Urinary Calcium Oxalate Research Articles

Serum antioxidant enzyme levels are decreased in patients with urinary calcium oxalate stones.

To compare the serum antioxidant enzyme levels between patients with urinary stone disease and healthy volunteers to determine the effect of cellular oxidative stress on urinary calcium oxalate stones formation.Materials & Methods: A total of 51 patients with proven urinary calcium oxalate stones (female 35.3%, mean age: 49.3 years) and 37 healthy subjects (female 45.9%, mean age: 44.1 years) were included. The serum levels of antioxidant catalase, glutathione peroxidase, superoxide dismutase and lipid peroxidation were measured in serum samples taken from the peripheral venous circulation. Mean serum catalase level of patient group was insignificantly higher than healthy subjects (7.54 mmol- H2O2/mg/sec versus 6.16 mmolH2O2/mg/sec, respectively; P = .06) whereas mean superoxide dismutase level (1.56 U/ml versus 3.86 U/ml, P = .047), glutathione peroxidase level (6.70 U/ml versus 8.19 U/ml, P = .022) and lipid peroxidation level (2.35 nmol/ml versus 3.31 nmol/ml, P = .034) of patient group were significantly lower than healthy subjects. Patients with family history of urinary stone disease had significantly lower mean serumlevels of catalase (P = .037), superoxide dismutase (P = .047) and glutathione peroxidase (P = .01), compared with patients without family history. The findings of this study provide evidence regarding the role of oxidative stress in the development of urinary calcium oxalate stones. Future clinical trials are necessary to elucidate the actual mechanisms of the calcium oxalate stone formation in the environment with increased oxidative stress.

Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats

Urolithiasis is a painful disorder in which stones are formed in the kidney, bladder or urethra. There are no proper therapeutic treatments available for kidney stones and people suffering from larger stones have to undergo surgery which has many side effects. A natural remedy with therapeutic effects that can dissipate and remove even the larger stones would eliminate the need of a surgery and the risks associated with it. The flowers of Phlogacanthus thyrsiformis used in culinary recipes in the north eastern India are also widely used as a folklore medicine for the treatment of kidney stones and liver disorders. The aim of this study was to evaluate the prophylactic and therapeutic activity of the aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles against struvite urinary stones and calcium oxalate kidney stones. A kidney stone inhibition study was carried out on struvite stones grown in gel medium and calcium oxalate stones in rat models using an aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles. The aqueous extract of P. thyrsiformis flowers and their biofabricated silver nanoparticles, obtained by a green synthetic method, were used to treat struvite urinary stones in vitro and calcium oxalate kidney stones in vivo. Struvite stones were grown in tubes by gel diffusion technique and were treated with varying concentrations of the extract and its nanoparticles. The size of the struvite stones was monitored for 96h using a travelling microscope. Calcium oxalate stones were induced in male Wistar rats by feeding ethylene glycol-ammonium chloride mixture for 14days. Both, prophylactic and therapeutic activities were evaluated by analyzing the urine, serum and histopathological parameters of the rats. The qualitative screening of water extract unveiled the presence of flavonoids as a major constituent. Both, the extract and the nanoparticles effectively reduced the size of struvite stones in vitro and eliminated calcium oxalate stones in Wistar rats in vivo. The potent therapeutic activity of both extract and silver nanoparticles was observed as compared to preventive activity. Anti-urolithiatic potency can be attributed to the presence of flavonoids.

Nephrolithiasis

Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment. This review contains 5 highly rendered figure, 3 tables, and 105 references.

Combination of vitamin E and vitamin C alleviates renal function in hyperoxaluric rats via antioxidant activity.

Hyperoxaluria and oxidative stress are risk factors in calcium oxalate (CaOx) stone formation. Supplement with antioxidant could be effective in prevention of recurrent stone formation. The present study aims to evaluate the protective effects of vitamin E and vitamin C in hyperoxaluric rat. The experiment was performed in rats for 21 days. Rats were divided into 5 groups as follows: control (group 1, n=8), hyperoxaluric rats (group 2, n=8), hyperoxaluric rats with vitamin E supplement (group 3, n=7), hyperoxaluric rats with vitamin C supplement (group 4, n=7) and hyperoxaluric rats with vitamin E and C supplement (group 5, n=7). Hyperoxaluria was induced by feeding hydroxyl L-proline (HLP) 2% w/v dissolved in drinking water. Intraperitoneal 200 mg/kg of vitamin E was given in groups 3 and 5 on days 1, 6, 11 and 16, while 500 mg of vitamin C was injected intravenously in groups 4 and 5 on days 1 and 11. Renal functions and oxidative status were measured. The urinary oxalate excretion was increased in HLP supplement rats, while glomerular filtration rate, proximal water and sodium reabsorption were significantly lower in group 2 compared with a control (P<0.05). Giving antioxidants significantly lower urinary calcium oxalate crystals (P<0.05). Hyperoxaluric rats had higher plasma malondialdehyde (PMDA) and lower urinary total antioxidant status (UTAS), which were alleviated by vitamin E and/or vitamin C supplement. In conclusion, giving combination of vitamin E and vitamin C exerts a protective role against HLP-induced oxalate nephropathy.

