Urinary Oxalate Concentration Research Articles

Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4)

Nedosiran is an N-acetyl-D-galactosamine (GalNAc)–conjugated RNA interference agent targeting hepatic lactate dehydrogenase (encoded by the LDHA gene), the putative enzyme mediating the final step of oxalate production in all three genetic subtypes of primary hyperoxaluria (PH). This phase I study assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous nedosiran in patients with PH subtype 3 (PH3) and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. Single-dose nedosiran 3 mg/kg or placebo was administered in a randomized (2:1), double-blinded manner. Safety/tolerability, 24-h urinary oxalate (Uox) concentrations, and plasma nedosiran concentrations were assessed. The main PD endpoint was the proportion of participants achieving a > 30% decrease from baseline in 24-h Uox at two consecutive visits. Six participants enrolled in and completed the study (nedosiran, n = 4; placebo, n = 2). Nedosiran was well-tolerated and lacked safety concerns. Although the PD response was not met, 24-h Uox excretion declined 24.5% in the nedosiran group and increased 10.5% in the placebo group at Day 85. Three of four nedosiran recipients had a > 30% reduction in 24-h Uox excretion during at least one visit, and one attained near‐normal (i.e., ≥ 0.46 to < 0.60 mmol/24 h; ≥ 1.0 to < 1.3 × upper limit of the normal reference range) 24-h Uox excretion from Day 29 to Day 85. Nedosiran displayed predictable plasma PK. The acceptable safety and trend toward Uox-lowering after single-dose nedosiran treatment enables further clinical development of nedosiran in patients with PH3 who currently have no viable therapeutic options. A plain language summary is available in the supplementary information.

Enzyme-based color bar-style lateral flow strip for equipment-free and semi-quantitative determination of urinary oxalate

Urolithiasis is a highly prevalent disease with increasing incidence worldwide, which occurs mainly as calcium oxalate. Therefore, measuring urinary oxalate for the early screening of urolithiasis is of growing significance. However, current approaches for oxalate detection are generally based on specific equipment, thus limiting their point-of-care applications. In this study, a colorimetric lateral flow strip was developed based on enzyme catalysis, and a color bar strategy was utilized for equipment-free and semi-quantitative determination of urinary oxalate, which does not require any image acquisition or processing equipment. Rapid semi-quantitative detection of oxalate is achieved by directly counting the number of color bars that is positively correlated with oxalate concentration. Three colorimetric patterns were compared and optimized, among which the one with 3,3',5,5'-tetramethylbenzidine (TMB) scribes presented the best results with minimized drag impact, washing effects and limited inter-reagent reactions in the lateral flow. Under optimized conditions, the assay showed a detection limit less than 0.3 mM and a detection range of 0.3–0.7 mM that covers the urinary oxalate concentrations for urolithiasis screening. Finally, the strips were verified for real urine sample analysis, validating its potential for oxalate detection and urolithiasis screening in point-of-care applications.

Estimating 24-hour urinary excretion using spot urine measurements in kidney stone formers.

ABSTRACTBackgroundOne limitation of the use of 24-hour collection is impracticality. We analysed the performance of spot urine measurements to estimate 24-hour excretion in patients with kidney stones.MethodsA total of 74 adult patients from two centres performed a 24-hour urine collection. A sample of the last micturition was sent for spot urine analysis. Twenty patients were asked to collect two additional spot urine samples, one before dinner and the other after dinner. Urinary concentrations of creatinine, calcium, oxalate, uric acid, citrate and magnesium were measured in the 24-hour and each of the spot urine samples. Four approaches were used to estimate 24-hour urinary excretion, multiplying the ratio of the spot urinary analyte to creatinine concentration by (i) measured 24-hour urinary creatinine excretion (Prediction 1), (ii) estimated 24-hour urinary creatinine excretion (Prediction 2), (iii) assumed 1-g 24-hour urinary creatinine excretion (Prediction 3) or (iv) assumed 1.5-g 24-hour urinary creatinine excretion (Prediction 4). For each parameter we computed Lin's concordance correlation coefficients (CCCs), Bland–Altman plots and 95% limits of agreement.ResultsThe performance of estimates obtained with Prediction 1 and Prediction 2 was similar, except for citrate and uric acid, for which Prediction 2 performed worse. Both approaches performed moderately well: citrate CCC {0.82 [95% confidence interval (CI) 0.75–0.90]}, oxalate [0.66 (95% CI 0.55–0.78)], magnesium [0.66 (95% CI 0.54–0.77)], calcium [0.63 (95% CI 0.50–0.75)] and uric acid [0.52 (95% CI 0.36–0.68)]. The performance of Predictions 3 and 4 was worse.ConclusionsAlthough spot urine samples may hold promise for clinical and population-based research, at present they have limited utility in clinical practice. Measuring or estimating 24-hour creatinine, rather than assuming a given creatinine excretion, will be necessary in future studies of spot urine samples.

