Genetic susceptibility of hypertension-induced kidney disease

Hypertension is the second leading cause of end-stage renal disease (ESRD) after diabetes mellitus. The significant differences in the incidence of hypertensive ESRD between different patient populations worldwide and patients with and without family history indicate that genetic determinants play an important role in the onset and progression of this disease. Recent studies have identified genetic variants and pathways that may contribute to the alteration of renal function. Mechanisms involved include affecting renal hemodynamics (the myogenic and tubuloglomerular feedback responses); increasing the production of reactive oxygen species in the tubules; altering immune cell function; changing the number, structure, and function of podocytes that directly cause glomerular damage. Studies with hypertensive animal models using substitution mapping and gene knockout strategies have identified multiple candidate genes associated with the development of hypertension and subsequent renal injury. Genome-wide association studies have implicated genetic variants in UMOD, MYH9, APOL-1, SHROOM3, RAB38, and DAB2 have a higher risk for ESRD in hypertensive patients. These findings provide genetic evidence of potential novel targets for drug development and gene therapy to design individualized treatment of hypertension and related renal injury.