vitamins; Young Adult

Epidemiological data indicate an increasing incidence and prevalence of nephrolithiasis (NL) worldwide in the last few decades.. The aim of this study was to compare the clinical and biochemical profiles of recurrent stone formers referred to a Kidney Stone Centre from March 1983 to June 1986 with the one featured by patients seen 25 years later in the same geographical area, Campania, southern Italy.. Idiopathic calcium stone formers made up the large majority of the patient population in both series. Those examined in 2008-11 showed higher age at the onset of NL, higher prevalence of overweight/obesity and higher urinary excretion of oxalate and phosphate compared with those seen in 1983-86. The differences in the urinary biochemical variables remained significant upon accounting for age, gender, creatinine clearance and body mass index (BMI), and were not observed in patients with primary hyperparathyroidism enrolled in the same periods. A greater prevalence of uric acid stone formers was also observed in the 2008-11 population.. The massive epidemics of overweight/obesity and the substantial modifications of dietary habits over the last few decades in most Western countries may be the factors underlying the changing clinical and biochemical profiles of patients with recurrent NL.

Topics: Adult; Biomarkers; Body Mass Index; Calcium; Female; Humans; Male; Nephrolithiasis; Obesity; Overweight; Oxalates; Uric Acid

We tested the hypothesis that the cationic phosphate binder sevelamer hydrochloride could reduce hyperoxaluria and calcium oxalate supersaturation in patients with enteric hyperoxaluria by binding fatty acids, binding phosphate and rendering calcium free to bind oxalate, and/or directly binding oxalate. A secondary objective was to assess changes in the urinary excretion of other substances associated with nephrolithiasis.. Ten patients with enteric hyperoxaluria were enrolled in a nonrandomized, open label trial of sevelamer hydrochloride (3,200 mg 3 times daily for 7 days).. With treatment mean urinary oxalate decreased 17% (0.84 to 0.70 mmol per day) and the urinary oxalate-to-creatinine ratio decreased 11% (0.055 to 0.049 mmol/mmol, p not significant for both). Urinary calcium increased 25% (p not significant). Urinary citrate decreased 23% (p = 0.01) and urinary phosphorus decreased 44% (p = 0.0001). Mean supersaturation of calcium oxalate, brushite, hydroxyapatite, uric acid and sodium urate did not change significantly. However, the decrease in brushite supersaturation approached statistical significance (p = 0.07). Mean serum phosphorus was 3.6 mg/dl at baseline and 3.3 mg/dl with therapy (p not significant). Hypophosphatemia did not develop in any patients. One patient dropped out of study due to abdominal pain.. Sevelamer hydrochloride dramatically decreased urinary phosphorus excretion with a lesser effect on urinary oxalate. Supersaturation of calcium oxalate did not decrease due to countervailing effects on other constituents including an increase in urinary calcium and a decrease in urinary citrate. Although sevelamer hydrochloride may not be an ideal agent for correcting hyperoxaluria, its potential to reduce calcium phosphate supersaturation merits further investigation.

Topics: Adult; Calcium Oxalate; Chelating Agents; Female; Humans; Hyperoxaluria; Male; Middle Aged; Nephrolithiasis; Oxalates; Phosphorus; Pilot Projects; Polyamines; Sevelamer

Patients treated for obesity with jejunoileal bypass (JIB) experienced a marked increased risk of hyperoxaluria, nephrolithiasis, and oxalate nephropathy developing. Jejunoileal bypass has been abandoned and replaced with other options, including Roux-en-Y gastric bypass (RYGB). Changes in urinary lithogenic risk factors after RYGB are currently unknown. Our purpose was to determine whether RYGB is associated with elevated risk of developing calcium oxalate stone formation through increased urinary oxalate excretion and relative supersaturation of calcium oxalate.. A prospective longitudinal cohort study of 24 morbidly obese adults (9 men and 15 women) recruited from a university-based bariatric surgery clinic scheduled to undergo RYGB between December 2005 and April 2007. Patients provided 24-hour urine collections for analysis 7 days before and 90 days after operation. Primary outcomes were changes in 24-hour urinary oxalate excretion and relative supersaturation of calcium oxalate from baseline to 3 months post-RYGB.. Compared with their baseline, patients undergoing RYGB had increased urinary oxalate excretion (31 +/- 10 mg/d versus 41 +/- 18 mg/d; p = 0.026) and relative supersaturation of calcium oxalate (1.73 +/- 0.81 versus 3.47 +/- 2.59; p = 0.030) 3 months post-RYGB in six patients (25%). De novo hyperoxaluria developed. There were no preoperative patient characteristics predictive of development of de novo hyperoxaluria or the magnitude of change of daily oxalate excretion.. This prospective study indicates that RYGB is associated with an earlier increase in urinary oxalate excretion and relative supersaturation of calcium oxalate than previously reported. Additional studies are needed to determine longterm post-RYGB changes in urinary oxalate excretion and identify patients that might be at risk for hyperoxaluria developing.

Topics: Adult; Calcium Oxalate; Cohort Studies; Female; Gastric Bypass; Humans; Hyperoxaluria; Longitudinal Studies; Male; Middle Aged; Nephrolithiasis; Obesity; Oxalates; Prospective Studies; Risk Factors

Topics: Animals; Ferroptosis; Glycogen Synthase Kinase 3 beta; Inflammation; Nephrolithiasis; NF-E2-Related Factor 2; Oxalates; Rats; Rats, Sprague-Dawley

Nephrolithiasis (NL) is a complex multifactorial disease affecting up to 10%-20% of the human population and causing a significant burden on public health systems worldwide. It results from a combination of environmental and genetic factors. Hyperoxaluria is a major risk factor for NL.. We used a whole exome-based approach in a patient with calcium oxalate NL. The effects of the mutation were characterised using cell culture and in silico analyses.. We identified a rare heterozygous missense mutation (c.1519C>T/p.R507W) in the. Our study is in line with previous observations made in the mouse showing that

Topics: Antiporters; Calcium; Calcium Oxalate; Humans; Hyperoxaluria; Mutation; Nephrolithiasis; Oxalates; Sulfate Transporters

Meals rich in oxalate are associated with calcium oxalate (CaOx) kidney stone disease. Hydroxy-L-proline (HLP) is an oxalate precursor found in milk and collagen-containing foods. HLP has been shown to induce CaOx crystal formation in rodents. The purpose of this study was to evaluate the effect of HLP induced oxalate levels on inflammation and renal leukocytes during crystal formation. Male Sprague-Dawley rats (6-8 weeks old) were fed a control diet containing no oxalate for 3 days before being randomized to continue the control diet or 5% HLP for up to 28 days. Blood, 24 h urine, and kidneys were collected on Days 0, 7, 14, or 28. Urinary oxalate levels, crystal deposition, and renal macrophage markers were evaluated using ion chromatography-mass spectrometry, immunohistochemistry, and qRT-PCR. Renal leukocytes were assessed using flow cytometry and RNA-sequencing. HLP feeding increased urinary oxalate levels and renal crystal formation in animals within 7 days. HLP also increased renal macrophage populations on Days 14 and 28. Transcriptome analysis revealed that renal macrophages from animals fed HLP for 7 days were involved in inflammatory response and disease, stress response to LPS, oxidative stress, and immune cell trafficking. Renal macrophages isolated on Day 14 were involved in cell-mediated immunological pathways, ion homeostasis, and inflammatory response. Collectively, these findings suggest that HLP-mediated oxalate levels induce markers of inflammation, leukocyte populations, and reprograms signaling pathways in macrophages in a time-dependent manner. Additional studies investigating the significance of oxalate on renal macrophages could aid in our understanding of kidney stone formation.

