Heavy elements in urinary stones.

The presence and role of heavy metals in urinary stones is debated. We investigated the distribution of trace heavy metals in 78 calculi of well-defined composition by means of microfluorescence X analysis using synchrotron radiation. Seven elements were identified, the most abundant being Zn and Sr which together accounted for 91% of the heavy metal content of stones. The other heavy metals were Fe, Cu, Rb, Pb and Se. Zn and Sr were virtually confined to calcium-containing stones, whereas only trace amounts were found in uric acid or cystine stones. Among calcium stones, Zn and Sr were more abundant in calcium phosphate than in calcium oxalate stones and, in the latter, in weddellite than in whewellite stones. Fe, Cu and Rb were much less abundant and also found mainly in calcium stones. Pb was significantly less abundant than in previous studies, thus suggesting a rarefaction of Pb in the environment, and appreciable amounts of Se were found only in cystine stones. In conclusion, the preponderance of Zn and Sr, both bivalent ions, in calcium-containing stones suggests a substitution process of calcium by metal ions with similar charge and radius rather than a contribution of the metals to stone formation. Further studies are needed to examine the relationships between urine concentration in calcium or other solutes and the amount of Zn and Sr in calcium stones.

[Clinical value of crystalluria study]. / Intérêt clinique de l'étude de la cristallurie.

Crystalluria is a marker of urine supersaturation present in both normal and pathological conditions. Indeed, nature and characteristics of the spontaneous crystalluria are of clinical interest for detecting and following biological disorders involved in renal diseases. Method. Crystalluria examination should preferably be performed on first morning urine or fresh fasting voiding samples by polarised microscopy in a Malassez cell. Urine samples must be stored at 37 degrees C or at room temperature and examined within two hours following voiding. Results and discussion. Crystalluria should be interpreted according to various criteria: 1) chemical nature of crystals for abnormal crystals such as struvite, ammonium urate, cystine, dihydroxyadenine, xanthine or drugs; 2) crystalline phase of common chemical species as calcium oxalates, calcium phosphates and uric acids; 3) crystal morphology (calcium oxalates); 4) crystal size (calcium oxalates); 5) crystal abundance (calcium oxalates, calcium phosphates, uric acids, cystine); 6) crystal aggregation (calcium oxalates); 7) frequency of crystalluria assessed on serial first morning urine samples, a very useful tool for long-term surveillance of patients. Within calcium oxalate crystalluria, presence of whewellite is a marker of elevated oxalate concentration (urine oxalate > 0.3 mmol/L); a crystal number > 200/mm 3 is highly suggestive of heavy hyperoxaluria of genetic or absorptive origin. Predominant weddellite crystalluria is most often indicative of an excessive urine calcium concentration (> 3.8 mmol/L); a dodecahedric aspect of the crystals is a marker for heavy hypercalciuria (> 6 mmol/L) while an increased crystal size (>or= 35 microm) is indicative of simultaneous hypercalciuria and hyperoxaluria. Calculation of the global crystal volume, especially when applied to calcium oxalates or cystine, is a clinically useful tool for the monitoring of patients suffering from primary hyperoxaluria or cystinuria. Lastly, presence of crystalluria in more than 50% of serial first voided morning urine samples is in our experience the most reliable biological marker for detecting the risk of stone recurrence in lithiasic patients. Conclusion. Crystalluria examination is an essential laboratory test for detecting and following pathological conditions, which may induce renal stone disease or alter kidney function due to urine crystals.

[Cardioprotection: an essential component for predialysis chronic renal failure treatment]. / La cardioprotection: une composante essentielle du traitement de l'insuffisance rénale chronique dès le stade prédialytique.