Synbiotic supplementation and oxalate homeostasis in rats: focus on microbiota oxalate-degrading activity

The present study aimed (i) to evaluate whether ceftriaxone treatment could affect not only intestinal oxalate-degrading bacteria number but also their total activity to degrade oxalate and influence oxalate homeostasis in rats, (ii) and to estimate the ability of commercially available inulin-contained synbiotic to restore fecal oxalate-degrading activity and ceftriaxone-induced disruption of oxalate homeostasis in rats. Twenty-eight female Wistar rats (200-300g) were randomly divided into four groups (n = 7). Group 1 was treated with vehicle sterile water (0.1ml, i.m., 14days); Group 2 received synbiotic (30mg/kg, per os, 14days); Group 3 was treated with ceftriaxone (300mg/kg, i.m., 7days); Group 4 was supplemented with ceftriaxone and synbiotic. Oxalate-degrading bacteria number and their total activity, urinary and plasma oxalate concentrations were measured on days 1 and 57 after the treatment withdrawal. The redoximetric titration with KMnO4 was adopted to evaluate the total oxalate-degrading activity in highly selective Oxalate Medium. Ceftriaxone treatment reduced total fecal oxalate-degrading activity independently on oxalate-degrading bacteria number and increased urinary and plasma oxalate concentrations. The synbiotic had higher oxalate-degrading activity vs probiotics and was able to restore fecal oxalate-degrading activity and significantly decrease urinary oxalate excretion in antibiotic-treated rats. Total fecal oxalate-degrading activity but not oxalate-degrading bacteria number should be thoroughly examined in the future to develop predictive diagnostics methods, targeted prevention and personalized treatment in kidney stone disease. Synbiotic supplementation had a beneficial effect on the total oxalate-degrading activity of gut microbiota, which resulted in decreased UOx excretion in rats.

MP07-12 REVISITING THE ROLE OF OXALOBACTER FORMIGENES IN STONE FORMATION: A DEEP DIVE INTO THE MICROBIOME AT MULTIPLE BODY SITES

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-12 REVISITING THE ROLE OF OXALOBACTER FORMIGENES IN STONE FORMATION: A DEEP DIVE INTO THE MICROBIOME AT MULTIPLE BODY SITES Kait Al, Benjamin Joris, John Denstedt, John Chmiel, Jennifer Bjazevic, Gregory Gloor, Hassan Razvi, and Jeremy Burton Kait AlKait Al More articles by this author , Benjamin JorisBenjamin Joris More articles by this author , John DenstedtJohn Denstedt More articles by this author , John ChmielJohn Chmiel More articles by this author , Jennifer BjazevicJennifer Bjazevic More articles by this author , Gregory GloorGregory Gloor More articles by this author , Hassan RazviHassan Razvi More articles by this author , and Jeremy BurtonJeremy Burton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is a longstanding belief that intestinal colonization by Oxalobacter formigenes can reduce the risk of oxalate-based stone disease through its capacity to degrade calcium oxalate. However, literature on the topic remains controversial, and mounting evidence instead suggests a polymicrobial effect from both the urinary and gut microbiome may play a greater role in the disease. The aim of the present study was to address this knowledge gap by comprehensively characterizing the microbial communities of interest in kidney stone formers and healthy controls. METHODS: In the largest study of its kind, the microbiota of fecal and urine samples from 83 stone formers (SF) and 30 healthy controls (HC) was evaluated with whole shotgun metagenomic sequencing and 16S rRNA amplicon sequencing, respectively. Stone fragments and intraoperative urine from SF were also analyzed, and urinary oxalate concentrations were determined with HPLC. RESULTS: The findings demonstrate that despite similar dietary micronutrient consumption between the groups, urinary oxalate concentrations were higher in the SF cohort. Alongside these differences, the SF gut microbiota was significantly enriched in Enterobacteriaceae and several presumptive uropathogens, while depleted in microbes known to be beneficial such as Faecalibacterium prausnitzii. The gut microbiota of SFs was also aberrant compared to HC in several metabolic capacities. Importantly, there was no difference between groups in the relative abundance of O. formigenes, nor genes involved in oxalate catabolism including formyl-CoA transferase and oxalyl-CoA decarboxylase. The urinary microbiota was altered between HC and SF, and significantly differed in the SF over time (pre-operative vs. intraoperative urine samples), exhibiting enrichment in pathogenic bacteria following perioperative antibiotic treatment that were similar to those elevated in the SF gut. Interestingly, kidney stones harboured a microbiota distinct from urine, and this was not dictated by the stone's crystalline composition. CONCLUSIONS: Together these findings suggest that the microbiome of SF is dysfunctionally altered in a multimodal manner, aggravating stone formation. The microbiome at multiple body sites, as an interconnected system, likely plays a far more significant role in nephrolithiasis beyond the dogmatic perspective that O. formigenes colonization is the key to stone prevention. Source of Funding: W. Garfield Weston Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e144-e144 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kait Al More articles by this author Benjamin Joris More articles by this author John Denstedt More articles by this author John Chmiel More articles by this author Jennifer Bjazevic More articles by this author Gregory Gloor More articles by this author Hassan Razvi More articles by this author Jeremy Burton More articles by this author Expand All Advertisement Loading ...

