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

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 ESRD between 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.

Relationship between urinary albumin excretion and left ventricular mass with mortality in patients with type 2 diabetes.

Increased urinary albumin excretion (UAE) has been shown to be associated with increased cardiovascular mortality in patients with type 2 diabetes. This study evaluated whether the association between UAE and cardiovascular mortality in 880 patients with type 2 diabetes was related to an increase in left ventricular mass (LVM). LVM was estimated by electrocardiographic index, namely adjusted Cornell voltage. LVM was significantly different between the stages of albuminuria (8.17 +/- 0.12 in normoalbuminuric, 9.05 +/- 0.21 in microalbuminuric, and 10.30 +/- 0.30 in overt albuminuric patients; P < 0.001). There also was a positive correlation between log UAE and LVM independent of BP. During 5 yr of follow-up, survivors had significantly lower LVM (8.62 +/- 0.11 versus 9.88 +/- 0.45; P = 0.0140) and lower UAE (154.60 +/- 16.53 versus 446.62 +/- 114.11; P = 0.0003) than nonsurvivors. The results indicate that patients with type 2 diabetes and increased UAE should be evaluated for increased LVM as an important and potentially reversible cardiovascular risk factor.

Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome.

BACKGROUND: The natural history of autosomal-dominant polycystic kidney disease (ADPKD) has not been well described in children and infants. METHODS: The present study analyzed the characteristics of 46 ADPKD children diagnosed before 18 months of life (VEO) and 153 children diagnosed between 18 months of age and 18 years of age (non-VEO). RESULTS: VEO children had more cysts and larger renal volumes than non-VEO children when adjusted for age. In both VEO and non-VEO children, the presence of signs or symptoms at the time of diagnosis as well as the presence of hematuria or proteinuria at the study visit were associated with larger renal volumes. Children diagnosed early (VEO) or diagnosed due to signs or symptoms were also more likely to have high blood pressure. Two VEO children and no non-VEO children reached end-stage renal disease during follow-up. CONCLUSION: In contrast to many published case reports suggesting the occurrence of early end-stage renal disease in VEO children, the results of the present study were much more optimistic. Over 90% of the VEO children maintained preserved renal function well into childhood.