Genetic factors in progressive renal disease: the good ones, the bad ones and the ugly ducklings.

Worldwide, >1 million people have developed endstage renal disease (ESRD) and need renal replacement therapy. ESRD is secondary to a broad range of diseases that include diabetic nephropathy and focal and segmental glomerulosclerosis. The rate of progression to ESRD varies among patients suffering from kidney diseases, and is to a large extent determined by genetic factors. We will discuss studies that have provided evidence for a genetic component underlying susceptibility to progressive renal disease. On the one hand, gene mutations may result in a disturbed function of the corresponding protein, which will lead directly to kidney disease. On the other hand, genetic factors may become manifest only in the presence of systemic diseases, such as hypertension and diabetes mellitus, and thus modify the outcome of the kidney disease. For instance, polymorphisms in genes encoding proteins that are able to protect the renal tissue against permanent damage may be the basis of differences in susceptibility to disease progression among patients. Identification of novel genetic factors determining renal disease susceptibility may increase the understanding of the pathogenesis of ESRD. The regenerative effects of endogenous molecules in the kidney may be exploited to counteract the growing incidence of ESRD efficiently.