oxalates and Proteinuria

Topics: Acidosis, Renal Tubular; Amino Acids; Calcium; Carbohydrate Dehydrogenases; Carrier Proteins; Chloride Channels; Cystinuria; Humans; Hyperoxaluria, Primary; Hypoxanthine Phosphoribosyltransferase; Mutation; Organic Anion Transporters; Organic Cation Transport Proteins; Oxalates; Proteinuria; Proton-Translocating ATPases; Purines; Transaminases; Uric Acid; Urinary Calculi

The understanding of the formation of urinary stones centers around three main mechanisms: the urinary concentration of stone-forming ions, the role of promoters, and the role of inhibitors of crystal formation and crystal aggregation. With respect to the promoting activity, lately emphasis has shifted from the role of the organic matrix to that of one salt inducing by epitaxy the precipitation of another salt. Among the inhibitors, it has become necessary to distinguish between those affecting crystal formation and those affecting crystal aggregation. For measuring the inhibitory activity, the various techniques and their relevance have been reviewed. It has been found that the main inhibitors for calcium phosphate and calcium oxalate precipitation are citrate, pyrophosphate, and perhaps magnesium. Those for calcium phosphate and calcium oxalate aggregation are glycosaminoglycans, pyrophosphate, and citrate. Among the synthetic inhibitors, the diphosphonates are the most powerful for both processes. The role and the therapeutic implications of these various concepts have been discussed.

Topics: Animals; Calcium; Calcium Phosphates; Crystallization; Diphosphonates; Humans; Oxalates; Proteinuria; Urinary Calculi

Topics: Africa; Asia; Calcium; Chemical Precipitation; Child; Child, Preschool; Chronic Disease; Depression, Chemical; Ethnicity; Europe; Female; Humans; Infant; Kidney Calculi; Lymphatic Diseases; Magnesium; Male; Methylene Blue; Mucoproteins; Oxalates; Phosphates; Protein Binding; Proteinuria; Recurrence; Sex Factors; Sodium; Solubility; United States; Urinary Bladder Calculi

One of the obstacles in analyzing frozen urine samples is the formation of uncharacterized precipitates. Frequently, these precipitates are discarded before analysis. Some laboratory data may be erroneous if these precipitates contain important compounds. In the present study, we examined urinary sediments precipitated after overnight storage at -20 degrees C. Although cells and debris were removed before freezing, the precipitates remained, whereas storing the centrifuged urine overnight at 4 degrees C did not result in precipitate formation. There were no significant differences observed among 10 healthy individuals (5 men and 5 women). EDTA (5 mM) could efficiently reduce the amount of precipitates to approximately 25% of the initial amount. The addition of exogenous CaCl2, but not sodium oxalate and NaCl, significantly increased the amount of precipitates in a dose-dependent manner. Linear regression analysis revealed a significant correlation between endogenous urinary calcium level and the amount of precipitates (r = 0.894; P < 0.001). Urine pH also had some effects on the type and amount of precipitates. These precipitates were composed mainly of calcium oxalate dihydrate and amorphous calcium crystals. The results also showed that these precipitates could deplete urinary proteins and calcium ions (23.6 +/- 1.1% decrease). Therefore, these freezer-induced urinary sediments significantly affect protein analysis and measurement of calcium levels in the urine. However, vigorous shaking of the sample at room temperature could redissolve these precipitates. Our data strongly indicate that these freezer-induced precipitates must be taken into account when the frozen urine samples are analyzed.

Topics: Adult; Calcium Chloride; Centrifugation; Female; Freezing; Humans; Hydrogen-Ion Concentration; Male; Oxalates; Proteinuria; Sodium Chloride; Specimen Handling; Urine

In carcinogenicity studies with PPAR gamma and alpha/gamma agonists, urinary bladder tumors have been reported in Harlan Sprague-Dawley (HSD) and Charles River Sprague-Dawley (SD) but not Wistar (WI) rats, with urolithiasis purported to be the inciting event. In two 3-month studies, the authors investigated strain-related differences in urine composition by sampling urine multiple times daily. Urine pH, electrolytes, creatinine, protein, citrate and oxalate levels, and serum citrate were assessed; urine sediment was analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. HSD rats had significantly higher urine calcium than SD or WI rats, primarily as calcium phosphate-containing precipitate. When compared to SD rats, HSD rats had lower urine volume, higher urine protein, and a comparable (week 4) to lower (week 13) burden of MgNH(4)PO(4) aggregates. Relative to WI rats, HSD rats had higher urine protein and magnesium and lower serum and urine citrate. Overall, the susceptibility to urolithiasis in male rats was HSD > SD > WI; this was likely due to strain-related differences in the amount of urine protein (a nidus for crystal formation), lithogenic ions, citrate (an inhibitor of lithogenesis), and/or volume. Strain-related differences in urine composition need to be considered when interpreting the outcome of studies with compounds that alter urine composition.