PD04-06 SIGNIFICANT POST-PRANDIAL URINARY HYPEROXALURIA OBSERVED BY SPOT TESTING INDIVIDUAL URINARY VOIDS

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I (PD04)1 Apr 2020PD04-06 SIGNIFICANT POST-PRANDIAL URINARY HYPEROXALURIA OBSERVED BY SPOT TESTING INDIVIDUAL URINARY VOIDS William Donelan*, Pedro Espino-Grosso, Tina Esfandiary, Alexandria Voigt, Paul Dominguez-Gutierrez, Cuong Nguyen, and Benjamin Canales William Donelan*William Donelan* More articles by this author , Pedro Espino-GrossoPedro Espino-Grosso More articles by this author , Tina EsfandiaryTina Esfandiary More articles by this author , Alexandria VoigtAlexandria Voigt More articles by this author , Paul Dominguez-GutierrezPaul Dominguez-Gutierrez More articles by this author , Cuong NguyenCuong Nguyen More articles by this author , and Benjamin CanalesBenjamin Canales More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000824.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary oxalate is a vital component of supersaturation profiles and a major driving force for crystallization. Although routinely assessed by metabolic testing, the 24-hour urine collection lacks the ability to measure spikes in urine oxalate concentration, particularly those that follow the consumption of a high oxalate-containing meal. To determine whether oxalate spikes are important for predicting stone risk, we measured oxalate concentration in each void over a 24-hour period in individuals who ingested a high oxalate-containing meal. METHODS: After IRB approval, healthy non-stone formers (6 F, 5 M) were prospectively enrolled to collect consecutively voided urine specimens over a 24-hour period. Participants were given a dietary log and instructed to consume food low in oxalate throughout the entire collection period. At noon on their collection day, participants were asked to consume a high-oxalate load (HOL) in the form of 100g spinach. Participants collected urinary voids in separate containers approximately every 3 hours during the day. Oxalate levels were evaluated on each specimen as well as the final combined 24-hour collection using the Trinity Biotech Oxalate Assay. RESULTS: The 24-hour average urinary oxalate concentrations measured approximately 0.45mM, which is at the normal high end for healthy individuals. We found that within the time period 2-8 hours post-HOL, 43.7% of the daily oxalate excretion occurred, and participants had hyperoxaluric voids that were significantly higher compared to baseline levels or the mean of the entire 24-hour period. CONCLUSIONS: The study demonstrates that significant post-prandial urinary hyperoxaluric spikes occur that are missed using the classical 24-hour urine test. This, together with hyperoxaluria as a potential etiopathological entity in a variety of disease processes, underscores the need for regular temporal-based monitoring of urinary oxalate levels. Source of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award Program and The Endourological Society; and by The National Institutes of Health Grant 5T32DK094789-05. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e80-e80 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Donelan* More articles by this author Pedro Espino-Grosso More articles by this author Tina Esfandiary More articles by this author Alexandria Voigt More articles by this author Paul Dominguez-Gutierrez More articles by this author Cuong Nguyen More articles by this author Benjamin Canales More articles by this author Expand All Advertisement PDF downloadLoading ...

High expression of SLC26A6 in the kidney may contribute to renal calcification via an SLC26A6-dependent mechanism.

