Frequency of renal phosphate leak among patients with calcium nephrolithiasis.

BACKGROUND: Nephrolithiasis is a frequent disorder affecting 10 to 15% of the population in Europe and the United States. More than 80% of renal stones are made of calcium oxalate and calcium phosphate. The main identified risks for calcium renal stone formation are hypercalciuria and urinary saturation. A urine phosphate (Pi) loss is often associated with hypercalciuria; furthermore, hyperphosphaturia increases urinary saturation. METHODS: To determine whether urinary phosphate loss is associated with calcium urolithiasis, we measured renal Pi threshold (TmPi) in 207 stone formers with normal parathyroid hormone (PTH) serum concentration and in 105 control subjects. RESULTS: The TmPi followed a normal distribution in both groups. The mean TmPi was significantly lower in stone formers versus controls (0.72 +/- 0.13 vs. 0.87 +/- 0.18 mmol/L, P < 0.0001) because of a shift to the left of the TmPi distribution curve in the stone former population, with no evidence for bimodal distribution. Five percent of the controls had a TmPi <0.63 versus 19% of the stone formers. Daily urinary calcium excretion was significantly higher in stone formers than in controls. Calcium excretion was also significantly higher in stone formers with TmPi <0.63 mmol/L compared with those with TmPi > or =0.63. Serum PTH and ionized calcium concentrations were not different in stone formers and in control subjects, whatever the TmPi value. CONCLUSIONS:: A low TmPi is more frequently encountered in stone formers with a normal PTH concentration than in control subjects and is associated with a high urinary Ca excretion. The hypophosphatemia induced by a renal phosphate leak may predispose the subject to calcium stone formation by increasing the serum calcitriol level, calcium excretion, and urinary saturation.     

A study on the cause of urolithiasis of the upper urinary tract--clinical study of risk factors in the formation of stones in the upper urinary tract

Various risk factors and inhibitors of the stone formation of the upper urinary tract have been pointed out in urine. We examined the amount of daily excretion of several important risk factors (calcium, phosphorus, urate and oxalate) and inhibitors (magnesium and citrate) in the urine of 21 healthy males, 13 male single stone formeks and recurrent and/or multiple stone formers before and after taking the regular diet which contains 500 mg of calcium and 1,000 mg of phosphorus a day. The daily excretion of calcium, phosphorus and magnesium indicated no significant differences among the 3 groups. The excretion of oxalate in urine for 24 hours was significantly decreased in the stone formers after taking the regular diet. The urinary excretion of the urate per body surface area in the stone formers was significantly higher than that in the healthy control. The amount of the excretion of the citrate in urine in the recurrent and/or multiple stone formers was significantly lower than that in the other 2 groups. Many patients of the recurrent and/or multiple urinary stones had more than two abnormal values of above-mentioned risk factors and inhibitors. These results suggest that the causes of the formation of the upper urinary stone were not single but multiple and that the dietary advice to these patients was important against the recurrence of the urolithiasis.     

Clinical studies of the recurrence of urolithiasis (4). Crystal formation in urine and stone recurrence

Relationship between stone formation and crystal formation in urine was studied. Crystals in the sediments of early morning urine in 238 stone formers and the same numbers of non-stone formers were examined by light microscopy. Almost all crystals found in the early morning urine were composed of calcium oxalate both in stone formers and in non-stone formers. The frequency of calcium oxalate crystal formation was slightly higher in stone formers than in non-stone formers, but, no significant difference was noted. On the other hand, the urine containing calcium oxalate crystals of the stone formers had significantly lower specific gravity than that of the non-stone formers. Calcium oxalate crystals in the urine were formed significantly more frequently in the recurrent or bilateral male stone formers than in male unilateral stone formers without previous stone history. Frequency of calcium oxalate crystal formation was not influenced by urinary excretion of calcium, oxalate, uric acid, phosphate and magnesium. These finding led us to the conclusion that it was clinically useful to measure urinary specific gravity in which calcium oxalate crystals were formed in predicting the risk of stone formation.     

Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasties

Stones are a common complication of the storage of urine in intestinal reservoirs. Previous studies have identified predisposing physical characteristics in the reservoirs. Biochemical and dietary factors have been little investigated. Fifteen patients (6 males and 9 females) who had undergone various enterocystoplasty operations and who had subsequently formed either upper or lower urinary tract stones were investigated. The programme has been previously described and included stone, blood and urine analysis and dietary review. Comparison was made with 15 age- and sex-matched idiopathic stone formers with normal bladders. Stones were infective in origin in 86% of cases, and 14% were sterile. Metabolic screen showed that 80% of enterocystoplasty patients had risk factors for at least three different types of stone. All patients had raised pH (mean 6.93) and hypocitraturia. Five had a raised alkaline phosphatase. Raised serum and urinary calcium, hyperoxaluria and hyperuricosuria were found in 33% of patients. Five had a 24-h urine volume below 1.6 l/day. All patients had a high risk index (P _SF) for phosphatic stones and 12 also for calcium oxalate stones. Compared to age-and sex-matched idiopathic stone-formers, the urine had a higher pH, sodium and protein excretion and a lower calcium and citrate excretion. Although the patients were already selected as stone-formers, the data show that metabolic and dietary factors are present. They may be as important in the aetiology of the stones, as the already recognised factors of infection and poor reservoir drainage. Investigation should include such factors, the presence of which may be taken into account in a prophylactic regime.     

Uromucoid excretion in normal subjects,calcium stone formers and in patients with chronic renal failure

Summary Using an electroimmunoassay technique for uromucoid in urine, the excretion of this protein has been studied in normal subjects, calcium stone formers and in patients with chronic renal failure. In the normal subjects there was no significant difference in daily excretion between males and females, but a positive correlation with urine volume was demonstrated for this group. No significant difference in daily uromucoid excretion was found between normal and stone forming subjects. In the presence of chronic renal failure uromucoid excretion was found to be reduced and correlated with overall renal function as assessed by creatinine clearance.     

Stone composition and metabolic status

This paper aims to study the correlation between biochemical risk factors of the stone former and the type of oxalate stone formed, namely calcium oxalate monohydrate (COM) and calcium oxalate dehydrate (COD). A retrospective study of 487 patients who had been attending the urinary stone clinic, Trivandrum during 1998–2007 was conducted. The stones retrieved from them were subjected to chemical analysis and FTIR spectrographic analysis. They were categorized into COM, COD, mixed COM+COD and others. Of 142 pure calcium oxalate stone patients, 87 were predominantly COM stone formers and 55 COD stone formers. Their metabolic status of 24 h urine and serum was assessed. The values of urine calcium, phosphorus, uric acid, magnesium, creatinine, oxalate, citric acid, sodium and potassium, serum values of calcium, phosphorus, uric acid, magnesium and creatinine and calculated values of creatinine clearance, tubular reabsorption of phosphate, calcium magnesium ratio and calcium oxalate ratio were recorded. Comparison was made between the COM stone group and the COD stone group. Patients forming COM stones had significantly higher mean values for urine calcium (P < 0.05), oxalate (P < 0.01) and magnesium (P < 0.05) levels and significantly lower level of urine calcium–oxalate ratio (P < 0.01) and urine calcium–magnesium ratio (P < 0.01) compared to COD stone forming patients. All other values failed to show significant difference. Patients, with higher urine oxalate, formed COM stones. Those with low magnesium (which is an inhibitor) formed more of COD stones. Urine calcium was high in both groups without showing significant variation from the mean. In patients with high calcium–oxalate and calcium–magnesium ratios, there is higher chance of forming a COD stone than COM. Identification of the crystallization pattern of the calcium stone will help in selecting treatment modalities.     

Some laboratory findings in patients with urolithiasis

Twenty-four-hour urinary specimens from 22 patients with urolithiasis and urinary calcium excretion within the normal range were investigated. The urinary calcium excretion was significantly higher and the urinary osmolar excretion significantly lower in the stone formers than in the normals. Urinary calcium and osmolar excretion as well as urinary magnesium and osmolar excretion both in the patients and in the normals were found to be correlated. In the stone formers urine volume and urinary calcium, magnesium and osmolar excretion, as well as phosphate and osmolar excretion were correlated. These correlations have not been found in the normals. It is thought that in the stone formers the increased excretion of urine is secondary to increased urinary calcium excretion.     

Comparison of fibronectin content in urinary macromolecules between normal subjects and recurrent stone formers.