Topics: Animals; Calcium; Calcium Phosphates; Citrates; Creatinine; Electrolytes; Hydrogen-Ion Concentration; Magnesium; Magnesium Compounds; Male; Microscopy, Electron, Scanning; Oxalates; Phosphates; Proteinuria; Rats; Rats, Sprague-Dawley; Rats, Wistar; Species Specificity; Spectrometry, X-Ray Emission; Struvite; Urinalysis; Urolithiasis

A 65-year-old Japanese male developed renal dysfunction, showing proteinuria and marked urinary excretion of beta2-microglobulin. He had consumed approximately 100-200 g peanuts and 750-1,000 ml beer every day for two or three months. He had previously been treated for hypertension with an angiotensin-converting enzyme inhibitor, enalapril. He then visited his primary-care doctor with mild fever, and renal dysfunction with mild diabetes mellitus were diagnosed. He was referred to our hospital, and because no diabetic retinopathy was observed by ophthalmological tests, renal biopsy examination was performed to clarify renal dysfunction. Renal biopsy specimens showed intimal thickening in the small arteries and interstitial nephritis with a granulomatous lesion, accompanied by oxalate crystals under polarized light. Glomeruli were unremarkable without any immunoglobulin deposition, and nodular lesions. Because he daily consumed a large amount of peanuts, oxalate nephropathy due to excessive intake of peanuts was strongly suspected. This case revealed that unusual food habits, including nuts, can cause oxalate nephropathy, and that close examination by renal biopsy was useful for clarifying the etiology of the unknown renal damage.

Topics: Aged; Arachis; beta 2-Microglobulin; Biopsy; Humans; Kidney; Male; Nephritis, Interstitial; Oxalates; Proteinuria

Muraglitazar, a PPARalpha/gamma agonist, dose-dependently increased urinary bladder tumors in male Harlan Sprague-Dawley (HSD) rats administered 5, 30, or 50 mg/kg/day for up to 2 years. To determine the mode of tumor development, male HSD rats were treated daily for up to 21 months at doses of 0, 1, or 50 mg/kg while being fed either a normal or 1% NH4Cl-acidified diet. Muraglitazar-associated, time-dependent changes in urine composition, urothelial mitogenesis and apoptosis, and urothelial morphology were assessed. In control and treated rats fed a normal diet, urine pH was generally > or = 6.5, which facilitates formation of calcium-and magnesium-containing solids, particularly in the presence of other prolithogenic changes in rat urine. Urinary citrate, an inhibitor of lithogenesis, and soluble calcium concentrations were dose dependently decreased in association with increased calcium phosphate precipitate, crystals and/or microcalculi; magnesium ammonium phosphate crystals and aggregates; and calcium oxalate-containing thin, rod-like crystals. Morphologically, sustained urothelial cytotoxicity and proliferation with a ventral bladder predilection were noted in treated rats by month 1 and urinary carcinomas with a similar distribution occurred by month 9. Urothelial apoptotic rates were unaffected by muraglitazar treatment or diet. In muraglitazar-treated rats fed an acidified diet, urine pH was invariably < 6.5, which inhibited formation of calcium-and magnesium-containing solids. Moreover, dietary acidification prevented the urothelial cytotoxic, proliferative, and tumorigenic responses. Collectively, these data support an indirect pharmacologic mode of urinary bladder tumor development involving alterations in urine composition that predispose to urolithiasis and associated decreases in urine-soluble calcium concentrations.

Topics: Animals; Antimetabolites; Apoptosis; Area Under Curve; Bromodeoxyuridine; Calcium; Carcinogens; Cell Proliferation; Citrates; Electrolytes; Glycine; Hydrogen-Ion Concentration; Immunohistochemistry; Male; Microscopy, Electron, Scanning; Organ Size; Oxalates; Oxazoles; Phosphates; PPAR alpha; PPAR gamma; Proteinuria; Rats; Rats, Sprague-Dawley; Spectrometry, X-Ray Emission; Urinary Bladder Neoplasms; Urolithiasis; Urothelium

In idiopathic recurrent urolithiasis (IRCU) calcium oxalate and calcium phosphate are components of stones. It is not sufficiently known whether in urine the nucleation (liquid-solid transition) of each salt requires a different environment, if so which environment, and whether there is an impact on stone formation. Nucleation was induced by in vitro addition of oxalate or calcium to post-test meal load whole urine of male stone patients (n=48), showing normal daily and baseline fasting oxaluria. The maximally tolerated (until visible precipitates occur) concentration of oxalate (T-Ox) or calcium (T-Ca) was determined; additionally evaluated were other variables in urine, including total, complexed and free citrate (F-Cit), protein (albumin, non-albumin protein) and the clinical intensity (synonymous metabolic activity; MA) of IRCU. In the first of three trials the accumulation of substances in stone-forming urine was verified (trial-V); in the second (clinical trial 1) two strata of T-Ox (Low, High) were compared; in the third (clinical trial 2) IRCU patients (n=27) and a control group (n=13) were included to clarify whether in stone-forming urine the first crystal formed was calcium oxalate or calcium phosphate, and to identify the state of F-Cit. T-Ox was studied at the original pH (average < 6.0), T-Ca at prefixed pH 6.0; the precipitates were subjected to electron microscopy and element analysis. Trial-V: Among the urinary substances accumulating at the indicated pHs were calcium, oxalate and phosphate, and the crystal-urine ratios were compatible with the nucleation of calcium oxalate, calcium-poor and calcium-rich calcium phosphate; citrate, protein and potassium also accumulated. Clinical trial 1: the two strata exhibited an inverse change of T-Ox and T-Ca, the ratio T-Ox/T-Ca and MA. The initial (before induction of Ox or Ca excess) supersaturation of calcium oxalate and brushite were unchanged, with the difference of proteinuria being borderline. Several correlations were significant (p < or = 0.05): urine pH with citrate and volume, protein with volume and MA, T-Ox with T-Ca and MA. Clinical trial 2: in patients with reduced urine volume and moderate urine calcium excess, the first precipitate appeared to be calcium oxalate, followed by amorphous calcium phosphate. Conversely, when the calcium excess was extreme, calcium-rich hydroxyapatite developed, followed by calcium oxalate; F-Cit, not total and complexed citrate, was decreased in IRCU vs.