Cardiovascular (CV) disease in uremic patients is a major concern to the nephrologist because it represents the main cause of morbidity and mortality in chronic renal failure patients, both predialysis and while on dialysis therapy. CV mortality is 3 to 20 times higher in dialysis patients than in the general population at similar age. Of note, a high prevalence of CV comorbidity is already present at start of maintenance dialysis, and is predictive of subsequent mortality on dialysis. CV disease progresses over years prior to the onset of ESRD, because risk factors develop from the early stage of chronic renal insufficiency. However, CV disease may be prevented or attenuated in patients who benefit from early, regular care of CV risk factors. Mechanisms of uremic cardiopathy, the major cause of mortality in uremic patients, are multifactorial and their effects are cumulative. Risk factors for left ventricular hypertrophy are hypertension, anemia, fluid overload and arteriosclosis, all of which are amendable by therapy. Risk factors for accelerated atherosclerosis, responsible for ischemic cardiopathy and myocardial infarction, are both common factors (e.g., hypertension, tobacco smoking and diabetes) and factors more specific for the uremic state (e.g., dyslipidemia, hyperhomocysteinemia and oxidative stress), all of which also are amendable by proper therapy. As a result, mixed hypertensive and ischemic cardiomyopathy develops, ultimately leading to cardiac failure, together with accidents resulting from valvular and arterial calcifications (favored by calcium-phosphate disorders), and from occlusion of coronary, cerebral and peripheral arteries. Cardioprotective therapy thus has become a cornerstone in the management of chronic renal failure patients, in conjunction with renoprotective therapy. Cardioprotective strategy involves optimal treatment of hypertension, anemia, fluid overload, dyslipidemia, hyperhomocysteinemia and calcium-phosphate disorders, and smoking cessation. To achieve a maximal efficacy, such treatment has to be initiated as early as possible in the course of renal failure. Because of its complexity, the integrated combined nephrotective and cardioprotective therapy requires early and sustained guidance by a nephrologist throughout the whole predialysis period.

Longer duration of predialysis nephrological care is associated with improved long-term survival of dialysis patients.

BACKGROUND: Late nephrological referral of chronic renal failure patients has been shown to be associated with high morbidity and short-term mortality on dialysis. However, the impact of predialysis nephrological care duration (PNCD) on the long-term survival of dialysis patients had not been evaluated. METHODS: We studied data from all 1057 consecutive patients who started dialysis treatment at the Necker Hospital from 1989 to 1998 (mean age at start of dialysis 53.8+/-17.2 years (range 18-91 years), excluding from analysis patients who presented with acute renal failure (n=60) or advanced malignancy (n=35). We evaluated the effects of PNCD and clinical risk factors on all-cause mortality after long-term follow-up on dialysis. RESULTS: Among the 1057 patients analysed (13.2% diabetics), PNCD was <6 months in 258 patients, 6-35 months in 267 patients, 36-71 months in 227 patients and >or=72 months in 307 patients. Cardiovascular (CV) morbidity, namely a history of myocardial or cerebral infarction, peripheral arteriopathy, and/or cardiac failure, before starting dialysis was 39.6% and 37.4%, respectively, in patients followed for <6 months or 6-35 months, compared with 24.4% in those followed for 36-71 months and 19.9% in those followed for >or=72 months (P<0.001). Five-year survival was significantly lower in patients with a PNCD of <6 months (59+/-4.1%) than for 36-71 months or >or=72 months (77.1+/-3.7 and 73.3+/-3.6%, respectively, P<0.001), but similar to those followed for 6-35 months (65.3+/-3.9%, NS). By Cox proportional hazard analysis, PNCD <6 months, age, diabetes and prior CV disease were independent predictive factors of all-cause death on dialysis. CONCLUSIONS: This study provides suggestive evidence that longer duration of regular nephrological care in the predialysis period, at least for several years prior to the start of dialysis, is associated with a better long-term survival on dialysis. Such data strongly support the argument for early referral and regular nephrological care of chronic renal failure patients.

[Course of chronic renal failure epidemiology and prediction of maintenance dialysis needs in France]. / Evolution de l'épidémiologie de l'insuffisance rénale chronique et prévision des besoins en dialyse de suppléance en France.