OBJECTIVES: Fibronectin (FN: 230 kD) is a multifunctional alpha(2)-glycoprotein distributed throughout the extracellular matrix and body fluids. Recent studies have shown that a variety of molecules, including FN, inhibit the endocytosis of calcium oxalate (CaOx) crystals in vitro. We recently reported that FN was oversecreted from the renal tubular cells as a result of the stimulation of CaOx crystals, and inhibited the aggregation of CaOx crystals and the adhesion of CaOx crystals to the renal tubular cells. In the present study, we investigated the difference of FN content in urinary macromolecules (UMMs) between normal subjects and recurrent stone formers. MATERIALS AND METHODS: Urinary parameters in relation to urolithiasis of normal subjects and recurrent stone formers were measured. Proteins in extracted UMMs from urine of normal subjects and recurrent stone formers were measured with a BioRad protein assay, GAGs in each UMMs with a modified DMB assay and the FN content with the ELISA method. RESULTS: In urinary parameters, citrate was significantly higher in urine from normal subjects (female) than normal subjects (male) or recurrent stone formers, and the other parameters showed no differences between each group. The protein concentrations in UMMs showed no differences between each group. Normal subjects (male and female) showed a significantly higher concentration of GAGs than recurrent stone formers (with and without silent stone). Compared with normal subjects and recurrent stone formers without silent stones, higher FN levels were found in recurrent stone formers with silent stones. Normal subjects showed a significantly higher concentration of FN than recurrent stone formers without silent stones. No difference in FN level was shown between normal subjects (male) and normal subjects (female). CONCLUSION: Recurrent stone formers with silent stones showed a significantly higher concentration of FN in UMMs than normal subjects. This finding suggests that FN might be oversecreted from the renal tubular cells as a result of the stimulation of CaOx stones in vivo. Recurrent stone formers without silent stones showed a significantly lower concentration of FN in UMMs than normal subjects. From this finding it is suggested that FN might play a role as a potent inhibitor of CaOx urolithiasis in a clinical setting.     

A family-based study of metabolic phenotypes in calcium urolithiasis

BACKGROUND: A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS: We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluations simultaneously, including 24-hour urine collection and oral calcium loading. Phenotypes were compared between affected and unaffected sibs from the same sibship. RESULTS: Eighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily urine calcium excretion was higher in affected compared with unaffected sibs (0.64 +/- 0.33 vs. 0.50 +/- 0.22 mmol Ca(2+)/mmol creatinine, respectively, P < 10(-5)). This corresponded to absolute values of 7.4 +/- 3.9 and 5.1 +/- 2.3 mmol Ca(2+)/day, respectively, for affected and unaffected males, and 5.4 +/- 2.6 and 4.2 +/- 1.9 mmol Ca(2+)/day, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium were only significant in the first two tertiles (with onset age of stone passage <35 years). The fasting urine Ca(2+)/creatinine ratio was significantly higher in stone formers compared with control sibs (0.46 +/- 0.27 vs. 0.40 +/- 0.27, P = 0.04), as was the postcalcium load Ca(2+)/creatinine ratio (0.57 +/- 0.46 vs. 0.43 +/- 0.41, respectively, P = 0.02). Body mass index was marginally significantly higher in stone forming sibs (P = 0.04). Other urine phenotypes, including oxalate, phosphate, magnesium, citrate, urate, sodium, ammonium, and volume, were not associated with stone passage. CONCLUSION: Increased urine calcium excretion is the only phenotype associated with a kidney stone formation in these French-Canadian families.     

Bone mass loss in calcium stone disease: focus on hypercalciuria and metabolic factors

