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Evaluation of Nephrolithiasis in Autosomal Dominant Polycystic Kidney Disease Patients

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Evaluation of Nephrolithiasis in Autosomal Dominant Polycystic Kidney Disease Patients Evaluation of Nephrolithiasis in Autosomal Dominant Polycystic Kidney Disease Patients Jose´L. Nishiura,* Rodrigo F.C.A. Neves,† Samara R.M. Eloi,* Susan M.L.F. Cintra,* Sergio A. Ajzen,† and Ita P. Heilberg* *Nephrology Division and †Radiology Department, Universidade Federal de Sa˜o Paulo, Sa˜o Paulo, Brazil Background and objectives: Nephrolithiasis (LIT) is more prevalent in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. Renal ultrasonography may underdetect renal stones because of difficulties imposed by parenchymal and/or cyst wall calcifications. Design, setting, participants, & measurements: A total of 125 patients with ADPKD underwent ultrasonography and unenhanced computed tomography (CT) scan, routine blood chemistry, and spot and 24-h urine collections. Results: CT scan detected calculi in 32 patients, including 20 whose previous ultrasonography revealed no calculi. The .percentage of hypocitraturia was high but not statistically different between patients with ADPKD؉LIT or ADPKD Hyperuricosuria and distal renal tubular acidosis were less prevalent but also did not differ between groups, whereas hyperoxaluria was significantly higher in the former. Hypercalciuria was not detected. Renal volume was significantly higher in patients with ADPKD؉LIT versus ADPKD, and a stepwise multivariate logistic regression analysis showed that a renal volume >500 ml was a significant predictor of LIT in patients with ADPKD and normal renal function, after adjustments for age and hypertension. Conclusions: CT scan was better than ultrasonography to detect LIT in patients with ADPKD. Larger kidneys from patients with ADPKD were more prone to develop stones, irrespective of the presence of metabolic disturbances. Clin J Am Soc Nephrol 4: 838–844, 2009. doi: 10.2215/CJN.03100608 utosomal dominant polycystic kidney disease (AD- was to seek the presence of renal stones in patients with AD- PKD) is one of the most common inherited diseases PKD through both renal ultrasound and unenhanced helical CT A in humans, affecting 4 to 6 million people world- scan and to evaluate the metabolic profile of such patients. wide, and accounts for ESRD in 7 to 10% of hemodialysis and renal transplant patients (1). A frequent association of nephro- Materials and Methods lithiasis with ADPKD has been reported (2,3) to be responsible A total of 312 patients were referred to the Polycystic Kidney Disease for significant morbidity because of flank pain, hematuria, and Unit of the Nephrology Division, Universidade Federal de Sa˜o Paulo urinary tract infection. Patients with ADPKD may be predis- (Sa˜o Paulo, Brazil), because of the presence of an affected progenitor or posed to stone formation because of a structural abnormality sibling with ADPKD. Abdominal and renal ultrasound were performed secondary to cyst growth, renal tubular stasis, metabolic disor- in the Radiology Department of the same institution in all cases by a ders, or a combination of these factors (4,5). single consultant radiologist using a Siemens Antares ultrasound sys- tem (Erlangen, Germany) and a 3- to 5-MHz convex-array transducer. Renal ultrasound may underdetect nephrolithiasis in patients The sonographic diagnosis of ADPKD was confirmed in 125 patients, with ADPKD because of the frequent occurrence of renal cal- based on criteria established by Ravine et al. (6). All 125 patients who cifications. Unenhanced helical computed tomography (CT) were recruited on the basis of the ultrasound findings were submitted provides an excellent technique for detecting calcifications and to a clinical evaluation and to an unenhanced CT scan (Picker PQ 5000, for distinguishing renal calculi from cyst calcifications in pa- Cleveland, OH), by which hepatic cysts could be also identified. On CT tients with ADPKD (3). scans, renal cyst calcifications were diagnosed by their relationship to Considering the diagnostic difficulties and the increased cysts, location outside the renal collecting system, and morphology morbidity of nephrolithiasis associated with ADPKD, as well as (e.g., curvilinear calcification), and the presence of associated nephro- ϩ the limited knowledge of the metabolic and/or anatomic fac- lithiasis (ADPKD LIT) was defined by images of calculi within the tors that contribute to stone formation, the aim of this study urinary collecting system. Patients were considered to present LIT only when ultrasound images of calculi were further confirmed by CT scan. The maximum time lapse between performance of ultrasound and CT scan was 30 d. On ultrasound, the number of cysts was determined, and Received June 25, 2008. Accepted January 20, 2009. the size of the largest cyst in each kidney was measured. Kidney length, Published online ahead of print. Publication date available at www.cjasn.org. width, and anteroposterior diameter were also determined. Renal vol- ume was then calculated using a standard formula of a modified Correspondence: Dr. Ita P. Heilberg, Universidade