Epidemiology of diseases leading to end-stage renal disease (ESRD) in France has greatly changed over the past decades, with the disappearance of type 1 primary membranoproliferative glomerulonephritis, and the increased incidence of both vascular and diabetic nephropathies. The incidence of ESRD is continuously growing, by about 4% per year, with a present rate of more than 100 new patients per million population (pmp) per year. The rise in incidence is mainly observed in older subjects. As a consequence, one may predict a relentless increase in the next years, in parallel with the relentless ageing of the population. The number of ESRD patients on maintenance dialysis is also growing, by nearly 4% per year. The present prevalence is 433 pmp in the Ile de France area, ranging from 268 pmp in subjects aged 15-59 years, to as high as 980 pmp in the population aged 60 years or more. Whereas the number of in-center treated patients has remained quite stable over the past five years, the total number and proportion of out-center treated patients is continuously increasing, as expected, thanks to the development of self-care hemodialysis and of peritoneal dialysis. These data may help predict logistic requirements for maintenance dialysis in the next years.

[Indications and preparations for kidney dialysis]. / Indication et préparation au traitement de suppléance rénale.

Every patient with end-stage renal failure, at any age and whatever the type of renal disease, is a legitimate candidate to maintenance dialysis. Contraindications are infrequent and based purely on medical considerations, such as profound and irremediable alteration of physical and/or mental condition. In patients regularly managed dialysis is decided electively on the basis of laboratory criteria in the absence of clinical uremic manifestations other than fatigue, anorexia or nausea. The most widely accepted criterion is a level of creatinine clearance estimated by the Cockcroft-Gault formula between 7 and 10 mL/min/1.73 m2. Psychological preparation of the patient to dialysis is essential and should not be delayed until the advanced stage. Medical preparation involves prophylactic vaccination against virus B hepatitis and creation of a native arteriovenous fistula when hemodialysis is the scheduled option. Every patient should receive in time clear and complete information on the various technical methods of dialysis, in order to allow him an informed choice.

Homocyst(e)ine, oxidative stress, and endothelium function in uremic patients.

Moderate hyperhomocyst(e)inemia and impaired endothelium-dependent vasodilatation are present in uremic patients. However, the precise mechanism(s) underlying the link between moderate hyperhomocyst(e)inemia and endothelium dysfunction in uremic patients remains to be determined. Experimental and clinical evidence have led to the suggestion that moderate hyperhomocyst(e)inemia may predispose to endothelium dysfunction through a mechanism that involves generation of reactive oxygen species and a decrease in nitric oxide bioavailability. Recent preliminary findings in uremic patients provide support for some aspects of this suggestion. These data must be confirmed in additional studies. Moreover, the relative importance of homocysteine-induced oxidant stress versus other potential mechanisms of endothelium dysfunction in these patients remains to be determined.

Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients.

BACKGROUND: Partial correction of anaemia with recombinant human erythropoietin (rHuEpo) has been shown to markedly improve the general condition and quality of life of predialysis patients, but the effects of rHuEpo therapy on blood pressure and the rate of progression of chronic renal failure (CRF) are still disputed. In particular, no study evaluated the time duration until the start of maintenance dialysis in treated patients, compared to untreated predialysis patients. METHODS: We retrospectively evaluated the rate of decline of creatinine clearance (Delta Ccr) and the duration of the predialysis period in 20 patients with advanced CRF treated with rHuEpo (Epo+ group), and in 43 patients with a similar degree of CRF but with less marked, asymptomatic anaemia, not requiring rHuEpo therapy (Epo- group). All patients were submitted to identical clinical and laboratory surveillance. All received similar oral supplementation with B(6), B(9), and B(12) vitamins and oral iron supplementation. Maintenance dose of subcutaneous epoetin was 54.3+/-16.5 U/kg/week (median dose 3300 U/week). RESULTS: Initial and final haemoglobin (Hb) levels were 8.8+/-0.7 and 11.3+/-0.9 g/dl in the Epo+ group, vs 10.9+/-1.2 and 9.5+/-0.9 g/dl in the Epo- group. In the Epo+ group, Delta Ccr declined from 0.36+/-0.16 during the preceding 24 months to 0.26+/-0.15 ml/min/ 1.73 m(2)/month after the start of rHuEpo therapy (P<0.05). No significant variation was observed in the Epo- group. Time duration until the start of dialysis was 16.2+/-11.9 in the Epo+ group, compared to 10.6+/-6.1 months in the Epo- group (P<0.01). Slowing of progression was observed in 10 Epo+ patients, whereas no significant variation in Delta Ccr occurred in the other 10. There was no difference in previous Delta Ccr rate, nor in Hb or blood pressure levels while on rHuEpo therapy between the two subgroups. CONCLUSIONS: Our study affords conclusive evidence that rHuEpo therapy did not result in accelerated progression of CRF in any treated predialysis patients, nor deleterious increase in blood pressure, but instead resulted in significant slowing of progression and substantial retardation of maintenance dialysis. Such encouraging results remain to be validated in a large prospective, randomized study.