Topics: Animals; Calcium Oxalate; Hydroxyproline; Inflammation; Kidney Calculi; Macrophages; Male; Nephrolithiasis; Oxalates; Rats; Rats, Sprague-Dawley

Medically complex, non-ambulatory children can often suffer from nephrolithiasis. The purpose of this study is to determine risk factors which are predictive for recurrent stone formation in this patient population.. A retrospective cohort study was performed on non-ambulatory patients with cerebral palsy and/or severe developmental delay presenting to a high-volume Pediatric Stone Center from 2015 to 2019. Two 24-hour urine collections were performed as a baseline prior to pharmacotherapeutic and/or dietary intervention. Healthy stone-forming children served as a control group.. Urinary oxalate excretion is significantly increased in a cohort of medically complex, non-ambulatory stone-forming children. Urinary calcium excretion was not elevated between study subjects and healthy controls. Further analysis is needed to assess if dietary intervention to limit oxalate excretion results in decreased stone formation.

Topics: Calcium; Calcium Oxalate; Child; Enteral Nutrition; Humans; Kidney Calculi; Nephrolithiasis; Oxalates; Retrospective Studies

American Urology Association guidelines recommend genetic testing for patients with recurrent stones and urine oxalate > 75 mg/day. The goal of this study was to examine the treatment of patients in this category in a large multidisciplinary adult stone clinic.. Patients were evaluated from a single institution between 2006 and 2019. Those with at least one level of urinary oxalate excretion (uOx) above 75 mg/day were identified. A chart review identified enteric risk factors and genetic testing results. Patients without an identifiable enteric cause were considered idiopathic.. A total of 4229 separate 24-h urine collections in 1302 patients were reviewed. At least one measurement of uOx above 75 mg/day was found in 103 (7.9%) patients. Enteric hyperoxaluria (EH) was seen in 28 (27%) and idiopathic hyperoxaluria (IH) in 76 (74%). 20 (71%) patients in the EH group had undergone gastric bypass. The median uOx was significantly higher level in the EH group (121.0 vs. 93.0 mg/day). For the entire cohort, there was a drop in uOx (- 33.8 mg/day) with medical and dietary therapy after a follow-up of 46.6 months. The final oxalate was higher in EH (88.9 vs. 60.1 mg/day). Only one patient had referral for genetic testing and was found to have primary hyperoxaluria type 2.. The most common cause of significant hyperoxaluria in patients with recurrent nephrolithiasis remains idiopathic. Patients with IH have more significant improvement in uOx compared to EH; however, both groups had hyperoxaluria at last follow-up. Rate of genetic testing is low despite guideline recommendations.

Topics: Adult; Cohort Studies; Humans; Hyperoxaluria; Kidney Calculi; Nephrolithiasis; Oxalates; Risk Factors

Oxalate and citrate in 24 h urine and serum are considered to be associated with the incidence and recurrence risk of calcium oxalate kidney stones. The quantification of oxalate and citrate contributes to understand the pathological metabolism of kidney stones and guide the early diagnosis and recurrence monitoring. Although simultaneous quantification of oxalate and citrate in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS) have been reported, the optimization of chromatographic column, mobile phase and mass spectrometry (MS) parameters has not been performed. In addition, these is a lack of suitable method for simultaneous detection of oxalate and citrate both in serum and urine. Therefore, we developed a method for the simultaneous determination of oxalate and citrate in urine and serum based on ion-pairing reversed-phase (IP-RP) LC-MS/MS. Herein, five ion-pair reagents, namely, triethanolamine, dimethylbutyl amine, diisopropenyl amine, N,N-dimethylcyclohexylamine and tripropylamine, and three ion-pairing reagent (IPR) buffers, namely, acetic acid, hexafluoro-2-isopropanol, and hexafluoro-2-methyl-2-propanol, were compared in regard to their chromatographic peak abundance and separation of oxalate and citrate. Moreover, MS parameters and the multiple reaction monitoring (MRM) conditions were also evaluated and optimized to obtain the maximum peak abundance. After that, the method was validated in the linear range of 0.25-1000 µM, and the correlation coefficient was ≥ 0.99. The precision and accuracy were < 14.70% and < 19.73%, respectively. The extraction recovery was 80.53-108.79%, and the matrix effect was < 8.79%. The quality control samples were stable at room temperature for 4 h, 4 °C for 24 h, and for 3 freeze-thaw cycles. Finally, this method was applied to the determination of oxalate and citrate in the serum and urine of rats with calcium oxalate kidney stones. The establishment of a stable and effective oxalate and citrate detection method is conducive to the diagnosis and monitoring of kidney stones.

Topics: Amines; Animals; Calcium Oxalate; Chromatography, Liquid; Citric Acid; Ions; Kidney Calculi; Nephrolithiasis; Oxalates; Rats; Tandem Mass Spectrometry

Oxidative stress, a well-known cause of stress-induced premature senescence (SIPS), is increased in patients with calcium oxalate (CaOx) kidney stones (KS). Oxalate and calcium oxalate monohydrate (COM) induce oxidative stress in renal tubular cells, but to our knowledge, their effect on SIPS has not yet been examined. Here, we examined whether oxalate, COM, or urine from patients with CaOx KS could induce SIPS and telomere shortening in human kidney (HK)-2 cells, a proximal tubular renal cell line. Urine from age- and sex-matched individuals without stones was used as a control. In sublethal amounts, H

Topics: Aged; Aging, Premature; Calcium Oxalate; Cell Line; Cyclin-Dependent Kinase Inhibitor p16; DNA Damage; Female; Humans; Hydrogen Peroxide; Male; Middle Aged; Nephrolithiasis; Oxalates; Oxidative Stress; Telomere Shortening; Telomeric Repeat Binding Protein 1

Calcium oxalate stones are the most common cause of nephrolithiasis in the United States. Smaller studies of <15 patients investigating ezetimibe, a selective cholesterol absorption inhibitor, have suggested increased urine oxalate levels with use of the drug. We attempt to better define this relationship of ezetimibe on urinary oxalate using a larger patient sample analysing multiple urine collections on and off treatment.. We retrospectively reviewed all consecutive patients from 01/2018 through 04/2019 evaluated for nephrolithiasis with use of ezetimibe documented in their medical record at Mayo Clinic Florida. Primary outcomes included increase in urinary oxalate with use of ezetimibe and reduction in urinary oxalate with discontinuation of medication.. Use of ezetimibe does not provide clear evidence of a difference in urinary oxalate levels.

Topics: Aged; Anticholesteremic Agents; Ezetimibe; Female; Humans; Male; Middle Aged; Negative Results; Nephrolithiasis; Oxalates; Retrospective Studies

Topics: Calcium Oxalate; Humans; Kidney Calculi; Nephrolithiasis; Oxalates; Renal Insufficiency, Chronic; Retrospective Studies

The anion exchanger SAT-1 [sulfate anion transporter 1 (Slc26a1)] is considered an important regulator of oxalate and sulfate homeostasis, but the mechanistic basis of these critical roles remain undetermined. Previously, characterization of the SAT-1-knockout (KO) mouse suggested that the loss of SAT-1-mediated oxalate secretion by the intestine was responsible for the hyperoxaluria, hyperoxalemia, and calcium oxalate urolithiasis reportedly displayed by this model. To test this hypothesis, we compared the transepithelial fluxes of

Topics: Animals; Antiporters; Chlorides; Homeostasis; Hyperoxaluria; Intestinal Mucosa; Intestines; Ion Transport; Kidney; Liver; Mice, Knockout; Nephrolithiasis; Oxalates; Sulfate Transporters

Monocytes/macrophages are thought to be recruited to the renal interstitium during calcium oxalate (CaOx) kidney stone disease for crystal clearance. Mitochondria play an important role in monocyte function during the immune response. We recently determined that monocytes in patients with CaOx kidney stones have decreased mitochondrial function compared to healthy subjects. The objective of this study was to determine whether oxalate, a major constituent found in CaOx kidney stones, alters cell viability, mitochondrial function, and redox homeostasis in THP-1 cells, a human derived monocyte cell line. THP-1 cells were treated with varying concentrations of CaOx crystals (insoluble form) or sodium oxalate (NaOx; soluble form) for 24h. In addition, the effect of calcium phosphate (CaP) and cystine crystals was tested. CaOx crystals decreased cell viability and induced mitochondrial dysfunction and redox imbalance in THP-1 cells compared to control cells. However, NaOx only caused mitochondrial damage and redox imbalance in THP-1 cells. In contrast, both CaP and cystine crystals did not affect THP-1 cells. Separate experiments showed that elevated oxalate also induced mitochondrial dysfunction in primary monocytes from healthy subjects. These findings suggest that oxalate may play an important role in monocyte mitochondrial dysfunction in CaOx kidney stone disease.