Federal de Sa˜o Paulo, Ne- ellipsoid for each kidney as follows: Renal volume ϭ 4/3 ␲ ϫ (antero- phrology Division, Rua Botucatu 740, Vila Clementino, Sa˜o Paulo-SP, 04023-900, ϩ 2 ϫ Brazil. Phone: 55-11-5574-6300; Fax: 55-11-5573-9652; E-mail: ipheilberg@nefro. posterior diameter width/4) length/2 (7). To compare renal epm.br volume between ADPKD groups with or without associated nephroli- Copyright © 2009 by the American Society of Nephrology ISSN: 1555-9041/404–0838 Clin J Am Soc Nephrol 4: 838–844, 2009 Nephrolithiasis in ADPKD 839 thiasis, we considered the volume of the kidney(s) containing the McNemar test. Continuous variables were compared between groups stone(s) in the former group and the highest kidney volume among the using Mann-Whitney test. P Ͻ 0.05 was considered statistically signif- two kidneys in the latter. Written consent was obtained from all pa- icant. A univariate logistic regression analysis was used to estimate the tients, and the local ethics committee approved the study. odds ratio for the occurrence of nephrolithiasis with the variables age, Hypertension was considered on the basis of a history of hyperten- gender, hypertension, renal volume, number and size of cysts, and sion, present BP measurements, or actual/past use of antihypertensive creatinine clearance. A stepwise multiple regression analysis was per- medications. Serum parameters included routine blood chemistry (cre- formed to determine the independent variable(s) related to nephroli- atinine, sodium, potassium, calcium, uric acid, and chloride). A blood thiasis. Receiver operator characteristic curve analysis was used to sample for venous blood gases was drawn anaerobically into an hep- determine the cutoff value of a significant renal volume with respect to arinized tube and analyzed immediately after collection whenever the risk for nephrolithiasis occurrence. possible or kept on ice for no longer than 30 min for plasma bicarbonate (HCO3) determination, through venous blood gas analysis. A 24-h Results urine sample was delivered for determination of urine volume, cal- ADPKD was identified in 125 patients (80 female/45 male) cium, uric acid, citrate, oxalate, sodium, potassium, creatinine, urea, aged 15 to 80 yr, being distributed among 69 families. Neph- magnesium, and phosphate, and the determined creatinine clearance rolithiasis was disclosed in 35 of these 125 patients, with 32 was adjusted for body surface area. Thiazides were withdrawn at least cases detected on CT scan including 20 that were not visible at 72 h before urine collection. A morning 12-h fasting spot urine sample ultrasound. Figure 1 illustrates a case of a barely visible calcu- (under conditions of water restriction) was collected for urinary pH (upH), osmolality, microalbuminuria, and culture. In the presence of a lus at ultrasound, clearly shown in a CT scan. Three patients positive urine culture (Ͼ105 colony-forming units/ml), the results of did not present calculi on CT scan, but one of them had been upH and albumin were not considered and the spot urine analysis was previously submitted to extracorporeal shock wave lithotripsy repeated in a further occasion, after the treatment of the urinary tract and the other two had passed calculi. As shown in Table 1, the infection. upH was measured by a pHmeter. Distal renal tubular aci- proportion of calculi detected by CT scan in the whole sample dosis (dRTA) was considered in cases of fasting upH Ͼ5.5 in the was statistically higher than the one detected by ultrasound (25 Ͻ presence of systemic acidosis, defined by a plasma HCO3 22 mEq/L versus 15%; P Ͻ 0.021). A higher percentage of patients with (complete form). In the absence of spontaneous acidosis, patients were further submitted to an ammonium chloride (NH4Cl) loading test to detect incomplete forms of dRTA, as described previously (8). Briefly, urine was collected for a period of 3 h, after2hofNH4Cl ingestion (0.1 g/kg body wt), and pH and net acid excretion were determined. A reduction of urinary pH Ͻ5.5 coupled with a two-fold increase in ammonium excretion and a three-fold increase in titratable acidity were considered to be an adequate response to the acid load. Ammonium excretion was also determined in 10 healthy subjects (one female and nine male) from the laboratory staff for comparisons with patients with ADPKD. Decreased renal concentrating capacity was defined by urine osmolality Ͻ800 mOsm/kg after 12 h of water restriction, and normal ranges for microalbuminuria were Ͻ15 ␮g/min. Hypercalciuria was defined as calcium Ն4 mg/kg body wt, hyperuricosuria as uric acid Ͼ750 or 800 mg/24 h (for female or male, respectively), hypocitraturia as citrate Ͻ320 mg/24 h, hyperoxaluria as urine oxalate Ͼ45 mg/24 h, and hypomagnesuria as urinary magnesium Ͻ70 mg/24 h as described previously (9). Metabolic disturbances and urinary acidification tests were evaluated only in patients who had normal renal function and a creatinine clearance Ͼ60 ml/min per 1.73 m2 (10). Ion activity product (AP) with respect to calcium oxalate (Tiselius Index) was calculated as Ϫ follows: AP(CaOx) ϭ 1.9 ϫ calcium0.84 ϫ oxalate ϫ citrate 0.22 ϫ Ϫ Ϫ magnesium 0.12 ϫ volume 1.03 (11).
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