BACKGROUND: Several authors have observed that idiopathic calcium stone formers show a bone mass reduction, which is more evident in those with idiopathic hypercalciuria. The aim of this work was the evaluation of osteopenia and osteoporosis rate in a group of idiopathic calcium stone formers. The influence of hypercalciuria, nutritional factors and anthropometric parameters on bone mass was evaluated in these patients as well. METHODS: We enrolled 196 idiopathic calcium stone formers; 102 males, and 94 females. All subjects underwent a metabolic study. BMC and BMD were evaluated as well as QUS. RESULTS: Males showed greater weight, height, BMI, densitometric values and plasma creatinine, uric acid, urea, sodium, magnesium, GFR and urinary osmolarity than females. Moreover males excreted more uric acid, urea, creatinine, sulphate, phosphate, oxalate and citrate than females. The prevalence of osteopenia and osteoporosis, according to T-score, was 54% and 14% respectively. Hypercalciuria was demonstrated in 21.7% of the patients. Hypercalciuric men showed a higher excretion of urea, phosphate, sulphate and magnesium. CONCLUSIONS: Our results confirm the importance of QUS in the evaluation of stone formers' bone mass. Anthropometric characteristics and dietary habits seem to play a role in bone loss. We did not demonstrate any influence of hypercalciuria on bone mass. Although the pathogenesis of bone loss in stone formers still remains unclear, it can be hypothesized that a slight degree of metabolic acidosis, probably of alimentary origin, may be involved in the reduction of bone mass.     

Urine risk factors in children with calcium kidney stones and their siblings

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.     

草酸钙结石患者尿中蛋白结合型γ-羧基谷氨酸的检测意义

目的　探讨含γ 羧基谷氨酸 (Gla)蛋白质及其Gla残基在尿石形成中的作用。　方法　采用过饱和结晶法从新鲜尿液中提取草酸钙晶体基质 ,高效液相色谱法 (HPLC)测定 2 5例草酸钙结石患者尿液和提取的晶体基质中蛋白结合型Gla含量。　结果　草酸钙结石患者尿蛋白结合型Gla浓度为 (1.32± 0 .2 4)nmol/ml,2 4h尿含量为 (2 .0 4± 0 .6 5 ) μmol,显著低于正常人 ;草酸钙结石患者尿液提取的晶体基质中蛋白结合型Gla含量亦显著低于正常人。　结论　草酸钙结石患者尿液中蛋白结合型Gla含量较少 ,尿液含Gla蛋白质的羧基化程度低下可能是结石形成的重要原因之一。     

Oxalate as a promoter in calcium oxalate nephrolithiasis]

Oxalate transports on membranes of red blood cell, intestinal epithelium and proximal tubule cell were reviewed, and the new findings about oxalate transport across these membranes are reported. Red blood cell oxalate influx rate in a group of recurrent calcium oxalate stone formers was significantly higher than that of a control group. In the red blood cells of mammals, the band 3 protein transports oxalate. Although abnormal influx rate of red blood cells might be recognized as an expression of somatic cell abnormality of oxalate transport in some recurrent stone formers, the band 3 protein is not related to oxalate transport in both kidney and intestine. The study using brush border membrane vesicles suggested the presence of Na-oxalate co-transport. In humans, sodium intake increased the oxalate/creatinine ratio of urine. This indicated that excessive sodium intake might be a risk factor of stone formation. Further study of oxalate transport of both kidney and intestine will be required to elucidate an etiology of calcium oxalate nephrolithiasis.     

Oxalate loading test for outpatients with calcium oxalate stones

A spinach loading experiment was performed on 9 normal subjects, 25 outpatients who were single calcium oxalate stone formers and 25 recurrent calcium oxalate stone formers. The experimental diet contained 445 mg of total oxalate, 163 mg of soluble oxalate and 115 mg of calcium. Urinary oxalate excretion was observed 2 hrs before and 6 hrs after the experimental diet was consumed. There was no significant difference in urinary oxalate excretion in preloading urine of normal subjects and stone formers. However, urinary oxalate excretion in postloading urine was significantly elevated in stone formers. This loading test is recommended as a simple and valuable screening method of hyperabsorption of oxalate on outpatients with calcium oxalate stones.     