Topics: Adult; Calcium Phosphates; Cell Line; Cell Survival; Homeostasis; Humans; Kidney; Male; Mitochondria; Monocytes; Nephrolithiasis; Oxalates; Oxidation-Reduction

Nephrolithiasis is one of the most common urinary tract diseases. After the first episode of urinary calculus, the risk of recurrence is nearly 40% to 50% at 5 years. Nephrolithiasis is a systemic disease that is associated with some metabolic disorders. This study aimed to provide a picture of the frequency of metabolic abnormalities in patients with nephrolithiasis from west part of Iran.. Patients with recurrent urinary tract calculi referred to the Nephrology-Urology Clinics in Khorramabad city were recruited. After collection of demographic data of all the patients, 24-hour urine and blood samples were taken to measure biochemical factors.. Of the 232 participants, 125 were males and 107 were females. Hyperoxaluria was seen in 93 (40.1%) of the participants, hypercalciuria in 55 (23.7%), hypocitraturia in 58 (25%), and hyperuricosuria in 33 (14.9%). Hyperoxaluria in the males was significantly more frequent than in the female patients. There were no significant differences between the two groups in other urinary metabolic disorders.. Patients with nephrolithiasis from Lorestan province may have metabolic characteristics varying from those of regions; ethnicity may be a possible reason. Variation of dietary regimens, such as the amount of meat or vegetable in the diet that can change oxalate, calcium, or citrate of urine, might have influenced the results. Time of sampling is another factor. Population-specific studies are helpful to health care providers for preventive planning for nephrolithiasis.

Topics: Adult; Biomarkers; Calcium; Citrates; Cross-Sectional Studies; Female; Humans; Hypercalciuria; Hyperoxaluria; Iran; Male; Middle Aged; Nephrolithiasis; Oxalates; Recurrence; Risk Factors; Sex Distribution; Uric Acid; Urinalysis

Topics: Chromatography, Liquid; Citrates; Citric Acid; Humans; Nephrolithiasis; Oxalates; Tandem Mass Spectrometry

The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of. Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles.. Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.

Topics: Adult; Aged; Bacteria; Bacterial Typing Techniques; Biodiversity; Calcium Oxalate; Case-Control Studies; DNA, Bacterial; Energy Intake; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Metagenomics; Middle Aged; Nephrolithiasis; Oxalates; Recurrence; RNA, Ribosomal, 16S; Young Adult

To investigate the possible involvement of multidrug resistance-associated protein 1 (MRP-1) and breast cancer resistance protein (BCRP) in the oxalate-induced redistribution of phosphatidylserine (PS) in renal epithelial cell membranes.. A western blot analysis was used to examine the MRP-1 and BCRP expression levels. Surface-expressed PS was detected by the annexin V-binding assay. The cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate was used to measure the intracellular reactive oxygen species (ROS) level. A rat model of hyperoxaluria was obtained using 0.5% ethylene glycol and 1.0% ammonium chloride. In addition, certain animals received verapamil (50 mg/kg body weight), which is a common inhibitor of MRP-1 and BCRP. The degree of nephrolithiasis was assessed histomorphometrically using sections stained by Pizzolato method and by measuring the calcium oxalate crystal content in the renal tissue.. Oxalate produced a concentration-dependent increase in the synthesis of MRP-1 and BCRP. Treatment with MK571 and Ko143 (MRP-1- and BCRP-specific inhibitors, respectively) significantly attenuated the oxalate-induced PS externalization. Adding the antioxidant N-acetyl-l-cysteine significantly reduced MRP-1 and BCRP expression. In vivo, markedly decreased nephrocalcinosis was observed compared with that in the rat model of hyperoxaluria without verapamil treatment.. Oxalate induces the upregulation of MRP-1 and BCRP, which act as phospholipid floppases causing PS externalization in the renal epithelial cell membrane. The process is mediated by intracellular ROS production. The ROS-mediated increase in the synthesis of MRP-1 and BCRP can play an important role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 2; Blotting, Western; Cells, Cultured; Disease Models, Animal; Flow Cytometry; Immunohistochemistry; Male; Multidrug Resistance-Associated Proteins; Nephrolithiasis; Oxalates; Phosphatidylserines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; RNA; Urothelium

Mechanisms for calcium-based stone formation are not clearly delineated. Porcine are the most anatomically and physiologically congruent mammal to humans. Our objectives were to develop a cost-effective and easily reproducible porcine model for the study of calcium-based nephrolithiasis.. Crossbred male pigs (n = 16) were assigned randomly to one of the following treatments: (1) control; (2) ethylene glycol (EG) + vitamin D (VD); (3) EG + ammonium chloride (AC); (4) EG + gentamicin (G); (5) EG + Lasix; (6) EG + VD + AC; (7) EG + VD + G. Treatments were administered for 28 days; blood and urine were collected on day 0, 14, and 28. At the endpoint of the study, renal tissue was collected for gross and microscopic analysis of crystal stone formation and inflammation.. Stone-forming parameters were observed in serum and urine. For control versus all other treatments, by day 28, serum BUN and creatinine were less (P < 0.01), urinary creatinine, citrate and pH were greater (P < 0.01), and urinary oxalate was less (P < 0.01). Histopathological analysis of H&E staining and stone analysis revealed formation of calcium oxalate stones and crystal formation within the renal cortex and medulla for all animals except control. Nephrotoxicity was observed in one animal from treatment EG + G.. The treatments explored in this experiment provided novel examples of cost-effective porcine models for the study of nephrolithiasis. EG + VD had the strongest indicators of nephrolithiasis without nephrotoxicity.

Topics: Ammonium Chloride; Animals; Blood Urea Nitrogen; Calcium Oxalate; Citric Acid; Creatinine; Disease Models, Animal; Ethylene Glycol; Furosemide; Gentamicins; Hydrogen-Ion Concentration; Kidney Cortex; Kidney Medulla; Male; Nephrolithiasis; Oxalates; Swine; Urine; Vitamin D

Increasing evidence shows the importance of the commensal microbe Oxalobacter formigenes in regulating host oxalate homeostasis, with effects against calcium oxalate kidney stone formation, and other oxalate-associated pathological conditions. However, limited understanding of O. formigenes in humans poses difficulties for designing targeted experiments to assess its definitive effects and sustainable interventions in clinical settings. We exploited the large-scale dataset from the American Gut Project (AGP) to study O. formigenes colonization in the human gastrointestinal (GI) tract and to explore O. formigenes-associated ecology and the underlying host-microbe relationships.. In >8000 AGP samples, we detected two dominant, co-colonizing O. formigenes operational taxonomic units (OTUs) in fecal specimens. Multivariate analysis suggested that O. formigenes abundance was associated with particular host demographic and clinical features, including age, sex, race, geographical location, BMI, and antibiotic history. Furthermore, we found that O. formigenes presence was an indicator of altered host gut microbiota structure, including higher community diversity, global network connectivity, and stronger resilience to simulated disturbances.. Through this study, we identified O. formigenes colonizing patterns in the human GI tract, potential underlying host-microbe relationships, and associated microbial community structures. These insights suggest hypotheses to be tested in future experiments. Additionally, we proposed a systematic framework to study any bacterial taxa of interest to computational biologists, using large-scale public data to yield novel biological insights.

