Variation in age at ESRD in autosomal dominant polycystic kidney disease.

摘要

BACKGROUND: Heterogeneity manifest as more severe disease in successive generations has been attributed to genetic anticipation in patients with autosomal dominant polycystic kidney disease (ADPKD). We evaluated variation in age at end-stage renal disease (ESRD) in ADPKD families for evidence of anticipation. STUDY DESIGN: Retrospective. SETTING & PARTICIPANTS: 413 families with ADPKD seen at our single center between 1985 and 2004 (including 95 families with documented polycystic disease type 1 [PKD1] and 213 ADPKD families with parents born before 1930). PREDICTOR: Generational status. OUTCOME: Age at ESRD onset. MEASUREMENTS: Time to ESRD was evaluated by using survival analysis, Cox regression, and descriptive statistics. Unstable trinucleotide repeat expansion was evaluated by means of genotyping in 6 PKD1 families. RESULTS: We analyzed 413 ADPKD families (1,391 parent-offspring pairs) with known age at ESRD or last known age without ESRD (informative pairs). There was no difference in age at ESRDbetween parents and offspring by means of Cox regression after adjusting for correlations among family members and sex (hazard ratio, 1.019; 95% confidence interval, 0.919 to 1.13; P = 0.7). Similar analysis of PKD1 informative pairs and those with parents born before 1930 showed no differences in age at ESRD. Male ADPKD patients were 42% more likely to reach ESRD (P < 0.001), and male patients with documented PKD1 were 41% more likely to reach ESRD (P = 0.01) than female patients. LIMITATIONS: Hypertension treatment unknown. CONCLUSIONS: We found no evidence for anticipation of ESRD in patients with ADPKD; thus, the observed variation in age at ESRD may result from other genetic, sex, or environmental causes.