Population-Based Screening for Family History of End-Stage Renal Disease among Incident Dialysis Patients

Abstract

Background: We determined the familial aggregation of end-stage renal disease (ESRD) in a large, population-based sample of incident ESRD cases to assess the feasibility of developing a targeted screening and prevention program directed at members of families at high risk for kidney disease. Methods: Between January 1, 1995, and December 31, 2003, incident dialysis patients in ESRD Network 6 facilities were asked to complete a voluntary questionnaire on family history (FH) of ESRD. Cases with ESRD attributed to Mendelian diseases or urologic causes were excluded. FH was considered present if first- or second-degree relatives had ESRD. De-identified FH data were collated with demographic data at dialysis initiation. Results: More than 46% of eligible patients (25,883/55,929) provided FH information and 22.8% (5,901/25,883) of these reported having a FH of ESRD. FH of ESRD was positively associated with female gender, earlier age at ESRD onset, and primary cause of ESRD, and negatively associated with white race. FH associations with age, race, gender, and primary cause of renal failure remained statistically significant after simultaneous adjustment in a multivariate logistic regression model. Conclusions: Approximately23% of incident dialysis patients have close relatives with ESRD. Far more are likely to have relatives with clinically silent proteinuria or chronic kidney disease (CKD), both risk factors for future cardiovascular events and ESRD. Physicians caring for patients with CKD should be aware of the marked familial aggregation of ESRD and consider focusing screening efforts on high-risk family members in an attempt to slow the exponential growth rate of kidney disease.

A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

“…These observations are recapitulated by many experimental models of disease, where the development of podocyte injury due to toxins or immune stimuli depends on the use of specific strains or species (4). These data, together with the finding of increased familial aggregation in humans (5), suggest that genetic predisposition is an important requirement for expression of secondary nephropathies. Genetic and environmental components can be best studied in animal models, where they can be more easily controlled and distinguished.…”

“…Genetic factors are implicated in the development of nephropathy and susceptibility to cytotoxicity induced by chemotherapeutic agents (5,22,23). Both of these traits are generally considered to have multifactorial determination, complicating efforts to distinguish contributions of single genes.…”

Genetic Factors in Diabetic Nephropathy

“…In the largest analysis to date, nearly 26,000 incident US dialysis patients from more than 450 dialysis clinics were screened for family history of ESRD (6). Individuals with known genetic disorders (e.g., autosomal dominant polycystic kidney disease, hereditary nephritis) and urologic disorders (surgical nephrectomy) were excluded.…”

Generalization of Associations of Kidney-Related Genetic Loci to American Indians

“…Of interest is the high proportion of the interindividual variation in eGFR explained by the SNPs in the five associated loci (2.2%), which corresponds to 2.9% of heritability of eGFR in our pedigrees. This finding is in contrast to the discovery population studies, in which 16 validated SNPs explain only eGFR and LUACR residuals were obtained from linear regression models adjusted for age, age 2 , sex, and age-by-sex interactions (Materials and Methods).…”