Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.

BACKGROUND: Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS: The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS: Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS: Small sample size of this case series. CONCLUSIONS: Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.

Primary high-dose intradermal hepatitis B vaccination in hemodialysis: cost-effectiveness evaluation at 2 years.

Reinforced hepatitis B (HB) vaccination schedules have been tested in nonresponsive hemodialysis (HD) patients. Primary high-dose intradermal (ID) vaccination in HD has been proposed in one study with higher seroconversion rate, but no cost analysis was made. The aim of this prospective study was to confirm this previous report and focus on a cost-effectiveness evaluation of the thorough vaccination with a maintenance program. Thirty-five chronic incident HD patients received primary ID HB vaccination with a reinforced schedule (20 microg Engerix-B every 2 weeks). Revaccination with a monthly single ID dose of 20 microg was performed whenever anti-HBs titer fell under 20 IU/L and continued until a titer of 20 U/L was reached. Outcome measures were cumulative seroconversion rates, mean levels of anti-HBs, maintenance booster doses, rate of seroprotection at the end of the 2-year follow-up and subsequent costs. The present study was associated with an earlier peak of anti-HBs titer (3.9+/-1.7 months) and a higher cumulative seroconversion rate (96.9%) after 1 year. Moreover, a low-booster shot (17.4 microg) of ID Engerix-B/year/patient confers a 100% seroprotection for all responders for a second-year period. The mean cost of our schedule is 127.7 euro/patient for a 2-year period, revaccination included. This current study demonstrates that primary reinforced ID HB vaccination with a maintenance program for a 2-year period warrants the best cost-effectiveness ratio with rapid and sustained seroprotection in almost all HD patients.

High prevalence of fenfluramine-related aortic regurgitation in women with end-stage renal disease secondary to Chinese herb nephropathy.

BACKGROUND: Non-controlled studies have noted a high prevalence of valvular regurgitation in patients with Chinese herb nephropathy; most of these patients had taken appetite suppressants. We aimed to determine the prevalence of valvular regurgitation and the role of appetite suppressants in patients with Chinese herb nephropathy. METHODS: This case-controlled echocardiographic study included 40 patients with end-stage renal failure due to Chinese herb nephropathy and 37 age-matched controls with end-stage renal disease due to nephropathy of other origin. Quantification of cumulative doses of appetite suppressants was performed. RESULTS: Aortic regurgitation was detected in 52.5% of patients with Chinese herb nephropathy, 72+/-1 months after stopping appetite suppressants, and in 21.6% of controls (P=0.009). No difference was found in the incidence of mitral or tricuspid regurgitation. A history of slimming medication was the only significant determinant for aortic regurgitation (P=0.009). Higher cumulative doses of Chinese herbs, (dex)fenfluramine and diethylpropion were observed in patients with Chinese herb nephropathy with, when compared to those without, aortic regurgitation. The dose-response relationship between the cumulative dose of drugs and the presence of aortic regurgitation was significant for fenfluramine only (chi-square=5.16, P=0.024). CONCLUSIONS: Six years after stopping appetite suppressants, aortic regurgitation remains highly prevalent among patients with end-stage Chinese herb nephropathy. The dose-related association with fenfluramine intake strongly confirms a determinant pathogenic role of anorectic drugs.