BackgroundSolute-linked carrier 26 gene family 6 (SLC26A6), which is mainly expressed in intestines and kidneys, is a multifunctional anion transporter crucial in the transport of oxalate anions. This study aimed to investigate the role of kidney SLC26A6 in urolithiasis.MethodsPatients were divided into two groups: stone formers and nonstone formers. Samples were collected from patients following nephrectomy. Lentivirus with Slc26a6 (lentivirus-Slc26a6) sequence and lentivirus with siRNA-Slc26a6 (lentivirus-siRNA-Slc26a6) sequence were transfected into rats’ kidneys respectively and Slc26a6 expression was detected using Western blot and immunohistochemical analyses. After administering ethylene glycol, oxalate concentration and prevalence of stone formation between the transgenic and control groups were measured using 24-h urine analysis and Von Kossa staining, respectively.ResultsImmunohistochemical and Western blot analyses indicated that stone formers had a significantly higher level of expression of SLC26A6 in the kidney compared with the control group. After lentivirus infection, the urinary oxalate concentration and rate of stone formation in lentivirus-Slc26a6-tranfected rats increased remarkably, while lentivirus-siRNA-Slc26a6-transfected rats showed few crystals.ConclusionThe results showed that high expression levels of renal SLC26A6 may account for kidney stone formation. Downregulating the expression of SLC26A6 in the kidney may be a potential therapeutic target to prevent or treat urolithiasis.

In this issue – July 2017

In this issue – July 2017

Preventive Kidney Stones: Continue Medical Education.

Nephrolithiasis is a common health problem across the globe with a prevalence of 15%–20%. Idiopathic hypercalciuria is the most common cause of nephrolithiasis, and calcium oxalate stones are the most common type of stones in idiopathic hypercalciuric patients. Calcium phosphate stones are frequently associated with other diseases such as renal tubular acidosis type 1, urinary tract infections, and hyperparathyroidism. Compared with flat abdominal film and renal sonography, a noncontrast helical computed tomography scan of the abdomen is the diagnostic procedure of choice for detection of small and radiolucent kidney stones with sensitivity and specificity of nearly 100%. Stones smaller than 5 mm in diameter often pass the urinary tract system and rarely require surgical interventions. The main risk factors for stone formation are low urine output, high urinary concentrations of calcium, oxalate, phosphate, and uric acid compounded by a lower excretion of magnesium and citrate. A complete metabolic workup to identify the risk factors is highly recommended in patients who have passed multiple kidney stones or those with recurrent disease. Calcium oxalate and calcium phosphate stones are treated by the use of thiazide diuretics, allopurinol, and potassium citrate. Strategies to prevent kidney stone recurrence should include the elimination of the identified risk factors and a dietary regimen low in salt and protein, rich in calcium and magnesium which is coupled with adequate fluid intake.

Effects of hydrophilic extract of Nasturtium officinale on prevention of ethylene glycol induced renal stone in male Wistar rats.

Background Nasturtium officinale is a traditional herb that is used for diuresis. Objectives The aim of this study is to determine the effects of hydrophilic extract of Nasturtium officinale on ethylene glycol-induced renal stone in male Wistar rats. Materials and Methods In this study 32 male Wistar rats were randomly divided in six groups and studied during 30 days. Two groups of negative and healthy control received 1% ethylene glycol in water respectively. Low and high dose preventive groups, in addition to 1% ethylene glycol, daily gavaged with 750 mg/kg and 1.5 g/kg of extract respectively. All rats were hold in metabolic cages individually in days 0, 15 and 30 and 24-hour urine samples were collected and checked for urinary parameters of stone formation. In 30th day, rats were anesthetized with ether, and after taking serum sample from them, were sacrificed and their kidneys were sent for pathological evaluation and for presence and volume of calcium oxalate crystals. Results Percentage of calcium oxalate crystals in negative control groups (75%), preventive groups with low dose (28.6%) and high dose (57.1%) in comparison to healthy control group (12.5%) increased (P < 0.05). In 30th day urinary oxalate concentration in preventive and negative control groups were more than healthy control group (P < 0.05). Conclusions This research showed that the Nasturtium officinale extract has no significant effects in urinary and chemical parameters efficient in calcium oxalate stone crystals in rat but its extract in low dose has some preventive effect on renal stone formation.

An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria.

Primary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound.