Topics: Adult; Data Mining; Feces; Female; Gastrointestinal Microbiome; Homeostasis; Humans; Male; Nephrolithiasis; Oxalates; Oxalobacter formigenes; Phylogeny; Statistics as Topic; Systems Biology; United States

Despite guidelines, routine 24-hour urine testing is completed in <10% of high-risk, recurrent stone formers. Using surrogates for metabolic testing, such as key patient characteristics, could obviate the cost and burden of this test while providing information needed for proper stone prevention counseling.. We performed a retrospective study of 392 consecutive patients from 2007 to 2014 with ≥2 lifetime stone episodes, >70% calcium oxalate by mineral analysis, and ≥1 24-hour urine collection. We compared mean 24-hour urine values by age in decades. We used logistic regression and receiver operating characteristic (ROC) curve analysis to assess the predictive ability of age, gender, body mass index (BMI), and comorbidities to detect abnormal 24-hour urine parameters.. The mean age of the cohort was 51 ± 16 years. Older age was associated with greater urinary oxalate (p-trend <0.001), lower urinary uric acid (UA) (p-trend = 0.007), and lower urinary pH (p-trend <0.001). A nonlinear association was noted between age and urinary calcium or citrate (calcium peaked at 40-49 years, p = 0.03; citrate nadired at 18-29 years, p = 0.001). ROC analysis of age, gender, and BMI to predict 24-hour urine abnormalities performed the best for hyperuricosuria (area under the curve [AUC] 0.816), hyperoxaluria (AUC 0.737), and hypocitraturia (AUC 0.740). Including diabetes mellitus or hypertension did not improve AUC significantly.. In our recurrent calcium oxalate cohort, age significantly impacted urinary calcium, oxalate, citrate, and pH. Along with gender and BMI, age can be used to predict key 24-hour urine stone risk results. These data lay the foundation for a risk prediction tool, which could be a surrogate for 24-hour urine results in recurrent stone formers, who are unwilling or unable to complete metabolic testing. Further validation of these findings is needed in other stone populations.

Topics: Adolescent; Adult; Age Factors; Aged; Body Mass Index; Calcium; Calcium Oxalate; Calcium Phosphates; Citrates; Citric Acid; Comorbidity; Diabetes Mellitus; Female; Humans; Hypercalciuria; Hyperoxaluria; Hypertension; Kidney Calculi; Male; Middle Aged; Nephrolithiasis; Obesity; Oxalates; Recurrence; Regression Analysis; Retrospective Studies; Sex Factors; Uric Acid; Urinalysis; Young Adult

We investigated the possible involvement of multidrug resistance protein 1 P-glycoprotein (MDR1 P-gp) in the oxalate-induced redistribution of phosphatidylserine in renal epithelial cell membranes.. Real-time PCR and western blotting were used to examine MDR1 expression in Madin-Darby canine kidney cells at the mRNA and protein levels, respectively, whereas surface-expressed phosphatidylserine was detected by the annexin V-binding assay.. Oxalate treatment resulted in increased synthesis of MDR1, which resulted in phosphatidylserine (PS) externalization in the renal epithelial cell membrane. Treatment with the MDR1 inhibitor PSC833 significantly attenuated phosphatidylserine externalization. Transfection of the human MDR1 gene into renal epithelial cells significantly increased PS externalization.. To our knowledge, this study is the first to show that oxalate increases the synthesis of MDR1 P-gp, which plays a key role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blotting, Western; Cell Membrane; Cells, Cultured; Cyclosporins; Dogs; Drug Resistance, Multiple; Flow Cytometry; Gene Expression Regulation; Humans; Nephrolithiasis; Oxalates; Phosphatidylserines; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Urothelium

Urinary oxalate excretion is a risk factor for nephrolithiasis and is a result of endogenous metabolism and gastrointestinal processes. Gastrointestinal absorption of oxalate has been well demonstrated but to our knowledge evidence for secretion of oxalate is absent in humans. The objective of this study was to measure the amount and conformation of oxalate in the stomach and small intestine of adult subjects undergoing gastrointestinal endoscopy.. Eleven adults participated in this study. Gastrointestinal fluid was collected from the stomach and small intestine during endoscopy. A determination of the soluble and insoluble components of oxalate was made by centrifugation of the sample and subsequent acidification of the resultant pellet and supernatant. Samples were processed and the amount of oxalate was measured by ion chromatography, the limit of which is 1.6 μM.. The majority of small intestinal samples contained some degree of oxalate. This is in contrast to the stomach where minimal oxalate was detected. There was a wide range of oxalate concentrations and a greater degree of insoluble oxalate in small intestinal samples.. Our results suggest that some degree of oxalate secretion in the small intestine may occur in the fasted state while this is less likely in the stomach. Further studies are warranted to provide definitive evidence of gastrointestinal secretion of oxalate.

Topics: Adult; Aged; Chromatography, Ion Exchange; Endoscopy, Gastrointestinal; Fasting; Female; Gastric Mucosa; Humans; Intestinal Absorption; Intestine, Small; Male; Middle Aged; Nephrolithiasis; Oxalates; Stomach

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Topics: Animals; Antiporters; Caco-2 Cells; Cell Line; Cell Line, Tumor; Cell Membrane; Chlorides; Glycosylation; Homeostasis; Humans; Ion Transport; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Nephrolithiasis; Opossums; Oxalates; Protein Transport; Sulfate Transporters

A number of medicinal plants are used for their diuretic, urolithiatic and anti-inflammatory effects on urinary system problems in Turkey and the most common traditional remedy for kidney stones is the tea of immortal flowers. The aim of this study is to evaluate the preventive effect of infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG) and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney stones.. Sodium oxalate (Ox-70mg/kg intraperitoneally) was used to induce kidney stones on Wistar albino rats. At the same time, two different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and 156mg/kg) were dissolved in the drinking water and administered to animals for 5 days. Potassium citrate was used as positive control in the experiments. During the experiment, water intake, urine volume and body weights of the animals were recorded. At the end of the experiments, liver, kidney and body weights of the animals were determined; biochemical analysis were conducted on urine, blood and plasma samples. Histopathological changes in kidney tissues were examined and statistical analysis were evaluated.. HS extract showed the highest preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a number of kidney stones were maximum in sodium oxalate group (stone formation score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels and increased citrate levels significantly. In addition, Helichrysum extracts regulated the negative changes in biochemical and hematological parameters occurred after Ox injection.. We conclude that Helichrysum extracts could reduce the formation and growth of kidney stones in Ox-induced urolithiasis and can be beneficial for patients with recurrent stones. In addition, this is the first study on the preventive effect of immortal flowers.

Topics: Animals; Citrates; Flowers; Helichrysum; Kidney; Male; Nephrolithiasis; Oxalates; Phytotherapy; Plant Extracts; Rats, Wistar; Uric Acid

Polymorphism of the gene for matrix GLA protein (MGP), a calcification inhibitor, is associated with nephrolithiasis. However, experimental investigations of MGP role in stone pathogenesis are limited. We determined the effect of renal epithelial exposure to oxalate (Ox), calcium oxalate (CaOx) monohydrate (COM) or hydroxyapatite (HA) crystal on the expression of MGP.. MDCK cells in culture were exposed to 0.3, 0.5 or 1 mM Ox and 33, 66 or 133-150 μg/cm(2) of COM/HA for 3-72 h. MGP expression and production were determined by Western blotting and densitometric analysis. Enzyme-linked immunosorbent assay was performed to determine MGP release into the medium. Hyperoxaluria was induced in male Sprague-Dawley rats by feeding hydroxyl-L-proline. Immunohistochemistry was performed to detect renal MGP expression.. Exposure to Ox and crystals led to time- and concentration-dependent increase in expression of MGP in MDCK cells. Cellular response was quicker to crystal exposure than to the Ox, expression being significantly higher after 3-h exposure to COM or HA crystals and more than 6 h of exposure to Ox. MGP expression was increased in kidneys of hyperoxaluric rats particularly in renal peritubular vessels.. We demonstrate increased expression of MGP in renal tubular epithelial cells exposed to Ox or CaOx crystals as well as the HA crystals. The most significant finding of this study is the increased staining seen in renal peritubular vessels of the hyperoxaluric rats, indicating involvement of renal endothelial cells in the synthesis of MGP.