Prevalence of Urinary Calcium Oxalate and other Urine Microscopic Parameters among Secondary School Students in Bali, Nigeria

Prevalence of Urinary Calcium Oxalate and other Urine Microscopic Parameters among Secondary School Students in Bali, Nigeria

The paradoxical role of urinary macromolecules in the aggregation of calcium oxalate: a further plea to increase diuresis in stone metaphylaxis.

This study was designed to get information on aggregation (AGN) of urinary calcium oxalate crystals (CaOx) which seems to occur in stone formation despite a protecting coat of urinary macromolecules (UMs). CaOx crystallization was directly produced in urine, control and albumin solution by Ox titration and was spectrophotometrically followed. A rapid decrease of optical density indicating AGN was absent in 14 of 15 freshly voided urines of 5 healthy controls. However, in the presence of UM-coated hydroxyapatite all urines with relative high sodium concentration, being an indicator of concentrated urine, showed a pronounced AGN which was abolished when these urines were diluted. Albumin relatively found to be an inhibitor of AGN showed after temporary adsorption on Ca Phosphate (CaP) massive self-AGN and changed to a promoter of CaOx AGN. Self-AGN after adsorption on surfaces especially of CaP, being an important compound of Randall’s plaques, can thus explain this paradoxical behavior of UMs. Aggregated UMs probably bridge zones of electrostatic repulsion between UM-coated crystals with identical electrical surface charge. These zones extend by urine dilution which decreases ionic strength. Diminution of urinary concentration by increasing diuresis seems, therefore, to be important in stone metaphylaxis.

Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations

Some patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should decrease urinary supersaturation of stone forming solutes, although this action has never been proved. We conducted a double-blind, randomized, placebo controlled, crossover study of 21 calcium urinary stone formers stratified into majority calcium oxalate (10 patients) and calcium phosphate (11) groups. Patients received 45 mg tolvaptan per day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24-hour urine sample was collected at the end of weeks 1 and 3. Tolvaptan vs placebo decreased urinary osmolality (mean ± SD 204 ± 96 vs 529 ± 213 mOsm/kg, p <0.001) and increased urinary volume (4.8 ± 2.9 vs 1.8 ± 0.9 L, p <0.001). The majority of urinary solute excretion rates, including sodium and calcium, did not change significantly, although oxalate secretion increased slightly (from mean ± SD 15 ± 8 to 23 ± 8 mg per 24 hours, p = 0.009). Mean ± SD urinary calcium oxalate supersaturation (-0.01 ± 1.14 vs 0.95 ± 0.87 dG, p <0.001), calcium phosphate supersaturation (-1.66 ± 1.17 vs -0.13 ± 1.02 dG, p <0.001) and uric acid supersaturation (-2.05 ± 4.05 vs -5.24 ± 3.12 dG, p=0.04) all dramatically decreased. Effects did not differ between the calcium oxalate and calcium phosphate groups (p >0.05 for all interactions). Tolvaptan increases urine volume and decreases urinary supersaturation in calcium stone formers. Further study is needed to determine if long-term use of V2 receptor antagonists results in fewer stone events.

Proinflammatory and Metabolic Changes Facilitate Renal Crystal Deposition in an Obese Mouse Model of Metabolic Syndrome

To clarify metabolic syndrome induced stone formation mechanisms we investigated the metabolic and immunohistochemical characteristics associated with renal crystal deposition using a model of mice with metabolic syndrome administered a high fat diet and ethylene glycol. Ob/Ob mice with Leptin gene deficiencies and metabolic syndrome related characteristics were compared with wild heterozygous lean mice. Four study groups were fed standard food and water (control group), a high fat diet and normal water (high fat diet group), 1% ethylene glycol and standard food (ethylene glycol group) or a high fat diet and 1% ethylene glycol (high fat diet plus ethylene glycol group). Blood, urine and kidney samples were taken after 14 days. Ob/Ob mice in the high fat diet plus ethylene glycol group showed diffuse renal crystal depositions. Lean and Ob/Ob mice in the high fat diet plus ethylene glycol group showed significant excretion of urinary calcium oxalate crystals. Ob/Ob mice had significant hypercalciuria, hyperphosphaturia and hyperlipidemia, massive lipid fragments in tubular lumina and fat droplets in renal tubular cells. Ob/Ob mice in the high fat diet plus ethylene glycol group hadmarkedly increased expression of osteopontin, monocyte chemoattractant protein-1, interleukin-6 and tumor necrosis factor-α. In Ob/Ob mice the number of proinflammatory macrophages was considerably elevated. We induced renal crystal deposition in mice with metabolic syndrome using a high fat diet and ethylene glycol. Increases in luminal mineral and lipid density, and proinflammatory adipocytokines and macrophages facilitated renal crystal formation in mice with metabolic syndrome.

Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria.

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.

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.

Effects of calcium and magnesium concentrations in drinking water on renal lithogenesis and metabolism in rats with relative hyperoxaluria

Objective To investigate the effects of different calcium and magnesium concentration ratios in drinking water on renal lithogenesis and metabolism in rats with ethylene glycol(EG)-induced relative hyperoxaluria.Methods Normal SD rats were exposed to 0.1% EG and different Ca2+and Mg2+concentration ratios(360/10,120/10,10/10,10/40,and 10/80,in mg/L)in drinking water for 8weeks.After the treatments,24 hurine volume and oxalate,citrate,Ca2+,and Mg2+levels were measured,and the serum creatinine,blood urea nitrogen(BUN),Ca2+,and Mg2+levels and renal pathologies were examined.Results No significant differences were found among the groups in body weight,water intake,24 hurine volume,24 hurinary citrate excretion,blood Ca2+and Mg2+levels,or serum creatinine.Ca/Mg ratios of 10/10 and 10/40 in drinking water caused a significant increase in kidney weight(P0.05),and the latter was associated with significantly increased 24 h urinary Mg2+excretion as compared with the normal control group(P0.05).BUN was significantly higher in Ca/Mg(10/40)group than in the normal control and model groups(P0.05).The model group and Ca/Mg groups(120/10,10/10and10/40)all showed significantly increased urinary oxalate excretion compared with the normal control group(P0.05 or 0.01);except for Ca/Mg(10/10)group,all the other treatment groups had significantly lower oxalate excretion than the model group(P0.01).None of the groups showed detectable crystal deposition or renal pathologies.Conclusion Relative hyperoxaluria does not affect calcium and magnesium metabolism or the formation of lithogenesis and urinary calcium oxalate crystals in rats.Increased Ca2+and Mg2+concentrations that are below the limits in hard water can cause decreased 24 hurinary oxalate excretion.In uncomplicated hyperoxaluria,only a sufficiently high oxalate concentration can lead to lithogenesis.Urinary citrate is not affected by Ca2+or Mg2+ratios in drinking water.

Recurrence of crystalline nephropathy after kidney transplantation in APRT deficiency and primary hyperoxaluria.

Purpose of reviewTo provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients.Source of informationPubmed literature search.SettingPrimary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria) that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD) and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation.Key messagesPatients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis). We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR) and a history of kidney stones. In APRT deficiency, stones may be confused with uric acid stones, unless specialized techniques are used (infrared spectroscopy or X-ray crystallography for urinary crystals or stone analysis; Fourier transform infrared microscopy for crystals in kidney biopsy). Where these are unavailable, and for confirmation, the diagnosis can be made by measurement of enzyme activity in red blood cell lysates or by genetic testing. In patients with primary hyperoxaluria, levels of urinary and plasma oxalate; and the presence of nearly pure calcium oxalate monohydrate in stones, which often also have an unusually pale colour and unorganized structure, increase diagnostic suspicion. Molecular genetic testing is the criterion measure. Lifelong allopurinol therapy, with high fluid intake if appropriate, may stabilize kidney function in APRT deficiency; if ESRD has occurred or is near, results with kidney transplantation after initiation of allopurinol are excellent. In primary hyperoxaluria recognized before ESRD, pyridoxine treatment and high fluid intake may lead to a substantial decrease in urinary calcium oxalate supersaturation and prevent renal failure. In non-responsive patients or those recognized later in their disease, liver transplantation cures the underlying defect and should be considered when the GFR falls below 30 ml/min/1.73 m2; in those which or near ESRD, liver transplantation and intensive dialysis before kidney transplantation may be considered to reduce the total body oxalate burden before kidney transplantation.LimitationsThe availability of diagnostic tests varies between countries and centres. Data on long term outcomes after kidney transplantation are limited, especially for APRT deficiency patients.ImplicationsIncreasing transplant physicians knowledge of APRT deficiency and primary hyperoxaluria should enable them to implement adequate diagnostic and therapeutic interventions, thereby achieving good outcomes after kidney transplantation.

