Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers.

Background: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP. Methods: To test this idea, we analyzed two large but separate sets of 24-h urine samples and paired serums of 2700 SFs from the University of Chicago and 11 073 SFs from Litholink, a national laboratory. Patients were divided into quintiles based on serum phosphate. Results: Males were more common in the lowest phosphate tiles in both datasets. Phosphate excretion did not vary across the quintiles, excluding diet as a cause of HYP. Tubule maximum (Tm) phosphate per unit glomerular filtration rate decreased and fractional excretion increased with decreasing phosphate quintiles, indicating reduced tubule phosphate reabsorption was responsible for HYP. Urine pH and serum chloride increased with decreasing serum phosphate, suggesting a coordinate change in NHE3 activity. Serum uric acid and Tm uric acid decreased significantly with decreasing serum phosphate, while uric acid excretion did not vary. Conclusion. HYP in SFs results from decreased tubule phosphate reabsorption and, being associated with related changes in other proximal tubule transporters, may arise from alterations in or signaling to PDZ-containing proteins.

Evidence for durable kidney stone prevention over several decades.

OBJECTIVE: To analyse three outcomes of stone prevention strategies in one clinic devoted to that activity since 1969, i.e. stone recurrence rates, stone-related procedures and 24-h urinary stone risk factor, to assess whether such treatment can be maintained over long periods. PATIENTS AND METHODS: We selected 2509 patients with at least one laboratory follow-up after initial clinical and laboratory evaluation. We divided them into five time cohorts of 5, 10, 15, 20 and >20 years of follow-up. Rates of new stones and stone-related procedures, and 24-h urinary stone risk factors were compared between the cohorts using analysis of variance and general linear modelling. RESULTS: Stone rates and rates of stone-related procedures declined in all five cohorts, as did 24-h urinary stone risk indices. We found no diminution of treatment effects for any of these three over time. CONCLUSION: Those patients who remained under active care had significant reductions in stone recurrence and rates of stone-related urological procedures for up to >20 years. However, only a small fraction of patients who entered the clinic remained for such long periods. Urine testing substantiates impressive and sustained reductions in supersaturation, the principle driving force for stone formation. Overall, for those patients willing to remain in continuous treatment for periods of up to three decades, medical stone prevention appears to be effective in maintaining low recurrence and procedure rates.

Clinical and laboratory characteristics of calcium stone-formers with and without primary hyperparathyroidism.

OBJECTIVE: To compare the clinical presentation, laboratory features and outcome of treatment in stone formers (SF) with primary hyperparathyroidism (HPT) to those without systemic disease. PATIENTS, SUBJECTS AND METHODS: We compared 105 (54 female) stone-formers (SF) with primary hyperparathyroidism (HPT) to 2416 (835 female) common SF with no systemic disease, and 260 normal subjects (NS, 106 female) using pre-treatment and treatment data from our kidney-stone programme. All were assessed before treatment, with three 24-h urine samples, for stone risk factors, each with a corresponding fasting blood sample. Records were reviewed for stone rates and urological stone-related procedures. RESULTS: The hypercalcaemia of HPT was modest, but hypercalciuria was far more marked than in SF because the fractional calcium excretion of HPT exceeded that of SF. Surgical cure of HPT did not completely eradicate either hypercalciuria or hypophosphataemia, suggesting that these patients have some additional mineral disorder. Serum calcium and phosphate, and fractional excretion of calcium, combined into a discriminant function provided the best separation between HPT and SF. However, we present 49 patients for whom the diagnosis (HPT vs SF) has never been resolved, despite years of observation and successful reduction of stone recurrence. Stones in HPT have slightly more phosphate than SF but the difference is not large enough to be of clinical interest. The stone frequency in HPT is about that for SF, and treatment reduces stones in HPT and SF by about the same amount, 10 times. CONCLUSION: No study to date has compared HPT with SF and NS, as done here. SF with even slight hypercalcaemia and brisk hypercalciuria probably have this curable disease, and after cure clinicians must be wary of residual hypercalciuria that requires medical treatment. Some patients will never be fully diagnosed and remain, like ours, an enigma, albeit responsive to usual medical treatments. Although stones are modestly enriched with phosphate, most are mainly calcium oxalate, so the stone analysis is not clinically a guide to diagnosis.