Rethinking the role of urinary magnesium in calcium urolithiasis

BACKGROUND AND PURPOSE: The role of magnesium in urinary stone formation remains undefined. In vivo, magnesium inhibits stone formation in hyperoxaluric rats, and small clinical studies suggest a protective effect of magnesium supplementation in calcium oxalate stone formers. We performed a retrospective review of more than 7,000 stone patients to see if there is a relation between urinary magnesium and other stone risk variable constituents. MATERIALS AND METHODS: A national database of stone formers categorized by residential ZIP code was queried, and, using strict inclusion criteria, 2,147 patients having pure calcium oxalate stones were identified. There were 1,912 (89%) eumagnesuric (43-246 mg/24 hours) and 235 (11%) hypomagnesuric (<43 mg/24 hours) patients. RESULTS: Patients with decreased urinary magnesium excretion had significantly less daily urine excretion of citrate, calcium, oxalate, uric acid, and sodium than the eumagnesuric group (p < 0.0001). Stone recurrence was slightly more common in the hypomagnesuric group, although the difference was not statistically significant. The percentage of patients voiding <1 L of urine per day was significantly higher in the hypomagnesuric group. In the eumagnesuric group, males outnumbered females 2:1, whereas hypomagnesuric patients showed a female predominance of 1.4:1. CONCLUSION: The beneficial effects of urinary magnesium on stone formation may be less than previously reported. The role of oral magnesium supplementation and the subsequent increase in urinary magnesium in calcium urinary stone formation remains unknown. Our data suggest that its effect on or interaction with citrate may be influential on urinary citrate concentrations. If magnesium has a protective effect, it may work through pathways that enhance citrate excretion.     

Involvement of low-calcium diet in the reduced bone mineral content of idiopathic renal stone formers

Summary The possibility that low-calcium intake in renal stone formers could lead to reduced bone mineral content was investigated in 123 male patients with idiopathic urolithiasis. Radius bone mineral content, (BMC) was measured by single photon absorptiometry. Two groups of patients were analyzed: group 1 (n=63) maintained on a free diet; group 2 (n=60) maintained on a low-calcium diet (350 mg/day ±20 SEM) for 3.9 years ±0.6 SEM. The two groups of patients were investigated after a standard reduction of calcium intake for at least 1 week. The urinary excretion of calcium and of hydroxyproline, and the serum alkaline phosphatase activity were higher in both groups than in normal subjects submitted to the same low-calcium diet. Both groups of stone formers showed lowered radius BMC values at 3 cm (distal) and 8 cm (proximal) above the styloid process, but distal BMC was significantly lower in group 2 than in group 1. The results suggest that low-calcium intake could worsen the already decreased BMC of idiopathic renal stone formers.     

Urinary stone risk factors in the siblings of patients with calcium renal stones

PURPOSE: We determined which, if any, urinary stone risk factors accurately discriminate stone forming and nonstone forming siblings of patients with calcium renal stones. MATERIALS AND METHODS: A total of 252 siblings of stone formers provided 2, 24-hour urine samples, which were sent overnight and analyzed at a central laboratory. Standard stone risk factors were measured and the supersaturation of calcium oxalate, calcium phosphate and uric acid was calculated. RESULTS: Discriminant functions were derived for each gender by multivariate analysis. In stone forming sisters higher urinary calcium and pH discriminated with a success rate of 70%. In stone forming brothers higher urinary calcium, lower urinary potassium and older age discriminated with a success rate of 79%. CONCLUSIONS: Select urinary measurements as well as age classify siblings into those with and without stones with fair accuracy. Calcium excretion and urinary pH in females, and calcium excretion, urinary potassium and age in males are feasible identifiers of stone forming siblings. To determine whether these measurements can be used to predict new stone onset may require years of observation of our current cohort.     

Hyperoxaluria in idiopathic calcium nephrolithiasis--what are the limits?

OBJECTIVE: The object of this study was to investigate the role for measurement of 24-h renal oxalate excretion in the evaluation of idiopathic calcium stone formers. MATERIALS AND METHODS: Renal excretion rates of oxalate and creatinine were measured in 24-h urines in 46 consecutive male recurrent idiopathic calcium stone formers and 61 healthy males. Furthermore, day-to-day variation in renal oxalate excretion in 10 male recurrent stone formers and 10 healthy males were evaluated by measuring 24-h oxalate excretion on 5 different days in each individual. Concentrations of oxalate in urine were measured using an enzymatic method without ascorbate interference. RESULTS: The cumulative frequency distribution curves of 24-h renal oxalate excretion rates of stone formers and controls were congruent, and there were no statistically significant differences in oxalate excretion rates between stone formers and controls. Mean 24-h oxalate excretion (95%-confidence intervals) was 0.22 (0.18-0.25) mmol and 0.21 (0.18-0.24) mmol in stone formers and controls, respectively (p = 0.9). The day-to-day variation study did not reveal any differences in renal oxalate excretion pattern between stone formers and controls, and the presence of intermittent hyperoxaluria could not be confirmed. The oxalate excretion rates were generally low. CONCLUSION: In our region, there appear to be no differences in 24-h renal excretion rates of oxalate between male recurrent idiopathic calcium stone formers and healthy males, and the syndrome of mild hyperoxaluric calcium nephrolithiasis could not be identified in our population of idiopathic stone formers. Hence, a limit of abnormal oxalate excretion that distinguishes an idiopathic stone former from a non-stone former could not be defined in our population. Therefore, the value of routine measurement of urinary oxalate in idiopathic urolithiasis is difficult to accept, and cannot be recommended.     