Treatment of calcium nephrolithiasis in the patient with hyperuricosuria

Nearly one-third of patients with calcium stones have hyperuricosuria. In vitro studies and clinical trials have investigated the relationship between uric acid and calcium stones, but the association between hyperuricosuria and calcium stone formation in patients is still being debated. Uric acid appears to cause salting out of calcium oxalate in human urine. However, the importance of this in vitro phenomenon to the proposed association is not supported in cross-sectional observational studies. A small placebo-controlled randomized clinical trial showed that allopurinol decreased the rate of recurrent calcium oxalate calculi in patients with hyperuricosuria and normocalciuria. An assessment of the effect of combination therapy of allopurinol with indapamide showed no additive effect. Allopurinol may have antioxidant effects that are responsible for its reducing calcium stone formation, which are independent of xanthine oxidase inhibition. In addition, a newer xanthine oxidoreductase inhibitor, febuxostat, may also be effective in the prevention of calcium stones, as it reduces urinary uric acid excretion.

Herbal preparations affect the kinetic factors of calcium oxalate crystallization in synthetic urine: implications for kidney stone therapy

Herbal remedies are increasingly being considered as suitable long-term treatments for renal dysfunction. The objective of the present study was to investigate the effect of some herbal extracts, all previously identified in published studies as influencing kidney stone formation, on the crystallization characteristics of calcium oxalate (CaOx) in synthetic urine (SU). Five herbal extracts were selected for the study: Folium pyrrosiae, Desmodium styracifolium, Phyllanthus niruri, Orthosiphon stamineus and Cystone(®). Concentrated stock solutions of each herbal extract were prepared and were tested at their recommended dosages inin vitro crystallization studies in SU. CaOx crystallization experiments were performed in which the metastable limit (MSL), average particle size, and nucleation and growth rates were determined. The CaOx MSL of SU was unaltered by the five herbal extracts. Three of the herbs (Desmodium styracifolium, Orthosiphon stamineus and Cystone(®)) significantly reduced the average particle size of precipitated crystals relative to undosed SU. All of the extracts increased the rate of nucleation and decreased the rate of growth significantly in SU. Cystone(®) showed the greatest effect on the measured risk factors. It is concluded that all of the herbs have the potential to serve as inhibitors of calcium oxalate stone formation and warrant investigation in clinical trials.

Urinary Lithogenic Risk Profile in Recurrent Stone Formers With Hyperoxaluria: A Randomized Controlled Trial Comparing DASH (Dietary Approaches to Stop Hypertension)-Style and Low-Oxalate Diets

Patients with nephrolithiasis and hyperoxaluria generally are advised to follow a low-oxalate diet. However, most people do not eat isolated nutrients, but meals consisting of a variety of foods with complex combinations of nutrients. A more rational approach to nephrolithiasis prevention would be to base dietary advice on the cumulative effects of foods and different dietary patterns rather than single nutrients. Randomized controlled trial. Recurrent stone formers with hyperoxaluria (urine oxalate > 40 mg/d). The intervention group was asked to follow a calorie-controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high in fruit, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas the control group was prescribed a low-oxalate diet. Study length was 8 weeks. Primary: change in urinary calcium oxalate supersaturation. Changes in 24-hour urinary composition. 57 participants were randomly assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend for urinary oxalate excretion to increase in the DASH versus the low-oxalate group (point estimate of difference, 9.0mg/d; 95% CI, -1.1 to 19.1mg/d; P=0.08). However, there was a trend for calcium oxalate supersaturation to decrease in the DASH versus the low-oxalate group (point estimate of difference, -1.24; 95% CI, -2.80 to 0.32; P=0.08) in association with an increase in magnesium and citrate excretion and urine pH in the DASH versus low-oxalate group. Limited sample size, as-treated analysis, nonsignificant results. The DASH diet might be an effective alternative to the low-oxalate diet in reducing calcium oxalate supersaturation and should be studied more.