Topics: Animals; Calcium Oxalate; Calcium-Binding Proteins; Cells, Cultured; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Durapatite; Epithelial Cells; Extracellular Matrix Proteins; Hydroxyproline; Hyperoxaluria; Kidney; Madin Darby Canine Kidney Cells; Male; Matrix Gla Protein; Nephrolithiasis; Oxalates; Rats; Rats, Sprague-Dawley; Time Factors

Low dietary K levels have been associated with increasing renal Ca excretion in humans, indicating a higher risk of calcium oxalate (CaOx) urolith formation. Therefore, the present study aimed to investigate whether dietary K also affects the urine composition of cats. A total of eight adult cats were fed diets containing 0·31 % native K and 0·50, 0·75 and 1·00 % K from KCl or KHCO₃ and were evaluated for the effects of dietary K. High dietary K levels were found to elevate urinary K concentrations (P<0·001). Renal Ca excretion was higher in cats fed the KCl diets than in those fed the KHCO₃ diets (P=0·026), while urinary oxalate concentrations were generally lower in cats fed the KCl diets and only dependent on dietary K levels in cats fed the KHCO₃ diets (P<0·05). Fasting urine pH increased with higher dietary K levels (P=0·022), reaching values of 6·38 (1·00 % KCl) and 7·65 (1·00 % KHCO₃). K retention was markedly negative after feeding the cats with the basal diet (-197 mg/d) and the 0·50 % KCl diet (-131 mg/d), while the cats tended to maintain their balance on being fed the highest-KCl diet (-23·3 mg/d). In contrast, K from KHCO₃ was more efficiently retained (P=0·018), with K retention being between -82·5 and 52·5 mg/d. In conclusion, the dietary inclusion of KHCO₃ instead of KCl as K source could be beneficial for the prevention of CaOx urolith formation in cats, since there is an association between a lower renal Ca excretion and a generally higher urine pH. The utilisation of K is distinctly influenced by the K salt, which may be especially practically relevant when using diets with low K levels.

Topics: Acid-Base Imbalance; Animals; Bicarbonates; Calcium; Calcium Oxalate; Cats; Diet; Feces; Female; Hydrogen-Ion Concentration; Kidney Tubules; Male; Nephrolithiasis; Oxalates; Potassium; Potassium Chloride; Potassium Compounds; Potassium Deficiency

Distinguishing calcium oxalate from uric acid stones is critical to identify those patients who may benefit from dissolution therapy and can also help direct preventive measures for stone growth. We aim to study whether 24-hour urine analysis may predict the urinary stone composition.. We retrospectively identified patients with calcium oxalate and uric acid stone compositions who also had a 24-hour urine collection within 3 months of stone analysis. Patients with calcium phosphate, cystine, and other stone compositions were excluded. Subjects were divided based on their stone type (calcium oxalate vs uric acid stones) and were compared according to demographic data and 24-hour urine analysis. Logistic regression analysis was performed to assess the association between stone composition and covariates. A nomogram was then constructed to predict uric acid stones over calcium oxalate stones.. Of the 1163 patients identified, 1054 (90.6%) had calcium oxalate stones and 109 (9.4%) had uric acid stones. On logistic regression, body mass index (BMI) (odds ratio [OR] 1.351, 95% confidence interval [CI] 1.133-1.609; P<0.001), urinary sodium (OR 1.021, 95% CI 1.004-1.037; P=0.013), calcium (OR 0.987, 95% CI 0.979-0.996; P=0.003), oxalate (OR 0.890, 95% CI 0.804-0.985; P=0.024), and uric acid (OR 0.989, 95% CI 0.982-0.997; P=0.005) were significant predictors for urinary stone composition. The nomogram with the highest concordance index (c-index=0.855) was obtained using age, BMI, urinary sodium, calcium, oxalate, and uric acid as variables.. Distinguishing uric acid from calcium oxalate stones can be performed with relative accuracy using parameters from the 24-hour urine stone risk profile and the patient's BMI and age.

Topics: Body Mass Index; Calcium; Calcium Oxalate; Diagnosis, Differential; Female; Humans; Kidney Calculi; Male; Middle Aged; Nephrolithiasis; Nomograms; Oxalates; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Sodium; Time Factors; Uric Acid

We used computer modeling to investigate the influence of physicochemical stone risk factors on urinary supersaturation (SS) of calcium oxalate (CaOx) in patients with severe hyperoxaluria, relative hypocalciuria, hypocitraturia, and CaOx nephrolithiasis after extensive small bowel resection, usually performed for Crohn's disease. We also simulated different treatment strategies, including oral calcium supplements and citrate, in such patients.. A baseline urine model was derived by consolidating data acquired by ourselves with those from another patient cohort. Calcium and oxalate excretions in this model were altered to obtain an extreme case. For comparison, additional models were based on published urine data from normal subjects (N) and idiopathic CaOx stone formers (SF). The Joint Expert Speciation System was used to simulate different urine situations based on reported compositional values.. [Ca(2+)][Ox(2-)] ionic concentration products and SS(CaOx) are substantially higher in enteric hyperoxaluric patients than in N and SF, despite their relatively lower calcium excretions. Molar Ca:Ox ratios are substantially lower in enteric hyperoxalurics than in N and SF. Oral calcium supplements can reduce SS(CaOx), but monitoring is required to avoid exceeding a safe dosing threshold. A simple calculation can alert the clinician that this threshold is being approached or even exceeded. Increasing urinary pH and citrate decreases SS(CaOx) but not to the same extent as decreasing Ox excretion.. Calcium supplements can help reduce stone risk in patients with severe enteric hyperoxaluria, but initial efforts should be directed toward reducing urinary oxalate by reducing dietary oxalate. Citrate therapy that increases both urine pH and urinary citrate provides an additional therapeutic benefit.

Topics: Calcium Oxalate; Calcium, Dietary; Chelating Agents; Citric Acid; Clinical Protocols; Computer Simulation; Diagnosis, Computer-Assisted; Diet; Female; Humans; Hyperoxaluria; Intestine, Small; Male; Middle Aged; Nephrolithiasis; Oxalates; Postoperative Complications; Risk Factors; Urinary Calculi

To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis.. The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system.. The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments.. Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

Topics: Caffeine; Crystallization; Humans; Microscopy, Electron, Scanning; Nephrolithiasis; Oxalates; Theobromine; Uric Acid

The composition of urine is influenced by diet and changes in dietary factors have been proposed to modify the risk of recurrent nephrolithiasis. Nutrients that have been implicated include calcium, oxalate, sodium, animal protein, magnesium and potassium. There is significant evidence showing that a high calcium diet is associated with a reduction of lithogenic risk. One of the possible mechanisms to explain this apparent paradox is that the higher intake of calcium in the intestine binds with dietary oxalate, reducing its absorption and urinary excretion. Oxalate from the diet seems to provide only a small contribution to excretion and dietary restriction is appropriate only in those with hyperoxaluria and hyperabsorption. Observational studies have shown a positive and independent association between sodium intake and the formation of new kidney stones. Consumption of animal protein creates an acid load that increases urinary excretion of calcium and uric acid and reduced citrate, all factors that could participate in the genesis of stones. Potassium-rich foods increase urinary citrate because of its alkali content. In prospective observational studies, diets rich in magnesium were associated with a lower risk of kidney stone formation in men. In conclusion, diet is a key element in the management of the patient with kidney stones but always subordinated to present metabolic risk factors.