Urine pH in renal calcium stone formers who do and do not increase stone phosphate content with time.

BACKGROUND: Calcium phosphate (CaP) renal stones appear to be increasing in prevalence, and are caused by high urine CaP supersaturation, which arises from genetic hypercalciuria and high urine pH. Renal damage from stones or procedures, or treatments for stone could raise urine pH; alternatively pH may be intrinsically high in some people who are thereby predisposed to CaP stones. METHODS: To distinguish these alternatives we sequenced changes in urine pH and stone CaP content asking which occurs first in patients whose stones showed progressive increase in CaP over time. From 4767 patients we found 62 in whom we could document transformation from calcium oxalate (CaOx) to CaP stones, and 134 CaOx controls who did not transform. Laboratory and clinical finding were contrasted between these groups. RESULTS: Even when patients were forming relatively pure CaOx stones, those destined to increase stone CaP had higher urine pH than controls who never did so. Their higher pH was present before and during treatments to prevent new stone formation. Shock wave lithotripsy was strongly associated with increasing stone CaP but urine pH bore no relationship to number of procedures. CONCLUSION: We conclude that high pH may not be acquired as a result of stones or their treatments but may precede transformation from CaOx to CaP stones and arise from diet or possibly heredity.

Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle.

Our purpose here is to test the hypothesis that Randall's plaques, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative biopsies of plaques in kidneys of idiopathic-calcium-stone formers and patients with stones due to obesity-related bypass procedures and obtained papillary specimens from non-stone formers after nephrectomy. Plaque originates in the basement membranes of the thin loops of Henle and spreads from there through the interstitium to beneath the urothelium. Patients who have undergone bypass surgery do not produce such plaque but instead form intratubular hydroxyapatite crystals in collecting ducts. Non-stone formers also do not form plaque. Plaque is specific to certain kinds of stone-forming patients and is initiated specifically in thin-limb basement membranes by mechanisms that remain to be elucidated.

Peripheral blood monocyte vitamin D receptor levels are elevated in patients with idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis. Increased intestinal calcium absorption and bone resorption and decreased tubule calcium reabsorption may be caused by elevated serum 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] in some patients but not in those with normal serum 1,25(OH)(2)D(3) levels. Because 1,25(OH)(2)D(3) exerts its biological actions through binding to the cellular vitamin D receptor (VDR), the present study was undertaken to test the hypothesis that VDR levels are elevated in IH patients. Ten male IH calcium oxalate stone-formers were paired with controls matched in age within 5 yr and lacking a history of stones or family history of stones. Blood was obtained for serum, peripheral blood monocytes (PBMs) were separated from lymphocytes and other mononuclear cells, and PBM VDR content was measured by Western blotting. The PBM VDR level was 2-fold greater in IH men at 49 +/- 21 vs. 20 +/- 15 fmol/mg protein, mean +/- sd; P < 0.008. Serum 1,25(OH)(2)D(3) levels were not higher than controls (48 +/- 14 vs. 39 +/- 11 pg/ml; P < 0.068). In conclusion, PBM VDR levels are elevated in IH calcium oxalate stone-formers. The elevation could not be ascribed to increased serum 1,25(OH)(2)D(3) levels. These results suggest that the molecular basis for IH involves a pathological elevation of tissue VDR level, which may elevate intestinal calcium absorption and bone resorption and decrease renal tubule calcium reabsorption. The mechanism for increased VDR in IH patients with normal serum 1,25(OH)(2)D(3) levels is unknown.

Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients.

A main mechanism of idiopathic hypercalciuria (IH) in calcium stone-forming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1-h measurements of the clearances of sodium, calcium, and endogenous lithium during a three-meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normal subjects. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ, but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque.

Evidence that postprandial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis.

Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The increased urinary calcium arises from increased intestinal absorption of calcium, but it is unclear whether increased filtered load or decreased renal tubular reabsorption of calcium is the main mechanism for the increased renal excretion. To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1 day. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, and calories. Fasting and fed, ultrafiltrable calcium levels, and filtered load of calcium did not differ between N and IHSF. Urine calcium rose with meals, and fractional reabsorption fell in all subjects, but the change was significantly higher in IHSF. The changes in calcium excretion were independent of sodium excretion. Serum parathyroid hormone levels did not differ between N and IHSF, and they could not account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and phosphorus levels in IHSF were below N throughout the day, and tubule phosphate reabsorption was lower in IHSF than N after meals. The primary mechanism by which kidneys ferry absorbed calcium into the urine after meals is via reduced tubule calcium reabsorption, and IHSF differ from N in the magnitude of the response. Parathyroid hormone is not likely to be a sufficient explanation for this difference.

Renal function in patients with nephrolithiasis.

PURPOSE: We describe kidney function, as measured by creatinine clearance in stone formers, and classified by type of stone formed and systemic etiologies of stone formation. MATERIALS AND METHODS: The mean of 3 pretreatment 24-hour creatinine clearance measurements in each of 1,856 stone formers and creatinine clearance in 153 normal individuals were used. Clearance was adjusted for patient sex, age and body weight using general linear modeling. RESULTS: As a group, all stone formers had decreased clearance adjusted for age, sex and body weight compared to that in normal individuals. Although clearance was particularly low in cystine and struvite stone formers, they were below normal in even common CaOx stone formers. CONCLUSIONS: As a rule, patients with kidney stones do not have normal kidney function. In clinical management all efforts must be made to minimize renal injury, balancing the risks of obstruction from stones against those of urological procedures.

Reduced renal function and benefits of treatment in cystinuria vs other forms of nephrolithiasis.

UNLABELLED: A significant study from the USA compares cystine stone formers and routine stone formers; the former group had a higher requirement for therapeutic procedures, but this was less if they took chelating agents, although remaining higher than in the latter group. Other interesting findings are also presented. OBJECTIVE: First, to compare two types of stone formers (SF), those with cystinuria and those without, for effects of treatments for stones, as cystinuria leads to recurrent stones that are difficult to fragment with shock-wave lithotripsy, and there is disagreement about the efficacy of current treatments. Second, to compare these two groups with respect to blood pressure (BP) and renal function, as cystine stones may be associated with more morbidity than are routine stones. PATIENTS AND METHODS: Fifty-two cystinuric patients (cystine SF) entering our programme since 1970 were compared with 3215 SF without cystinuria (routine SF), of whom 114 had a single functioning kidney (routine SF + nephrectomy). All patients had three 24-h urine and blood samples taken to determine the risk of stones before their first clinic visit; these studies were repeated after therapy was initiated, and at regular intervals to monitor therapy. Cystine was measured in the urine samples of the cystine SF. All stone-related procedures were recorded, and BP measured at clinic visits. Creatinine clearances (CCr) were calculated from each set of serum and urine values. Cystine supersaturation (SS) was directly measured in 16 urine samples collected before treatment and 13 afterward. RESULTS: Patients were treated with increased fluid intake, potassium alkali and chelating agents such as alpha-mercapto-propionyl-glycine, as needed. The mean (sd) CCr, corrected for age and gender, was significantly lower at entry in cystine SF than in routine SF, at 91 (6) vs 160 (1) L/day, respectively (P < 0.001), and remained so at the last CCr. Neither systolic nor diastolic BP, similarly corrected, differed between the groups, but cystine SF had significantly more procedures, corrected for time at risk, before treatment than did routine SF, at 4.0 (0.4) vs 1.86 (0.06), respectively (P < 0.001); time-adjusted procedures decreased significantly in both groups during treatment, but remained higher in cystine SF, at 0.88 (0.14) vs 0.23 (0.02), respectively, (P < 0.001). Urine volume and pH were significantly higher in cystine SF than in routine SF, both before and during treatment. Cystine SS decreased during treatment, consistent with the increase in urine volume and decline in procedure rates during treatment. CONCLUSION: Cystine SF have significantly higher procedure rates than routine SF, but procedure rates decline during therapy, although they remain higher than in routine SF. The lower CCr in cystinurics suggests that treatment to prevent stone recurrence and the need for procedures is particularly important, and emphasizes the need for a close follow-up. Use of cystine SS measurements may allow closer monitoring of the effect of treatment on the risk of stone recurrence.