Effect of Unitary, Binary and Ternary Carboxylates on Crystallization Kinetics of Calcium Oxalate in Artificial Urine

Effect of Unitary, Binary and Ternary Carboxylates on Crystallization Kinetics of Calcium Oxalate in Artificial Urine

Anti-nephrolithic potential of resveratrol via inhibition of ROS, MCP-1, hyaluronan and osteopontin in vitro and in vivo

BackgroundThough resveratrol is known to have anti-cancer, anti-diabetic, anti-oxidant and anti-inflammatory activities, the inhibitory mechanism of resveratrol in kidney stone formation has not been elucidated so far. MethodELISA, flow cytometry, RT-PCR, and western blotting were performed. Human renal epithelial cells (HRCs) and rats with ethylene glycol (EG)-induced kidney stones were used. ResultsA wound healing assay revealed that resveratrol significantly inhibited the oxalate-mediated migration of HRCs, considering oxalate mediates kidney stone formation. Also, resveratrol suppressed the mRNA expression of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunits such as p22phox and p47phox, monocyte chemoattractant protein 1 (MCP-1) and osteopontin (OPN) in oxalate-treated HRCs. Furthermore, western blotting showed that resveratrol downregulated the expression of MCP-1-related proteins including transforming growth factor(TGF-β1), TGFR-I or II and hyaluronan in oxalate-treated HRCs. Consistently, resveratrol reduced oxalate-mediated production of reactive oxygen species (ROS) and malondialdehyde (MDA) in oxalate-treated HRCs, while the activities of anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were enhanced by resveratrol in HRCs and EG-treated kidneys of rats. Consistently, resveratrol significantly reduced the number of urine calcium oxalate crystals and serum MD A, and attenuated the expression of OPN and hyaluroran in EG-treated rats. ConclusionsOur findings suggest that resveratrol exerts anti-nephrolithic potential via inhibition of ROS, MCP-1 hyaluronan and OPN signaling.

Using 24-Hour Urinalysis to Predict Stone Type

We determined the accuracy of 24-hour urinalysis in predicting stone type and identify the associations between 24-hour urine elements with stone type. We performed a retrospective review of 503 stone formers with stone composition analysis and 24-hour urinalysis available. Analysis of 24-hour urine elements across stone types was performed using Fisher's exact test and ANOVA. Multinomial logistic regression was used to predict stone type based on 24-hour urinalysis. A total of 280 (56%) patients had predominantly calcium oxalate, 103(20%) had uric acid, 93 (19%) had calcium phosphate, 16 (3%) had mixed and 11(2%) had other stone types. There were several significant patient characteristics and 24-hour urinalysis differences across stone type groups. The statistical model predicted 371 (74%) calcium oxalate, 78 (16%) uric acid, 52 (10%) calcium phosphate, zero mixed and 2 (less than 1%) other stone types. The model correctly predicted calcium oxalate stones in 85%, uric acid in 51%, calcium phosphate in 31%, mixed in 0% and other stone types in 18% of the cases. Of the predicted stone types, correct predictions were 61%, 69%, 56% and 71% for calcium oxalate, uric acid, calcium phosphate and other stones types, respectively. The overall accuracy was 64%. Plots were used to explore the associations between each 24-hour urine element with each predicted stone type adjusted for all the others urinary elements. A 24-hour urinalysis alone does not accurately predict stone type. However, it may be used in conjunction with other variables to predict stone composition.

Sensitivity and specificity of 24-hour urine chemistry levels for detecting elevated calcium oxalate and calcium phosphate supersaturation

The gold standard for determining likelihood of calcium oxalate (CaOx) and calcium phosphate (CaPhos) stone formation in urine is supersaturation of CaOx and CaPhos. Our objective was to investigate whether traditional measurement of total calcium, oxalate and phosphate in a 24-hour urine collection is sufficiently sensitive and specific for detecting elevated supersaturation to preclude the more expensive supersaturation test. We performed a retrospective review of 150 consecutive patients with nephrolithiasis who underwent measurement of CaOx supersaturation (CaOxSS) and CaPhos supersaturation (CaPhosSS), as well as total calcium, oxalate and phosphate in a 24-hour urine collection. We used various cut-off values to determine sensitivity and specificity of 24-hour urine measurements for detecting elevated CaOxSS and CaPhosSS. In men and women, the sensitivity of 24-hour calcium for detecting elevated CaOxSS was 71% and 79%, respectively; for oxalate, sensitivity was 59% and 36%, respectively. In men and women, the sensitivity of 24-hour calcium for detecting elevated CaPhosSS was 74% and 88%, respectively; for phosphate, sensitivity was 57% and 8%, respectively. In men and women, the specificity of 24-hour calcium for detecting elevated CaOxSS was 55% and 48%, respectively; it was 60% for detecting elevated CaPhosSS in both men and women. Traditional 24-hour urine analysis is sensitive, but not specific, for detecting elevated CaOxSS and CaPhosSS. Most patients with abnormal 24-hour urine analysis have normal supersaturation, and treatment decisions based on traditional urine analysis would lead to overtreatment in these patients.

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.