Causes and consequences of kidney loss in patients with nephrolithiasis

BACKGROUND: It is unknown whether stone formers may safely donate a kidney. Nephrectomy could accelerate stone formation, or loss of filtration with age. We contrast, here, the course of stone patients with two versus one kidney. METHODS: One hundred fifteen patients with a single functioning kidney were compared with 3151 patients with two kidneys. Cause of kidney loss was determined, along with stone types, rates of stone formation, urine stone risk factors, and creatinine clearance. RESULTS: Women were 49.6% of the patients with kidney loss, compared to 33.6% of ordinary stone formers. Obstruction, stone burden, and infection were the most common reasons for kidney loss. We found an increased number of struvite and calcium phosphate stones among single kidney patients. Before and during treatment, single kidney patients had fewer stones than ordinary stone formers. Creatinine clearance was lower in the single kidney patients; rate of loss of kidney function with age was higher among single kidney males versus two kidney males if all patients are considered. Among males >age 45 years, the difference disappears. Females with one and two kidneys lost function with age at equivalent rates. Compared with nonstone formers, male stone formers lose kidney function with age at an accelerated rate. CONCLUSION: Nephrectomy does not worsen stone disease. It may increase loss of renal function among younger males. The pattern of renal function loss with age differs between stone formers and nonstone formers.     

The urinary response to an oral oxalate load in recurrent calcium stone formers

PURPOSE: Dietary oxalate may contribute up to 50% to 80% of the oxalate excreted in urine. We studied the urinary response to an oral oxalate load in male and female idiopathic recurrent calcium oxalate stone formers with and without mild hyperoxaluria to evaluate the potential pathophysiological significance of dietary oxalate. MATERIALS AND METHODS: A total of 60 recurrent calcium stone formers underwent an oral oxalate load test. Urine samples were obtained after an overnight fast. Each patient then received an oral oxalate load (5 mM. sodium oxalate dissolved in 250 ml. distilled water) and 3, 2-hour urine samples were obtained 2, 4 and 6 hours after the oxalate load. We compared the response to the oxalate load in patients with and without mild hyperoxaluria, and in male and female patients without hyperoxaluria. RESULTS: The peak urinary response occurred 4 hours after the oral oxalate load in all patients. Those with mild hyperoxaluria had a mean fasting urinary oxalate-to-creatinine ratio +/- SE of 0.027 +/- 0.003 and a mean peak urinary oxalate-to-creatinine ratio of 0.071 +/- 0.006. In comparison, patients with normal oxalate excretion had a fasting and peak urinary oxalate-to-creatinine ratio of 0.018 +/- 0.001 and 0.056 +/- 0.004, respectively (p <0.05). The mean 6-hour increment for urinary oxalate excretion after the oxalate load for patients with hyperoxaluria versus those with normal urinary oxalate excretion was 17.2 +/- 1.9 versus 12.1 +/- 0.98 mg. (p <0.05). In the subset of patients with normal urinary oxalate excretion mean 6-hour cumulative urinary oxalate excretion was 16.8 +/- 1.3 and 13.3 +/- 1.4 mg. in males and females, respectively (p not significant). CONCLUSIONS: Recurrent calcium stone formers with mild hyperoxaluria have higher fasting urinary oxalate and an exaggerated urinary response to an oral oxalate load compared with recurrent calcium stone formers with normal urinary oxalate excretion. Men and women stone formers without hyperoxaluria excrete similar fractions of an oral oxalate load. Increased gastrointestinal absorption and renal excretion of dietary oxalate may be a significant pathophysiological mechanism of stone formation in patients with mild hyperoxaluria.