Topics: Adult; Aged; Calcium; Calcium Chloride; Calcium Oxalate; Calcium Phosphates; Citric Acid; Creatine; Crystallization; Crystallography; Data Interpretation, Statistical; Electron Probe Microanalysis; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Oxalates; Phosphates; Postprandial Period; Potassium; Proteins; Proteinuria; Regression Analysis; Urinary Calculi; Urine

Topics: Aminoglycosides; Coloring Agents; False Positive Reactions; Humans; Molybdenum; Oxalates; Proteinuria; Pyrogallol

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

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

We determined total blood protein (TBP) and total urine protein (TUP) in healthy subjects and urolithiasis (UL) patients with renal calculi of different chemical composition: phosphate (CaP), oxalate (CaOx) and urate (HUr). We discussed the peculiarities of TBP and TUP distribution curves obtained and showed that the data on TBP and TUP do not make it possible to reliably single out patients with UL or determine the chemical composition of calculi in their kidneys. However, it was established that the comparison of TUP measurement results for UL patients using the Ponseau-S and sulfosalicylic acid methods makes it possible to reliably separate patients with Ca-containing calculi (CaP and CaOx) from those with HUr calculi. The explanation to this phenomenon using the data on the fractional composition of TUP and the organic matrix of those patients' calculi is given.

Topics: Azo Compounds; Benzenesulfonates; Blood Proteins; Coloring Agents; Humans; Kidney Calculi; Oxalates; Phosphates; Proteinuria; Salicylates; Solvents; Uric Acid

In preliminary studies, rats with chronic renal failure (CRF) demonstrated worsening renal function, as measured by urea clearance, when fed vitamin B-6-deficient diets. However, urea clearance is not a precise measure of glomerular filtration rate (GFR) and these studies did not indicate the mechanism for the reduced GFR. To measure renal function more precisely and to assess whether B-6 deficiency augments renal injury, we examined [14C]inulin clearance, urine oxalate excretion, and renal histopathology in rats with CRF pair fed to receive a pyridoxine-replete or -deficient diet for 3 or 6 wk. After 3 or 6 wk, pyridoxine-deficient rats had significantly lower [14C]inulin clearances and increased urine oxalate excretion. Histological evaluation indicated increased renal damage in kidneys from pyridoxine-deficient rats as compared with tissue from pyridoxine-replete rats. These findings suggest that in rats with CRF, vitamin B-6 deficiency reduces the GFR and increases renal scarring.

Topics: Animals; Aspartate Aminotransferases; Erythrocytes; Glomerular Filtration Rate; Inulin; Kidney; Male; Oxalates; Oxalic Acid; Proteinuria; Rats; Rats, Inbred Strains; Uremia; Vitamin B 6 Deficiency

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

The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons.

Topics: Calcium; Crystallization; Diphosphates; Diphosphonates; Humans; Hydrogen-Ion Concentration; Magnesium; Male; Molecular Weight; Organophosphonates; Oxalates; Phosphates; Proteinuria

Topics: Animals; Kidney Diseases; Liver Diseases; Oxalates; Proteinuria; Swine; Swine Diseases; Urea

Topics: Adult; Aged; Anesthesia, Inhalation; Blood Urea Nitrogen; Calcium; Creatinine; Female; Halothane; Humans; Kidney; Male; Methoxyflurane; Middle Aged; Osmolar Concentration; Oxalates; Phosphates; Proteinuria; Uric Acid

Topics: Adult; Creatinine; Humans; Hypertension; Male; Metabolism, Inborn Errors; Oxalates; Proteinuria

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Blood Pressure; Body Temperature; Body Weight; Creatinine; Diet; Erythrocytes; Glycosuria; Hematocrit; Humans; Ketones; Male; Oxalates; Proteinuria; Pyridoxine; Vitamin B Complex; Xanthurenates

Topics: Animals; Apatites; Calcium; Crystallization; Humans; Molecular Weight; Oxalates; Phosphates; Proteinuria; Pyelonephritis; Uric Acid; Urinary Calculi