[Urinary lithiasis of medical origin]. / Les lithiases urinaires d'origine médicamenteuse.

Analysis of 22,510 urinary calculi between January 1991 to July 2000 performed by infrared spectroscopy allows for separation of drug-induced urolithiasis into two categories: first, the drugs physically embedded in the stone (n = 238; 1.0 per cent), notably indinavir monohydrate (n = 126; 52.9 per cent), followed by triamterene (n = 43; 18.1 per cent), sulphonamides (n = 29; 12.2 per cent) and amorphous silica (n = 24; 10.1 per cent); second, the category of metabolic nephrolithiasis induced by drugs (n = 140; 0.6 per cent), involving mainly calcium and vitamin D supplementation (n = 56; 40.0 per cent) and carbonic anhydrase inhibitors (n = 33; 23.6 per cent). Composition of the stone depended not only on the inducer drug but also on the metabolic state of the patient. Today, drug-induced stones comprise about 1.6 per cent of all calculi in France. Physical analysis and therapeutic history recall of such patients are the keys to diagnosis. Medical care is based on drug avoidance or dose adjustment with increased diuresis and, if necessary, change in urinary pH.

[Epidemiology of end-stage kidney failure in the Ile-de-France: a prospective cooperative study in 1998]. / Epidémiologie de l'insuffisance rénale terminale en Ile-de-France: enquête coopérative prospective en 1998.

A prospective epidemiological study was conducted from January 1 to December 31, 1998 in the Ile-de-France district to determine the incidence and the prevalence of end-stage renal disease (ESRD) and the characteristics of the patients. All nephrology and dialysis units of the Ile-de-France district participated in the study. The total number of ESRD patients requiring maintenance dialysis was 1155 (including 86 kidney graft failures and 29 children) for a total population of 10.7 millions inhabitants, or 108/10(6)/year. The incidence of new ESRD patients was 100/10(6)/year. The mean age of first-dialyzed, adult patients was 59.8 +/- 16.8 years, with 21.6% aged > or = 75 years. Vascular renal diseases accounted for 22.5% and diabetic nephropathy for 20.6%. As a whole, 36.5% of patients were referred to the nephrologist less than 6 months before starting dialysis. In the latter, the median duration of hospitalization was 28 days, compared to only 3 days in patients cared for by the nephrologist for at least 6 months. Prevalence of patients on maintenance dialysis in the Ile-de-France district grew from 417 to 433/10(6) from the beginning until the end of year 1998, an increment of 3.8%, with an increase in the number of patients treated out-center by self-care hemodialysis or peritoneal dialysis.

Epidemiology of end-stage renal disease in the Ile-de-France area: a prospective study in 1998.

