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

Abstract

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 α‐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...

CKD and Its Risk Factors among Patients with Cystinuria

“…BP.160/100 mmHg was reported in 25.8% of cystinuric patients (17) and Dahlberg et al reported that 12.4% of cystinuric patients had HBP (36). It has also been reported that HBP was not more common in cystinuric patients than in patients with stones of other causes (17). After excluding risk factors known to be associated with HBP, the available data were too sparse to evaluate the prevalence of HBP in patients aged $40 years.…”

“…It is well known that cystinuric patients are overrepresented among nephrolithiasis patients with an acquired solitary kidney (27,28), and that they have significantly more nephrectomy than patients with calcium oxalate nephrolithiasis (15). The prevalence of nephrectomy varies from 7.7% to 20% among cystinuric patients (8,12,15,17,18,29). Stone-former patients with a single functioning kidney have a lower GFR than those with two functioning kidneys (28) and nephrectomy was shown to be a risk factor for elevated PCr in cystinuric patients (15).…”

“…However, the risk of CKD depends on the type of stones. Patients with hereditary stone diseases, including cystinuria, have been shown to be at higher risk of CKD than patients with other stone disease (12)(13)(14), and it has been reported that patients with cystine stones had a lower GFR than those with other kinds of stones (15)(16)(17). In the field of cystinuria, depending on the definition of renal impairment and duration of follow-up, the prevalence of CKD ranges from 5.8% (n=40) (15) to 30% (n=40) (18) in limited series.…”

Kidney Stones and the Risk for Chronic Kidney Disease

“…CKD is a recognized complication of kidney stones as a result of rare hereditary disorders (e.g., primary hyperoxaluria, Dent disease, 2-8-hydroxyadenine crystalluria, cystinuria) (3)(4)(5), whereby nephrocalcinosis or renal crystal deposition can lead to progressive loss of GFR and ESRD at a young age. In addition, infection stones (struvite) can lead to an obstructive nephropathy with staghorn calculi and are the leading cause of ESRD attributed to nephrolithiasis (6).…”

Chronic kidney disease in urolithiasis patients following successful extracorporeal shockwave lithotripsy

“…Urolithiasis is an equally highly prevalent disorder, affecting approximately 10% of the population in Western countries (5)(6) and Japan (7), and renal dysfunction is a well-described complication of urolithiasis (8)(9)(10)(11)(12)(13). Struvite stones, including staghorn calculi and severe stone disease caused by genetic disorders (e.g., primary hyperoxaluria, cystinuria, Dent disease and 2-8-hydroxyadenine crystalluria) (8)(9)(10), are universally considered the most frequent causes of urolithiasis-associated end-stage renal disease (ESRD). On the other hand, it is thought that the more common calcium oxalate or uric acid stones are a painful, but otherwise benign condition, infrequently leading to ESRD.…”