Enzymatic hydrolysis of phytate and effects on soluble oxalate concentration in foods

Soluble oxalate in foods is major concern for kidney stone formers due to its tendency to increase urinary oxalate concentration. Phytate forms complexes with cations, which increases soluble oxalate by making cations unavailable to precipitate oxalate. Thus, in order to reduce soluble oxalate, bran samples (wheat, oat and barley) and bean samples (red kidney bean and white bean) were treated with phytase. Release of phosphate after phytate degradation and its association with calcium was determined. Phosphate concentration increased after application of phytase in all samples, but effect on soluble oxalate concentration varied. Wheat and oat bran showed significant reduction (P<0.05) in soluble oxalate compared to bean samples. Wheat bran, oat bran and white bean had a lower calcium:phosphate ratio than barley bran and red kidney beans. Correlation of the calcium:phosphate molar ratio with release of phosphate depends on concentration of calcium ions and this influences soluble oxalate concentration.

Effects of oxalate-degrading enzyme on the calcium oxalate kidney stones formation in intestinal hy-peroxaluria rats

Objective To observe the effects of oxalate-degrading enzyme on the formation of calcium oxalate kidney stones in intestinal hyperoxaluria rats. Methods From May to June, 2014, 8 healthy rats were selected as the negative control group named Group A. Intestinal hyperoxaluria rats were randomly divided into three groups (n=8): positive control group (Group B), low-dose enzyme gavage group (Group C) and high-dose enzyme gavage group (Group D). Group A were treated with normal saline by gavage (3 ml/d). Group B were treated with 4% ammonium oxalate solution by gavage (3 ml/d). Group C and Group D were treated with 20 U/d or 40 U/d enzyme on the basis of Group B. The intervention lasted for 4 weeks. The oxalate concentrations of 24 hours urine in each group were detected in 0, 7th, 14th, 21th, 28th day. The renal function, the serum and urine Ca2+ in each group were measured in 0 and 28th day. In 28th day, the kidneys of rats in Group A, B, D were examined by spectral CT. The kidneys of 4 groups were examined microscopically for possible calcium oxalate crystals. Results In 0 day, the urinary oxalate concentrations of Group A, B, C and D were (0.61±0.06), (1.58±0.15), (1.59±0.10) and (1.64±0.20) mmol/L. There were no significant differences among B, C and D(P>0.05). Compared with A, the urinary oxalate concentrations of B, C and D were significantly higher (P<0.001). After the enzyme gavage, the urinary oxalate concentrations of Group C and D were significantly decreased, and Group D decreased more significantly. In 28th day, the urinary oxalate concentrations of Group A, B, C and D were (0.61±0.11), (1.64±0.12), (1.17±0.12) and (0.87±0.11) mmol/L. After statistical analysis, the urinary oxalate concentration of Group C and D were significantly lower than Group B (P<0.01), and Group D decreased more significantly than that in Group C (P<0.01). The CT post-processing workstation data analysis suggested that the average CT value of Group B were significantly higher than D (P<0.01), and both of the two groups were higher than Group A (P<0.01); The differences were more obvious in conditions of low-kilovolt. Renal tubular calcium oxalate crystal deposition were seen the most in Group B, less in Group C and lowest in Group D. Whereas, there was no crystallization in Group A. Conclusion Oxalate-degrading enzymes could inhibit the formation of calcium oxalate kidney stones in intestinal hyperoxaluria rats. Key words: Kidney calculi; Oxalate-degrading enzymes; Hyperoxaluria; Calcium oxalate stones; Rats

2,8-Dihydroxyadenine (DHA) crystalluria – A rare cause of recurrence after kidney transplant

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.

Determination of urine oxalate level in rats with renal calcium oxalate calculus by high-performance liquid chromatography.