Crystal-associated nephropathy in patients with brushite nephrolithiasis.

BACKGROUND: We have biopsied the renal cortex and papillae of patients who form brushite renal stones asking if this unusual stone type is associated with specific tissue changes. We contrasted these with biopsies of 15 calcium oxalate stone formers, three stone formers with intestinal bypass, and four normal subjects. METHODS: We studied all ten brushite stone formers treated with percutaneous nephrolithotomy (PNL) during the past 3 years using digital video imaging of renal papillae, and obtained cortical and papillary biopsies. Biopsies were analyzed by light and electron microscopy, microinfrared spectroscopy, and electron diffraction. RESULTS: Apatite crystals plugged scattered terminal collecting ducts whose cells were injured or dead, and surrounding interstitium inflamed and fibrotic. White papillary deposits of interstitial apatite particles, so called Randall's plaque, were also present. Glomerular changes and cortical tubular atrophy and interstitial fibrosis were moderate to severe. CONCLUSION: Brushite stone formers combine the interstitial plaque of calcium oxalate stone formers with the collecting duct apatite plugs found in stone formers with intestinal bypass. Collecting duct injury and interstitial fibrosis are severe. Prominent cortical fibrosis, tubule atrophy, and glomerular pathology seem secondary to the collecting duct plugging. We believe crystallization obstructs and destroys terminal collecting duct segments thereby damaging nephrons, perhaps via intranephronal obstruction, and producing a hitherto unrecognized renal disease.

Nephrolithiasis and nephrocalcinosis in rats with small bowel resection.

Intestinal resection (IR) may lead to hyperoxaluria and nephrolithiasis. A rat model of IR was developed, in which kidney stones form. We describe the urine chemistries and histopathologic features. Rats underwent resection of 40-45 cm of distal ileum (n=16) or sham resection (SR) (n=8), and were then fed a 1% Na oxalate, 0.02% Ca diet. After 1 week on the diet, 24 h urine samples were obtained for stone chemistries. At 4-7 months after surgery, kidneys were examined grossly and by light microscopy. The extent and location of crystallization was assessed by polarized light. Histochemistry and infrared spectroscopy were used to determine crystal composition. IR rats had higher urine oxalate excretion (P<0.01) and concentration (P<0.001) than SR rats, and lower urine citrate excretion; only IR rats formed kidney stones (12/15 surviving rats). Tissue calcification was found only in kidneys from IR rats, located in the cortex (83% of kidneys), medulla (73%) and papillary tip (47%). Crystals, composed of CaOx, apatite, and calcium carbonate, filled collecting duct lumens, and were associated with tubular obstruction, and interstitial inflammation. Crystals in the papillary interstitium incited inflammation with tubular destruction and development of progressive papillary erosion. This new rat model of nephrolithiasis and nephrocalcinosis resembles the pattern of urinary abnormalities and tissue calcification that may be seen in humans with small bowel resection. The model allows further studies of the mechanisms of renal crystal formation, and possible therapeutic interventions.