BACKGROUND: The objective of this study was to determine the incidence and prevalence of end-stage renal disease (ESRD) requiring maintenance dialysis in the Ile-de-France district (Paris area), and the characteristics of patients at start of dialysis. METHODS: This is a prospective epidemiological study with the cooperation of all dialysis facilities of the Ile-de-France district (population 10.7 million inhabitants as of March 1999). All consecutive ESRD patients who started dialysis from January 1 to December 31 1998, with demographic and clinical characteristics, and of the total number of patients on dialysis with their distribution according to dialysis modality were recorded. RESULTS: The total number of ESRD patients in 1998 was 1155, including 29 (2.5%) children aged < or =17 years and 86 (7.4%) returns to dialysis following kidney graft failure. Incidence of first-dialysed patients was 100 per million population (p.m.p.) and overall incidence, including returns from transplantation, was 108 p.m.p. The mean age of first-dialysed adult patients was 59.8+/-16.8 years, with 21.6% aged > or =75 years. Patients with vascular renal disease were 22.5% and those with diabetic nephropathy 20.6%. As a whole, 36.5% of patients were referred to the nephrologist < or =6 months before start of dialysis, including 32.2% referred < or =1 month before starting. Prevalence of cardiovascular disease was nearly twice as high in patients referred <6 months of starting dialysis than in those who benefited from effective nephrological care for >3 years in the predialysis period. By multivariate analysis, this difference persisted after adjustment for age and other confounding covariates. The total number of patients on maintenance dialysis increased from 417 to 433 p.m.p. (a yearly 3.8% increase) from the beginning to the end of 1998. CONCLUSION: This recent epidemiological study in a large French urban area indicates an annual incidence of 100 new ESRD patients p. m.p., with a high proportion of older, vascular and diabetic patients. Overall incidence, including returns from transplantation, reached 108 p.m.p. Cardiovascular disease was significantly less frequent in patients who received nephrological care for > or =3 years prior to start of dialysis than in late referred patients, underlining the benefits of early nephrological management of renal patients.

[Incidence of end-stage renal disease in Ile de France: a prospective epidemiological survey]. / Incidence de l'insuffisance rénale terminale en Ile de France: enquête épidémiologique prospective.

OBJECTIVES: To evaluate incidence and prevalence of patients with end-stage renal disease (ESRD) treated with maintenance dialysis in the Ile de France district in 1998. METHODOLOGY: Prospective epidemiologic inquiry with the cooperation of the 91 nephrology departments and dialysis facilities of the Ile de France district (total population: 10,695,300 inhabitants in March 1999), from January 1st to December 31st, 1998. Evaluation of the demographic and clinical characteristics of the 1155 patients accepted on maintenance dialysis in 1998, and recording of the total number of dialyzed patients at the beginning and at the end of the same year. RESULTS: The total number of ESRD patients was 1155, including 29 (2.5%) children aged < or = 17 years and 86 (7.4%) returns to dialysis following kidney graft failure. Incidence of ESRD in first-dialyzed patients was 100/million/year and overall incidence, including returns from transplantation, was 108/million/year. Mean age of the 1040 adult first-dialysis patients was 59 +/- 16.8 years, with a proportion of those aged > or = 75 years of 21.6%. Patients with vascular renal disease were 22.5% and those with diabetic nephropathy 20.6%. As a whole, 36.5% of patients were referred to the nephrologist < 6 months of starting dialysis. Prevalence of patients on supportive dialysis increased from 417 to 433 per million inhabitants (a 3.8% increase) from the beginning to the end of 1998, with the proportion of patients treated with self-care dialysis or peritoneal dialysis rising by 10%. From January 1995 to January 1999, prevalence of dialysis-treated ESRD patients rose by nearly 4% per year as a mean. CONCLUSION: Incidence of ESRD patients requiring maintenance dialysis in the Ile de France district reached 100/million in 1998, an increment of 4% per year over the past 4 years. The increase in incidence results from the increasing number of older patients, parallel to the ageing of general population, these patients having a high comorbidity mainly due to diabetes and atherosclerosis. Prevalence of dialysis-treated patients was 433/million population at the end of 1998. It rose at a similar rate as did incidence, although with a growing proportion of out-center dialysis.

[Medical treatment of cystinuria: evaluation of long-term results in 30 patients]. / Traitement médical de la cystinurie: évaluation des résultats à long terme chez 30 patients.

