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Background and objectives Cystinuria is an autosomal recessive disorder affecting renal cystine reabsorption; it causes 1% and 8% of stones in adults and children, respectively. This study aimed to determine epidemiologic and clinical characteristics as well as comorbidities among cystinuric patients, focusing on CKD and high BP.Design, setting, participants, & measurements This retrospective study was conducted in France, and involved 47 adult and pediatric nephrology and urology centers from April 2010 to January 2012. Data were collected from 442 cystinuric patients.Results Median age at onset of symptoms was 16.7 (minimum to maximum, 0.3-72.1) years and median diagnosis delay was 1.3 (0-45.7) years. Urinary alkalinization and cystine-binding thiol were prescribed for 88.8% and 52.2% of patients, respectively, and 81.8% had at least one urological procedure. Five patients (1.1%, n=4 men) had to be treated by dialysis at a median age of 35.0 years (11.8-70.7). Among the 314 patients aged $16 years, using the last available plasma creatinine, 22.5% had an eGFR$90 ml/min per 1.73 m 2 (calculated by the Modification of Diet in Renal Disease equation), whereas 50.6%, 15.6%, 7.6%, 2.9%, and 0.6% had an eGFR of 60-89, 45-59, 30-44, 15-29, and ,15, respectively. Among these 314 patients, 28.6% had high BP. In multivariate analysis, CKD was associated with age (odds ratio, 1.05 [95% confidence interval, 1.03 to 1.07]; P,0.001), hypertension (3.30 [1.54 to 7.10]; P=0.002), and severe damage of renal parenchyma defined as a past history of partial or total nephrectomy, a solitary congenital kidney, or at least one kidney with a size ,10 cm in patients aged $16 years (4.39 [2.00 to 9.62]; P,0.001), whereas hypertension was associated with age (1.06 [1.04 to 1.08]; P,0.001), male sex (2.3 [1.3 to 4.1]; P=0.003), and an eGFR,60 ml/min per 1.73 m 2 (2.7 [1.5 to 5.1]; P=0.001).Conclusions CKD and high BP occur frequently in patients with cystinuria and should be routinely screened.

Human multidrug resistance protein 2 (MRP2, encoded by ABCC2) is involved in active efflux of anionic drugs such as methotrexate. MRP2 is expressed on the luminal side of hepatocytes and renal proximal tubular cells, indicating an important role in drug elimination. We postulated that loss-of-function mutations in ABCC2, which are involved in the Dubin-Johnson syndrome, may be associated with impaired methotrexate elimination and an increased risk of toxicity. We studied the biological phenotype and ABCC2 coding sequence in a patient receiving a high-dose methotrexate infusion for large B-cell lymphoma and who had an unusual pharmacokinetic profile, mainly characterized by a three-fold reduction in the methotrexate elimination rate. This resulted in severe methotrexate over-dosing and reversible nephrotoxicity. An inversion of the urinary coproporphyrin isomer I/III ratio (a specific biological marker of the Dubin-Johnson syndrome) was observed in this patient. Genetic analysis of ABCC2 identified a heterozygous mutation replacing a highly conserved arginine by glycine in the cytoplasmic part of the second membrane-spanning domain (position 412 of MRP2), a region associated with substrate affinity. This genetic variant was not found in a control population. Functional analysis in transiently transfected Chinese hamster ovary cells revealed a loss of transport activity of the G412 MRP2 mutant protein. An ABCC2 mutation altering MRP2-mediated methotrexate transport and resulting in impaired drug elimination and subsequent renal toxicity was identified. Candidates for methotrexate therapy should be considered for MRP2 functional testing.

HIV-infected patients who are on hemodialysis have a worse prognosis than noninfected patients who are on hemodialysis. Their outcome in the highly active antiretroviral therapy (HAART) era remains unclear. Outcomes in patients who were enrolled in the French Dialysis in HIV/AIDS (DIVA) cohort were determined in a 2-yr prospective follow-up. All HIV-infected patients who were on hemodialysis in France on January 1, 2002, were included and followed prospectively until January 1, 2004. Patients' survival was examined by Kaplan-Meier method, and mortality risk factors were examined using uni-and multicovariate analyses. Survival was compared with that of 584 hemodialysis patients who did not have HIV or diabetes and were enrolled in the French Dialysis Outcomes and Practice Patterns Study II (DOPPS II) in the same period (after standardization for the average age, gender, and ethnicity of the DIVA cohort). A total of 27,577 patients were receiving hemodialysis in France at the beginning of the study; 164 (0.59%) were infected with HIV, 72% were male, mean age was 44.8 ؎ 10.9 yr, and 65% were black. The 2-yr survival rate was 89 ؎ 2% and statistically indistinguishable from the survival of the French cohort extracted from the DOPPS II study. Significant mortality risk factors were low CD4 cell count (hazard ratio S ince 1996, the use of highly active antiretroviral therapy (HAART) has changed HIV infection from a subacute fatal condition to a chronic systemic disease. We now have to face many long-term comorbid conditions that HIV patients once did not have time to develop. Nearly every organ of the human body can be affected, and all caregivers have to deal with an increasing number of HIVinfected patients. Renal failure can be a direct consequence or an associated condition of HIV infection. HIV associated nephropathy (HIVAN) first was described in 1984 (1), and its prevalence has decreased significantly in the HAART era as compared with the pre-HAART era (2). Advanced HIV disease, as indicated by a low CD4 cell count, is associated with subsequent development of renal disease (3), but many other causes now may lead to renal failure in patients with HIV, including drug-induced toxicity, hypertensive nephroangiosclerosis, and diabetes. ESRD substantially increases the risk for death, cardiovascular disease, and the use of specialized health care (4). Despite 20 yr of intensive HIV research, very little is known about mortality risk factors in ESRD in HIVinfected patients. HIV-infected patients who are on hemodialysis are exposed to a high risk for death because their status combines the cumulative risks of both hemodialysis and HIV infection (5). Cardiovascular diseases, immunosuppression, anemia, weight loss, and osteodystrophy are known to be consequences of both hemodialysis and HIV infection (5-7). Patients with ESRD and HIV are younger, less frequently have diabetes, and have less hypertension than the general population of hemodialysis patients. Therefore, it is very arduous to guess what their survival has b...