Topics: Calcium, Dietary; Dietary Proteins; Humans; Hyperoxaluria; Nephrolithiasis; Oxalates; Sodium, Dietary

Chinese herbs Desmodium styracifolium (Ds) and Pyrrosiae petiolosa (Pp) have been widely used to treat urolithiasis with few side effects in traditional Chinese medicine (TCM). In vitro crystallization study has confirmed their prophylaxis of Calcium oxalate (CaO( x )) stones formation. However, little is known on their possible mechanisms in vivo. In the present study, we proposed to systematically evaluate their antilithic effects and clarify the underlying mechanism of Ds and Pp using a rat nephrolithiasis model and administering the aqueous extracts. Adult male Wistar rats were fed with 5% ammonium oxalate (AmO( x )) forage to induce nephrolithiasis. After 1 week, the rats were randomly divided into eight groups, and given low, medium, and high dose of each herb treatments (275, 550 and 1,100 mg/kg for Ds and 150, 300 and 600 mg/kg for Pp) by gavage for 3 weeks. In contrast to urolithic rats, urinary oxalate significantly reduced, and urinary calcium increased in medium and high dose Ds groups. Few depositions were observed in kidney with slight dilation of tubules and inflammatory infiltration. Osteopontin (OPN), nitric oxide (NO), and malondialdehyde (MDA) levels significantly decreased, but Superoxide dismutase (SOD) activities were enhanced in kidneys. In high dose Pp group, crystals were found in the dilation of tubules with slight inflammatory infiltration. Partial serum and urinary variables returned to the normal range. In conclusion, medium and high dose Ds has beneficial effect in preventing CaO( x ) stone formation by rising urinary Citrate excretion, decreasing urinary calcium, diuresis, and antioxidative effects. Although high dose Pp has relatively weak prophylaxis, it indicates significant anti-inflammatory and antioxidant effects.

Topics: Animals; Calcium Oxalate; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Kidney; Male; Malondialdehyde; Models, Animal; Nephrolithiasis; Nitric Oxide; Osteopontin; Oxalates; Rats; Rats, Wistar; Superoxide Dismutase

Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. It has been shown that celiac disease, a common malabsorption disorder, is associated with an increased risk of calcium oxalate kidney stones in adults. Since no published data are available in the pediatric population, we analyzed urinary excretion of electrolytes in children with celiac disease to assess the risk of nephrolithiasis.. The study population consisted of 115 children 1 to 16 years old (mean 5 years) with positive serological tests for celiac disease (anti-endomysium and anti-tissue transglutaminase antibodies) referred to us for jejunal biopsy to confirm the diagnosis. Assessment was requested because patients presented with poor growth, anemia, gastrointestinal disorders or a family history of celiac disease. After obtaining informed consent we performed urine tests to measure urinary variables and blood tests to exclude metabolic disorders and evaluate renal function.. All patients had a biopsy confirmed diagnosis of celiac disease. Oxaluria was normal in all children studied. However, levels of urinary calcium were decreased in patients with celiac disease and were inversely associated with disease severity (p = 0.0004).. In contrast to adults, increased urinary excretion of oxalate was not detectable in children presenting with celiac disease. Therefore, the risk of nephrolithiasis appears not to be increased compared to healthy children. The observed hypocalciuria probably further decreases the tendency to form kidney stones.

Topics: Adolescent; Age Factors; Calcium; Celiac Disease; Child; Child, Preschool; Creatinine; Female; Humans; Infant; Magnesium; Male; Nephrolithiasis; Oxalates; Phosphorus; Reference Values; Risk Factors

Metabolic syndrome is a risk factor for nephrolithiasis. This study was performed to evaluate the clinical and biochemical profile of calcium-oxalate nephrolithiasis in stone formers with metabolic syndrome.. A total of 526 recurrent stone formers, 184 of them with metabolic syndrome, and 214 controls were examined on a free diet and after a sodium-restricted diet (sodium intake < 100 mmol/24 h).. On free diet, stone formers with metabolic syndrome showed higher sodium excretion [mean (95% confidence interval), 196 (176-218) vs 160 (150-168) mmol/24 h; P < 0.01] and lower citrate excretion [2.23 (1.99-2.58) vs 2.84 (2.51-3.17) mmol/24 h; P < 0.01] compared to controls, whereas stone formers without metabolic syndrome showed higher calcium and oxalate excretion [5.43 (5.01-5.82) vs 3.58 (2.84-4.19) and 0.34 (0.32-0.36) vs 0.26 (0.20-0.31)m mmol/24 h for calcium and oxalate, respectively; P < 0.01] and lower citrate excretion [2.18 (1.98-2.38) vs 2.84 (2.51-3.17) mmol/24 h; P < 0.01] compared to controls. The ion activity product of urinary calcium-oxalate salts was similar between stone formers with and without metabolic syndrome [1.41 (1.31-1.59) vs 1.40 (1.35-1.45); P > 0.05]. After the test diet, this index was lower in diet-compliant stone formers with metabolic syndrome compared to diet-compliant stone formers without metabolic syndrome [1.15 (1.10-1.21) vs 1.39 (1.31-1.45); P < 0.01].. The biochemical profiles and responses to the sodium-restricted diet were significantly different between stone formers with metabolic syndrome and those without. Dietary habits play a central role in the pathogenesis of nephrolithiasis in stone formers with metabolic syndrome.

Topics: Adult; Calcium; Calcium Oxalate; Diet, Sodium-Restricted; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Function Tests; Male; Metabolic Syndrome; Middle Aged; Nephrolithiasis; Oxalates; Prognosis; Recurrence; Risk Factors

Hyperoxaluria is a major problem causing nephrolithiasis. Little is known about the regulation of oxalate transport from the liver, the main organ for oxalate synthesis, into the circulation. Since the sulfate anion transporter-1(sat-1) is present in the sinusoidal membrane of hepatocytes and translocates oxalate, its impact on increased oxalate synthesis was studied.. Sat-1 expressing oocytes were used for cis-inhibition, trans-stimulation, and efflux experiments with labelled sulfate and oxalate to demonstrate the interactions of oxalate, glyoxylate, and glycolate with sat-1. HepG2 cells were incubated with oxalate and its precursors (glycine, hydroxyproline, glyoxylate, and glycolate). Changes in endogenous sat-1 mRNA-expression were examined using real-time PCR. After incubation of HepG2 cells in glyoxylate, sat-1 protein-expression was analysed by Western blotting, and sulfate uptake into HepG2 cells was measured. RT-PCR was used to screen for mRNA of other transporters.. While oxalate and glyoxylate inhibited sulfate uptake, glycolate did not. Sulfate and oxalate uptake were trans-stimulated by glyoxylate but not by glycolate. Glyoxylate enhanced sulfate efflux. Glyoxylate was the only oxalate precursor stimulating sat-1 mRNA-expression. After incubation of HepG2 cells in glyoxylate, both sat-1 protein-expression and sulfate uptake into the cells increased. mRNA-expression of other transporters in HepG2 cells was not affected by glyoxylate treatment.. The oxalate precursor glyoxylate was identified as a substrate of sat-1. Upregulated expression of sat-1 mRNA and of a functional sat-1 protein indicates that glyoxylate may be responsible for the elevated oxalate release from hepatocytes observed in hyperoxaluria.

Topics: Animals; Anion Transport Proteins; Base Sequence; DNA Primers; Female; Glycolates; Glyoxylates; Hep G2 Cells; Hepatocytes; Humans; Hyperoxaluria; In Vitro Techniques; Models, Biological; Nephrolithiasis; Oocytes; Oxalates; Recombinant Proteins; RNA, Messenger; Sulfate Transporters; Sulfates; Up-Regulation; Xenopus laevis

Hyperoxaluria and increased calcium oxalate stone formation occur after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity. The etiology of this hyperoxaluria is unknown. We hypothesized that after bariatric surgery, intestinal hyperabsorption of oxalate contributes to increases in plasma oxalate and urinary calcium oxalate supersaturation.. We prospectively examined oxalate metabolism in 11 morbidly obese subjects before and 6 and 12 months after RYGB (n = 9) and biliopancreatic diversion-duodenal switch (BPD-DS) (n = 2). We measured 24-hour urinary supersaturations for calcium oxalate, apatite, brushite, uric acid, and sodium urate; fasting plasma oxalate; 72-hour fecal fat; and increases in urine oxalate following an oral oxalate load.. Six and 12 months after RYGB, plasma oxalate and urine calcium oxalate supersaturation increased significantly compared with similar measurements obtained before surgery (all P ≤ .02). Fecal fat excretion at 6 and 12 months was increased (P = .026 and .055, 0 vs 6 and 12 months). An increase in urine oxalate excretion after an oral dose of oxalate was observed at 6 and 12 months (all P ≤ .02). Therefore, after bariatric surgery, increases in fecal fat excretion, urinary oxalate excretion after an oral oxalate load, plasma oxalate, and urinary calcium oxalate supersaturation values were observed.. Enteric hyperoxaluria is often present in patients after the operations of RYGB and BPD-DS that utilize an element of intestinal malabsorption as a mechanism for weight loss.