Stone formation is proportional to papillary surface coverage by Randall's plaque.

PURPOSE: Randall's plaques are common in calcium oxalate (CaOx) stone formers (SF). Plaque coverage correlates directly with urine calcium excretion and inversely with urine volume. We hypothesize that plaque coverage should increase proportionally with increasing stone number. We measured plaque areas in idiopathic CaOx stone formers and nonstone formers (NSF), and identified significant relationships with quantified stone histories. MATERIALS AND METHODS: A total of 13 SFs and 4 control NSFs underwent nephroscopic papillary mapping with representative still images and MPEG (Moving Pictures Experts Group) movies used to identify plaque and papillary borders. Stone histories were obtained through patient interviews, and from medical records and radiographs. The relationship of plaque coverage to clinical stone events was assessed by general multivariate linear modeling. Log transformation normalized the distribution of percent plaque coverage and stone number. RESULTS: Plaque surface area in SFs differed significantly from that in NSFs (p <0.0001). The duration of stone disease and the log transformed percent plaque coverage correlated significantly with the number of stones (0.677 and 0.620, p = 0.003 and 0.008, respectively). On multivariate analysis and correcting for the duration of stone disease total percent plaque coverage correlated significantly with the number of stones (R = 0.496, p = 0.05). Disease duration and plaque coverage did not correlate significantly (p = 0.257). CONCLUSIONS: Percent plaque coverage directly correlates with the number of stones formed even when corrected for the duration of stone disease. However, plaque coverage does not correlate with the duration of stone disease. These results support the hypothesis that the pathogenesis of CaOx stones begins with Randall's plaques.

Thiazide does not affect urine oxalate excretion.

PURPOSE: We assessed the effects of thiazide treatment on urine oxalate excretion in patients with kidney stones. MATERIALS AND METHODS: Of 537 patients (231 women), 209 (81 women) received thiazide for stone prevention. Urine oxalate was measured in 3, 24-hour urines before treatment, and in 1, 24-hour urine after 6 to 12 weeks of treatment. This was an observational cohort and treatment was not randomized. RESULTS: Urine oxalate increased in general. There was no difference in increase with or without thiazide, whether one considered simple t test comparisons or used ANOVA with pretreatment oxalate excretion as a covariate. CONCLUSIONS: Thiazide administration exerts no measurable effect on urine oxalate excretion that can be detected in clinical practice.

Gender differences in seasonal variation of urine stone risk factors.

PURPOSE: We determined whether men and women differ in urine stone risk factors during the 4 seasons of the year. MATERIALS AND METHODS: Measurements from 28,498, 24-hour urines from stone forming patients prior to treatment were analyzed to determine whether monthly variation was significant and whether the sexes differed using ANOVA. Locations of supersaturation maxima were determined. RESULTS: The 2 sexes showed modest sodium depletion in summer with a corresponding decrease in urine calcium but men showed a remarkable decrease in urine volume, causing high calcium oxalate supersaturation. Women had maximum calcium oxalate supersaturation in early winter because of decreasing urine volume and increasing urine calcium excretion. Urine pH was reduced in the 2 sexes during summer but the decrease was far more marked in men, who had a uric acid supersaturation spike. PURPOSE: Overall the sexes differ markedly in the timing of stone risk. Men show a dual summer calcium oxalate and uric acid high risk, while women show a high early winter calcium oxalate high risk.

Changes in urine volume accomplished by physicians treating nephrolithiasis.

