Genetic susceptibility to end-stage renal disease

New methods have been developed to uncover the genotypes that result in com plex diseases. End-stage renal disease is a complex disease, without a simp le correspondence between genotype and phenotype. Both population-based and family-based epidemiological studies and analysis of model organisms sugge st that the pathogenesis of end-stage renal disease may have a genetic comp onent. A number of studies have analyzed candidate nephropathy genes with l ittle success, but recently several well-designed studies of multiplex fami lies with diabetic nephropathy have identified candidate nephropathy suscep tibility loci. To date, kidney disease-oriented research has focused on eff ector mechanisms responsible for the initiation and progression of chronic renal disease. However, because end-stage renal disease is a complex diseas e, interruption of a single effector pathway is unlikely to result in signi ficant therapeutic benefit. Further understanding of the pathogenesis of ki dney disease and the development of new kidney disease therapies will requi re continued application of genetic and genomic tools to kidney disease res earch. Curr Opin Nephrol Hypertens 8:465-472. (C) 1999 Lippincott Williams & Wilkins.