Topics: Adult; Aged; Calcium Oxalate; Dietary Fats; Female; Follow-Up Studies; Gastric Bypass; Humans; Hyperoxaluria; Intestinal Absorption; Malabsorption Syndromes; Middle Aged; Nephrolithiasis; Obesity, Morbid; Oxalates; Postoperative Complications; Prospective Studies; Risk Factors; Weight Loss

Recent epidemiological studies revealed an association of obesity, diabetes mellitus, hypertension and metabolic syndrome (MetS) with kidney stone disease. We examined how these disorders cause kidney stones. A clinical study on 467 patients with nephrolithiasis at our institution revealed that clustering of MetS traits increased the risk of uric acid stone formation by decreasing urinary pH. A subsequent study analyzing detailed data from 30,448 patients enrolled in the 6th Nationwide Survey on Urolithiasis in Japan showed that clustering of MetS traits were associated with an increased severity of the kidney stone disease and elevated urinary excretion of calcium, uric acid and oxalate. Finally, the OLETF rats, an animal model of MetS, showed lower urinary pH, decreased citrate excretion, and increased uric acid and calcium excretion. In addition, the administration of pioglitazone, an agent that improves insulin resistance, significantly increased the urinary pH. These results indicate that MetS causes changes in urinary constituents, leading to an increased risk of both uric acid and calcium oxalate stone formation. We suggest that kidney stone disease should be considered as a component of MetS and that the improvement in insulin resistance by means of diet and lifestyle changes and medical therapy might help to prevent this disorder.

Topics: Animals; Calcium; Humans; Hydrogen-Ion Concentration; Insulin Resistance; Metabolic Syndrome; Nephrolithiasis; Oxalates; Rats; Uric Acid; Urine

Several animal species are used to study calcium oxalate urolithiasis; however, an ideal model has yet to be identified. We used Drosophila as a model organism and fed the flies lithogenic agents such as ethylene glycol, hydroxyl-L-proline, and sodium oxalate. At different times, the Malpighian tubules, the kidney equivalent of insects, were dissected and a polarized light microscope used to highlight the birefringent crystals. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed that the crystal composition was predominately calcium oxalate. Furthermore, administration of potassium citrate successfully reduced the quantity of and modulated the integrity of the ethylene glycol-induced crystals. Thus, the Drosophila model of bio-mineralization produces crystals in the urinary system through many lithogenic agents, permits observation of crystal formation, and is amenable to genetic manipulation. This model may mimic the etiology and clinical manifestations of calcium oxalate stone formation and aid in identification of the genetic basis of this disease.

Topics: Aging; Animals; Calcium Oxalate; Crystallization; Disease Models, Animal; Drosophila melanogaster; Ethylene Glycol; Female; Hydroxyproline; Longevity; Male; Malpighian Tubules; Microscopy, Electron, Scanning; Microscopy, Polarization; Nephrolithiasis; Oxalates; Potassium Citrate; Spectrometry, X-Ray Emission; Triazines; Urolithiasis

A microchip-CE device was fabricated for bed-side monitoring of nephrolithiasis biomarkers in urine by incorporating on-chip continuous passive mixing and standard addition to reduce sample matrix interference, increase sample throughput and eliminate accessories for active mixing. Under optimized conditions with buffer containing 20 mM borate and 0.5 mM CTAB at pH 10.3, sample and standards injected electrokinetically at -350 V for 10 s for online mixing in a Y-merging flow microchannel prior to CE separation and UV detection at 210 nm, both inhibitors (citrate, CA) and promoters (oxalate, OA and uric acid, UA) for nephrolithiasis can be separated and determined in human urine in a single run completed within 10 min after a simple 50-fold sample dilution and filtering. Satisfactory working ranges from 0.13-40, 0.25-40 and 0.025-40 mM, LOD 2.6, 6.1 and 0.7 μM, repeatability (%RSD, n=5) for migration time 1.40, 1.43, 0.47 and peak area 4.46, 6.10, 1.98, respectively, for CA, OA and UA are obtained for urine samples. The use of on-chip standard addition is shown to improve repeatability of the migration time, assist the identification of nephrolithiasis markers from difficult samples with noisy baseline and enlarge the working range for nephrolithiasis marker determination. The device developed can be used for both routine and emergency monitoring to deliver results on demand for bedside monitoring and public health protection. It provides an early detection of nephrolithiasis to enable timely treatments, ease anxiety of parents for neonates consuming suspected contaminated food, and quick results for patients in a critical condition.

Topics: Biomarkers; Citric Acid; Electrophoresis, Microchip; Equipment Design; Humans; Limit of Detection; Nephrolithiasis; Oxalates; Reproducibility of Results; Time Factors; Uric Acid

We evaluated the metabolic and the nutritional aspects of 134 urolithiasic children, in order to outline the risk factors that contribute to idiopathic stone formation in children.. In this prospective study 134 children (56 females, 78 males) with renal calculi were evaluated. The age of the patients ranged 6 months to 16 years. A dietary survey was performed on every child. All patients were investigated with respect to stone localization, serum and urine risk factors. Statistical analysis of data was carried out using software SPSS 11.0 for Windows. Statistical significance was determined using chi-square test.. Hypercalciuria was the commonest risk factor detected in this group (28.3%). A decrease of water intake was noted in all age group specially in the rural area (549.6 vs 1150.6 ml/day), and an increase in animal protein intake in 17 cases (mean 1.9 g/kg). In addition, increased intake of starchy foods and food with high oxalate content (sorgum) was observed in our 10-16 years group (51%). Calcium oxalate monohydrate represents the principal component of idiopathic stone (58.2%), which is more frequent in children (68%) than infants (51.7%) (P < 0.02).. The high frequency of idiopathic urolithiasis highlights the influence of dietary habit in stone formers in our country. The increase in calcium oxalate stones in school-age children confirms the change in the etiology of urolithiasis according to age.

Topics: Adolescent; Child; Child, Preschool; Diet; Diet Surveys; Drinking; Feeding Behavior; Female; Humans; Hypercalciuria; Infant; Male; Meat; Nephrolithiasis; Oxalates; Prevalence; Prospective Studies; Risk Factors; Tunisia

Renal protection and antiurolithiasic effects of two extracts of Paronychia argentea (PA), a traditional Algerian plant commonly known as Algerian tea, were evaluated. This study was carried out to determine whether the aqueous extract (APA) or the butanolic extract (BPA) of aerial parts could prevent or reduce calculi aggregation in experimental calcium oxalate (Ox) nephrolithiasis in Wistar rats.. The two extracts (APA and BPA) were administrated orally and daily, during 28 days to nephrolithiasic treated rats at the dose of 250, 500 mg/kg b.w. and 10, 20mg/kg b.w. respectively. Body weight, renal index, liver index, serum level of creatinine, uric acid, urea, K(+), Ca(2+), Mg(2+), Na(+) and transaminase (alanine aminotransferase, ALT; aspartate aminotransferase, AST), phosphatase alkaline activity (PAL) were evaluated following the 28 days treatment in rats. In addition histopathological changes in kidney and liver were stained in hematoxylin eosin (HE).. The effect of the extracts could be advantageous in preventing urinary stone retention by reducing renal necrosis and thus inhibit crystal retention. In contradiction with APA, the two doses of BPA attenuated elevation in the serum creatinine (p<0.01) and blood urea levels (p<0.01) (nephroprotective effect). However, the increase in ALT (27%) and PAL (31-51%) serum levels and in the relative liver weights (p<0.01) in the groups treated with doses of APA may indicate that this extract has not a hepatoprotective effect against oxalate toxicity.. The presented data indicate that administration of the butanolic extract of aerial parts to rats with NaOx induced lithiasis, and reduced and prevented the growth of urinary stones in experimental calcium oxalate nephrolithiasis in Wistar rats.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Calcium Oxalate; Caryophyllaceae; Creatinine; Disease Models, Animal; Kidney; Kidney Calculi; Liver; Male; Necrosis; Nephrolithiasis; Organ Size; Oxalates; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats; Rats, Wistar; Urea

