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

ABSTRACT: 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.Retrospective.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).Generational status.Age at ESRD onset.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.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.Hypertension treatment unknown.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.

SUBMITTER: Reed BY

PROVIDER: S-EPMC2747334 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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

Reed Berenice Y BY McFann Kim K Bekheirnia Mir R MR Nobakhthaghighi Niloofar N Masoumi Amirali A Johnson Ann M AM Shamshirsaz Alireza A AA Kelleher Catherine L CL Schrier Robert W RW

American journal of kidney diseases : the official journal of the National Kidney Foundation 20080201 2

<h4>Background</h4>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.<h4>Study design</h4>Retrospective.<h4>Setting & participants</h4>413 families with ADPKD seen at our single center between 1985 and 2004 (including 95 families with documented polycy ...[more]

PMID: 18215695

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Project description:Autosomal dominant polycystic kidney disease (ADPKD) is amenable to early detection and specialty care. Thus, while important to patients with the condition, end-stage renal disease (ESRD) from ADPKD also may be an indicator of the overall state of nephrology care.Retrospective cohort study of temporal trends in ESRD from ADPKD and pre-renal replacement therapy (RRT) nephrologist care, 2001-2010 (n = 23,772).US patients who initiated maintenance RRT from 2001 through 2010 (n = 1,069,343) from US Renal Data System data.ESRD from ADPKD versus from other causes for baseline characteristics and clinical outcomes; interval 2001-2005 versus 2006-2010 for comparisons of cohort of patients with ESRD from ADPKD.Death, wait-listing for kidney transplant, kidney transplantation.US census data were used as population denominators. Poisson distribution was used to compute incidence rates (IRs). Incidence ratios were standardized to rates in 2001-2002 for age, sex, and race/ethnicity. Patients with and without ADPKD were matched to compare clinical outcomes. Poisson regression was used to calculate IRs and adjusted HRs for clinical events after inception of RRT.General population incidence ratios in 2009-2010 were unchanged from 2001-2002 (incidence ratio, 1.02). Of patients with ADPKD, 48.1% received more than 12 months of nephrology care before RRT; preemptive transplantation was the initial RRT in 14.3% and fistula was the initial hemodialysis access in 35.8%. During 4.9 years of follow-up, patients with ADPKD were more likely to be listed for transplantation (IR, 11.7 [95% CI, 11.5-12.0] vs 8.4 [95% CI, 8.2-8.7] per 100 person-years) and to undergo transplantation (IR, 9.8 [95% CI, 9.5-10.0] vs 4.8 [95% CI, 4.7-5.0] per 100 person-years) and less likely to die (IR, 5.6 [95% CI, 5.4-5.7] vs 15.5 [95% CI, 15.3-15.8] per 100 person-years) than matched controls without ADPKD.Retrospective nonexperimental registry-based study of associations; cause-and-effect relationships cannot be determined.Although outcomes on dialysis therapy are better for patients with ADPKD than for those without ADPKD, access to predialysis nephrology care and nondeclining ESRD rates may be a cause for concern.

Project description:BACKGROUND & AIMS:Polycystic liver disease (PLD), the most common extrarenal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent as a result of increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes are associated with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes. METHODS:We performed a cross-sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I-converting enzyme inhibitor and angiotensin II-receptor blocker was superior to the inhibitor alone, and whether low blood pressure (<110/75 mm Hg) was superior to standard blood pressure (120-130/70-80 mm Hg), in delaying renal cystic progression in 558 patients with ADPKD, stages 1 and 2 chronic kidney disease, and hypertension (age, 15-49 y). RESULTS:We found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had a relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism were associated with PLD severity. Higher liver volumes were associated with a lower quality of life. CONCLUSIONS:Hepatomegaly is common even in early stage ADPKD and is not accounted for by cysts alone. Parenchymal volumes were larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations, even among patients without cysts. The severity of PLD was associated with altered biochemical and hematologic features, as well as quality of life. ClinicalTrials.gov identifier: NCT00283686.

Dataset Information

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

Publications

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

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