To establish a method of high-performance liquid chromatography (HPLC) for determining the urine oxalate levle in rats with renal calcium oxalate calculus. Totally 24 SPF Wistar healthy male rats were randomly divided into control group(n=12)and ethylene glycol (EG) group (n=12). Rats in EG group were administered intragastrically with 2% ammonium chloride (AC)2 ml/rat per day+1% ethylene glycol (EG), along with free access to drinking water.The control group was fed with deionized water, along with the intragastric administration of normal saline (1 ml per day). Twenty-eight days after modelling, the 24-hour urine samples were collected, and the urine oxalic acid levels were determined using HPLC and the results were compared with those of catalytic spectrophotometry using oxidation of methyl. During the HPLC, the samples were separated on Aglient 5TC-C18 (250×4.6 mm,5 Μm), eluted with mixture of methanol (0.1 mol/L) and ammonium acetate (15:85) at 1.2 ml/min, and detected at 314 nm, with the column temperature being 20 ℃. The standard curves of high and low concentrations of oxalic acid were y=5909.1x+378730, R² =0.9984 and y=7810.5x-16635, R² =0.9967,respectively. The lowest detectable concentration in this method was 5 Μg/ml. The linear high concentration range of oxalate stood at 62.50-2000.00 Μg/ml, and the linear low concentration range of oxalate stood at 6.25-100.00 Μg/ml. Its average recovery was 95.1%, and its within-day and day-to-day precisions were 3.4%-10.8% and 3.8%-9.4%. Both HPLC and catalytic spectrophotometry showed significantly higher urinary oxalic acid concentration and 24 h urine oxalate level in EG group compared with the control group [urinary oxalic acid concentration: (736.35 ± 254.52) Μg/ml vs.(51.56 ± 36.34) Μg/ml,(687.35 ± 234.53) Μg/ml vs.(50.24 ± 42.34) Μg/ml;24 h urine oxalate level: (11.23 ± 4.12)mg vs.(0.87 ± 0.45)mg,(9.89 ± 3.55)mg vs. (0.77 ± 0.65)mg; all P<0.01]. No statistically significant difference was observed in the results of urinary oxalate concentration and 24 h urine oxalate level between HPLC and potassium chromate oxidation of methyl red spectrophotometry (all P>0.05). HPLC is a simple, rapid, and precise method in detecting urine oxalate level in rats with renal calcium oxalate calculus, with high recovery rate.

Biochemical and Pathological Study of Hydroalcoholic Extract of Achillea millefolium L. on Ethylene Glycol-Induced Nephrolithiasis in Laboratory Rats.

Background:Nephrolithiasis is of the most prevalent urinary tract disease. It seems worthwhile to replace the conventional treatments with more beneficial and safer agents, particularly herbal medicines which are receiving an increasing interest nowadays.Aims:In this study, we investigated the protective and curative effects of Achillea millefolium L. on ethylene glycol (EG)-induced nephrolithiasis in rats.Materials and Methods:The extract of A. millefolium was prepared by soxhlet method. Forty male Wistar rats were randomly divided into five groups (N = 8) as follows. The negative control (group A) received tap drinking water. Rats in sham (positive control group B), curative (group C and D), and preventive (group E) groups all received 1% EG in drinking water according to the experimental protocol for 30 days. In the curative groups, dosages of 200 and 400 mg/kg body weight (BW) of A. millefolium extract were administered orally from day 15 to the end of the experiment, group C and D, respectively. Group E received 200 mg/kg A. millefolium extract from the 1st day throughout the experiment. Urinary oxalate and citrate concentrations were measured by spectrophotometer on the first and 30th days. On day 31, the kidneys were removed and examined histopathologically for counting the calcium oxalate (CaOx) deposits in 50 microscopic fields.Results:In the curative and preventive groups, administration of A. millefolium extract showed significant reduction in urinary oxalate concentration (P < 0.05). Also, urinary citrate concentration was significantly increased in group C, D, and E. The CaOx deposits significantly decreased in group C to E compared with the group B.Conclusions:According to our results, A. millefolium extract had preventive and curative effects on EG-induced renal calculi.

Effects of potassium chloride and potassium bicarbonate in the diet on urinary pH and mineral excretion of adult cats

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.

Quiz Page August 2013: Kidney Failure in a Transplant From an Identical Twin

Quiz Page August 2013: Kidney Failure in a Transplant From an Identical Twin

Is polycystic ovarian syndrome a risk factor for urolithiasis?

Urinary stone disease is a complex multifactorial disorder influenced by both intrinsic and environmental factors. It is generally known that age and sex are risk factors for urinary stone disease. Also men have higher mean urinary oxalate concentrations than women. In addition, in animal and human studies, testosterone has been shown to increase the formation of urinary stones. This suggests that sex hormones are considered to be involved in the pathogenesis of stone disease. Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders of women in the reproductive age, affecting 5-10% of women in this life span. It is characterized with chronic anovulation\oligo-ovulation, clinical or biochemical evidence of hyperandrogenism and polycystic ovaries on ultrasound examination. Hyperandrogenism, the main feature of PCOS, may trigger the urinary stone formation besides hirsutism, alopecia and acne. Therefore, we hypothesize that PCOS accompanied by hyperandrogenism may be a risk factor in the formation of urinary stone disease.

Lanthanum Carbonate Inhibits Intestinal Oxalate Absorption and Prevents Nephrocalcinosis After Oxalate Loading in Rats

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.