It had been suggested that lactic acid bacteria (LAB) may degrade oxalate in the intestinal lumen, reducing urinary oxalate excretion. We aimed to evaluate the effect of a LAB mixture containing Lactobacillus casei (LC) and Bifidobacterium breve (BB) (LC + BB) upon urinary oxalate reduction in stone-forming (SF) patients without hyperoxaluria under conditions of an oxalate-rich diet. After an oxalate restriction period (7 days washout), 14 SF patients consumed an oxalate-rich diet during 4 weeks (200 mg/day) and a lyophilized LC + BB preparation was given t.i.d. after meals during the last 2 weeks. Twenty-four-hour urine samples were collected for determination of oxalate, calcium, magnesium, citrate, sodium, potassium and creatinine at baseline, after 2 weeks (DIET) and 4 weeks (DIET + LC + BB). The mean urinary oxalate excretion was significantly higher after DIET versus baseline (27 +/- 8 vs. 35 +/- 11 mg/24 h), but the mean decrease was not significant between DIET + LC + BB and DIET periods (35 +/- 11 vs. 33 +/- 10 mg/24 h). Seven out of 14 patients presented a reduction in oxaluria after LC + BB versus DIET, being the reduction higher than 25% in 4, and up to 50% in 2 of them. The latter two patients were those who had presented the greatest increase in oxaluria in response to dietary oxalate. In conclusion, this mixture of L. casei and B. breve was shown to possess a variable lowering effect upon urinary oxalate excretion that may be dependent on dietary oxalate intake.

Topics: Adult; Bifidobacterium; Diet; Female; Food Analysis; Humans; Lacticaseibacillus casei; Male; Middle Aged; Nephrolithiasis; Oxalates; Probiotics

The mouse is refractory to lithogenic agents active in rats and humans, and so has been traditionally considered a poor experimental model for nephrolithiasis. However, recent studies have identified slc26a6 as an oxalate nephrolithiasis gene in the mouse. Here we extend our earlier demonstration of different anion selectivities of the orthologous mouse and human SLC26A6 polypeptides to investigate the correlation between species-specific differences in SLC26A6 oxalate/anion exchange properties as expressed in Xenopus oocytes and in reported nephrolithiasis susceptibility. We find that human SLC26A6 mediates minimal rates of Cl(-) exchange for Cl(-), sulphate or formate, but rates of oxalate/Cl(-) exchange roughly equivalent to those of mouse slc2a6. Both transporters exhibit highly cooperative dependence of oxalate efflux rate on extracellular [Cl(-)], but whereas the K(1/2) for extracellular [Cl(-)] is only 8 mM for mouse slc26a6, that for human SLC26A6 is 62 mM. This latter value approximates the reported mean luminal [Cl(-)] of postprandial human jejunal chyme, and reflects contributions from both transmembrane and C-terminal cytoplasmic domains of human SLC26A6. Human SLC26A6 variant V185M exhibits altered [Cl(-)] dependence and reduced rates of oxalate/Cl(-) exchange. Whereas mouse slc26a6 mediates bidirectional electrogenic oxalate/Cl(-) exchange, human SLC26A6-mediated oxalate transport appears to be electroneutral. We hypothesize that the low extracellular Cl(-) affinity and apparent electroneutrality of oxalate efflux characterizing human SLC26A6 may partially explain the high human susceptibility to nephrolithiasis relative to that of mouse. SLC26A6 sequence variant(s) are candidate risk modifiers for nephrolithiasis.

Topics: Animals; Antiporters; Chlorides; Female; Genetic Predisposition to Disease; Humans; Hydrogen-Ion Concentration; Hyperoxaluria; Membrane Potentials; Membrane Transport Proteins; Mice; Nephrolithiasis; Oocytes; Oxalates; Patch-Clamp Techniques; Species Specificity; Sulfate Transporters; Transfection; Xenopus laevis

Topics: Animals; Antiporters; Chlorides; Genetic Predisposition to Disease; Humans; Membrane Transport Proteins; Mice; Nephrolithiasis; Oxalates; Sulfate Transporters

Most kidney stones consist of calcium oxalate, and higher urinary oxalate increases the risk for calcium oxalate nephrolithiasis. However, the relation between dietary oxalate and stone risk is unclear. This study prospectively examined the relation between oxalate intake and incident nephrolithiasis in the Health Professionals Follow-up Study (n = 45,985 men), the Nurses' Health Study I (n = 92,872 older women), and the Nurses' Health Study II (n = 101,824 younger women). Food frequency questionnaires were used to assess oxalate intake every 4 yr. Cox proportional hazards regression was used to adjust for age, body mass index, thiazide use, and dietary factors. A total of 4605 incident kidney stones were documented over a combined 44 yr of follow-up. Mean oxalate intakes were 214 mg/d in men, 185 mg/d in older women, and 183 mg/d in younger women and were similar in stone formers and non-stone formers. Spinach accounted for >40% of oxalate intake. For participants in the highest compared with lowest quintile of dietary oxalate, the relative risks for stones were 1.22 (95% confidence interval [CI] 1.03 to 1.45; P = 0.01 for trend) for men and 1.21 (95% CI 1.01 to 1.44; P = 0.05 for trend) for older women. Risk was higher in men with lower dietary calcium (P = 0.08 for interaction). The relative risks for participants who ate eight or more servings of spinach per month compared with fewer than 1 serving per month were 1.30 (95% CI 1.08 to 1.58) for men and 1.34 (95% CI 1.10 to 1.64) for older women. Oxalate intake and spinach were not associated with risk in younger women. These data do not implicate dietary oxalate as a major risk factor for nephrolithiasis.

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nephrolithiasis; Oxalates; Prospective Studies; Risk Factors

Topics: Blood; Body Fluids; Humans; Hypercalcemia; Hyperparathyroidism; Kidney Calculi; Nephrolithiasis; Oxalates; Uric Acid; Urine

Topics: Citrates; Humans; Kidney Calculi; Lithiasis; Nephritis; Nephrolithiasis; Oxalates; Phosphates; Uric Acid; Urine

Topics: Calcium; Calcium, Dietary; Citrates; Kidney Calculi; Magnesium; Nephrolithiasis; Oxalates; Pharmacology; Phosphates; Phosphorus; Phosphorus, Dietary; Pyridoxine; Rats; Research; Sulfates; Sulfur; Urine; Vitamin B 6

Topics: Calcium; Calcium, Dietary; Carbohydrate Metabolism; Glycine; Humans; Lithiasis; Mexico; Minerals; Nephrolithiasis; Oxalates; Pathology; Proteins; Serine; Uric Acid; Urinary Calculi

Topics: Humans; Kidney Calculi; Lithiasis; Nephrolithiasis; Oxalates; Phosphates; Psychophysiologic Disorders; Psychosomatic Medicine; Psychotherapy; Research; Uric Acid

Topics: Acidosis; Alkalies; Humans; Hyperparathyroidism; Kidney Calculi; Lithiasis; Milk; Nephrolithiasis; Osteoporosis; Oxalates; Sarcoidosis; Urinary Tract Infections; Vitamin D

Topics: Calcium; Humans; Hypercalciuria; Lithiasis; Male; Nephrolithiasis; Oxalates; Urinary Calculi; Water-Electrolyte Balance

Topics: Acute Kidney Injury; Child; Humans; Hyperoxaluria; Infant; Kidney Calculi; Nephrolithiasis; Oxalates; Renal Insufficiency; Urinary Calculi

Topics: Ethylene Glycol; Glycols; Humans; Lipid Metabolism; Lipids; Lithiasis; Nephrolithiasis; Oxalates; Oxalic Acid; Urinary Calculi

Topics: Body Fluids; Calculi; Humans; Kidney; Kidney Calculi; Nephrolithiasis; Oxalates; Oxalic Acid

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

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