OBJECTIVE: Because urinary hyper-excretion of cystine is permanent in homozygous cystinuric patients, stone recurrence is frequent and may alter renal function. Identification of factors predictive of success of medical treatment (no further urological procedure required) is therefore needed to improve patient management. PATIENTS AND METHODS: Thirty adult patients with homozygous cystinuria and urolithiasis were referred to the nephrology department of the Necker Hospital from 1963 to 1999, with a mean follow-up of medical therapy of 10.5 +/- 8.4 years. The basal treatment schedule was hyperdiuresis and alkalinization with thiol derivative (D-penicillamine or tiopronine) added when needed. RESULTS: Overall incidence of urological procedures decreased from 0.33/pt-year in the pretherapeutic period to 0.15 on treatment (p < 0.01), a 55% reduction. Sixteen patients (53%) did not require any urological procedure during follow-up. The only significant difference between those patients and the other 14 in whom medical therapy failed was the daily urine volume (3.2 l/day in the former compared with 2.4 l/day in the latter, p < 0.001). CONCLUSION: Regular medical therapy was able to stop stone disease activity in the long term in more than half of the patients. Sustained hyperdiuresis, with a daily urine volume > 3 liters, appears as a major factor of therapeutic success, even in patients treated with thiols.

Medical treatment of cystinuria: critical reappraisal of long-term results.

PURPOSE: We evaluated long-term results of a contemporary medical therapeutic regimen in patients with cystinuria and analyzed factors predictive of therapeutic success. MATERIALS AND METHODS: A total of 27 adults with cystine urolithiasis were treated at our institution for 1.3 to 32 years (mean 11.6, overall 312 patient-years). We obtained data on the pre-referral period for 274 patient-years overall. Basic therapy included hyperdiuresis and alkalization. The thiols D-penicillamine or tiopronin were added when standard therapy failed to prevent new stones and stone growth or dissolve preexisting stones. X-ray and echography were performed every 4 months during the initial 2 years and every 6 months thereafter. RESULTS: In the pre-referral period 256 stone episodes occurred and 81 urological procedures were performed in 24 patients (0.93 and 0. 29 per patient-year, respectively). Nine patients were treated with added thiols. During the therapeutic period the incidence of stone episodes decreased to 66 (0.20 per patient-year, p <0.001), while the need for urological procedures decreased to 44 (0.14 per patient-year, p <0.001). No further urological procedures were required in 15 patients, including 4 treated with thiols. However, the remaining 12 patients, including 5 treated with thiols, underwent 1 to 7 procedures each (mean 0.26 per patient-year). In the 2 groups mean daily cystine excretion plus or minus standard deviation at baseline (863 +/- 253 versus 761 +/- 270 mg. daily) and mean urinary pH of about 7.4 did not differ significantly. However, daily urine volume was significantly higher in patients with arrested stone formation (3,151 +/- 587 versus 2,446 +/- 654 ml./24 hours, p = 0.006). CONCLUSIONS: Our study provides evidence that a regularly followed medical program based on high diuresis and alkalization with second line addition of thiols may arrest or markedly decrease cystine stone formation and preclude the need for urological procedures in more than half of the patients. However, patients poorly compliant with hyperdiuresis remain at risk for recurrence. We suggest that maintaining a daily urine volume of greater than 3 l. is essential for therapeutic success regardless of whether thiol derivatives are administered.

Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy.

UNLABELLED: Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. BACKGROUND: Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients. METHODS: In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin. RESULTS: Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time. CONCLUSIONS: Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.

Treatment of cystinuria.

Cystine urolithiasis is the only clinical expression of cystinuria, an autosomal recessive genetic defect of the transepithelial transport of cystine and other dibasic amino acids in the kidney. Stones form due to the increased excretion of cystine, which is poorly soluble at normal urine pH. Cystine stones are often resistant to extracorporeal shock wave lithotripsy, so that percutaneous surgery or ureteroscopy are the preferred techniques of stone extraction. Medical preventative treatment is based on high diuresis (>/=1.5 l/m(2) per day) well distributed throughout the day and night, and urine alkalinization up to pH 7.5 by means of sodium bicarbonate and/or potassium citrate. When these basal measures are ineffective at preventing stone recurrence or dissolving pre-existing stones, sulfhydryl agents such as D-penicillamine or tiopronin, which form highly soluble mixed disulfides with cystine moieties, are to be added to urine dilution and alkalinization, especially when cystine excretion is in excess of 750 mg/day (3 mmol/day). Frequent clinical and ultrasound follow-up is needed to encourage patient compliance and assess efficacy and tolerance of treatment.