Genetic basis of nondiabetic end-stage renal disease

Recent breakthroughs in genomics have led to a critical reappraisal of factors once thought to initiate common complex forms of kidney disease. The tenet that diabetes mellitus and hypertension routinely initiate kidney disease whenever blood glucose concentrations or systemic blood pressures reach critical levels for prolonged periods is falling from favor, although it remains important to control hypertension and hyperglycemia to slow nephropathy progression and to prevent cardiovascular disease. Many patients with systemic diseases that potentially may involve their kidneys never develop nephropathy. In addition, severe forms of several common kidney diseases cluster tightly in families. This article discusses the existence of differential nephropathy susceptibility based on an individual's genetic make-up, in the context of environmental exposures. Novel genetic analysis methods and recently identified major kidney disease susceptibility genes are discussed, including novel perspectives for categorizing complex forms of nephropathy based on the expanding spectrum of non-muscle myosin heavy chain 9 gene-associated disease. Genetic screening, gene-environment, and gene-gene interactions are also addressed.