PURPOSE: We quantified the changes in urine volume and sodium accomplished in various practice settings and the consequent effects on calcium oxalate supersaturation. MATERIALS AND METHODS: We determined comprehensive urine stone risk factors in 2,877 patients treated in 14 practices, including a university referral center and private sector practices. Changes in urine volume and stone risk factors were measured. RESULTS: In a wide range of practice settings the volume increase was about 0.3 l. daily. Urine sodium excretion increased with volume for unexplained reasons, as did urine calcium excretion. As expected, thiazide lowered calcium excretion but the effect progressively decreased as urine volume increased. Therefore, urine calcium and calcium oxalate supersaturation changes were the result of opposing forces. The net effect was a decrease partly offset by sodium and calcium excretion increases. CONCLUSIONS: Urine volume increments are modest in practice and they are modestly offset by increases in urine sodium due to increased sodium intake. Clinicians should strive for higher volume increases than are currently achieved and be vigilant concerning what seems to be a strong tendency toward a higher sodium intake with more fluids.

A single 24-hour urine collection is inadequate for the medical evaluation of nephrolithiasis.

PURPOSE: We determined the adequacy of a single 24-hour urine sample for evaluating patients for medical renal stone prevention. MATERIALS AND METHODS: A total of 459 patients from a private urology practice specializing in the treatment of urolithiasis and 683 from a university stone research clinic provided 2 and 3, 24-hour urine samples, respectively. We used samples 1 and 2 from private practice patients, and 1 and 3 from university clinic patients for analysis, and compared each to the others by correlation coefficients and calculation of the mean difference plus or minus standard deviation (SD) of the difference. Urine risk factors were measured by standard methods. RESULTS: Although the correlation of urine values 1 and 2 was excellent for all stone risk factors, SD values for the differences were large enough that within 1 SD on either side of 0, which included 68.8% of cases, by chance urine 1 would depart from urine 2 by clinically important amounts. These departures would be more than sufficient to misdiagnose common metabolic disorders. CONCLUSIONS: A single 24-hour sample is not sufficient for evaluating patients before metabolic treatment for stone prevention because misdiagnosis is common, leading to inappropriate treatment.

Reduced crystallization inhibition by urine from women with nephrolithiasis.

BACKGROUND: Human urine is known to inhibit growth, aggregation, nucleation, and cell adhesion of calcium oxalate monohydrate (COM) crystals, the main solid phase of human kidney stones. This study tested the hypothesis that low levels of inhibition are present in women with calcium oxalate stones and, therefore, could promote stone production. METHODS: In 17 stone-forming women and 17 normal women matched in age within five years, inhibition by dialyzed urine proteins of COM growth and aggregation was examined, as well as whole urine upper limits of metastability (ULM) for COM and calcium phosphate (CaP) in relation to the corresponding supersaturation (SS). RESULTS: Compared to normals, patient urine showed a reduced ULM in relation to SS. In contrast to men, there was no difference in growth inhibition. CONCLUSIONS: Reduced CaP and CaOx ULM values in relation to SS are a characteristic of female stone formers. This defect could promote stones by facilitating crystal nucleation. Abnormal inhibition may well be a very important cause of human nephrolithiasis.

Outcome of metabolic evaluation and medical treatment for calcium nephrolithiasis in a private urological practice.

PURPOSE: We determine if medications that have been proven effective for kidney stone prevention in prospective controlled trials can reduce kidney stone recurrence in a private practice of urology better than life-style advice, including hydration. MATERIALS AND METHODS: Between July 1, 1995 and December 31, 1996, 203 patients with stones received care from 1 private practice. Physicians chose to evaluate these patients metabolically based on clinical judgement. Thiazide, potassium citrate and allopurinol are recognized in this study as active treatments, and drug treatment intervals were calculated. Relapse and recurrent stones were counted as those stones manifesting after the initial index event. A stone was called a relapse stone if its date was included in the active treatment interval. RESULTS: The association between use of active therapy and ordering of metabolic evaluation was highly significant. Using survival tables, we separately considered all patients and only those who had formed more than 1 stone. For both populations active treatment reduced stone recurrence significantly more than diet advice and hydration. CONCLUSIONS: Medications validated in trials and guided by metabolic evaluation lower stone recurrence when used in a private practice setting as they do in trials.

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.