Searching for a genetic risk profile in end-stage renal disease

There is a strong evidence that both, genetic factors and environment, affect the development of end-stage renal disease (ESRD). The factors that initiate renal failure are probably different from those contributing to its progression. Some factors involved in the progression of nephropathy are already identified, like elevated blood pressure, hypercholesterolemia or hyperparathyroidism. Molecular genetic techniques are extensively applied to developing strategies for detection of human renal failure genes. The candidate gene approach for finding an association between polymorphic DNA markers and disease was successfully used in studying genes of the renin-angiotensin system, especially those coding angiotensin I-converting enzyme, angiotensinogen and angiotensin type 1 receptor. Several other genes, for example growth factors and cytokine genes, nitric oxide synthase or genes of the kallikrein-kinin system are being evaluated using this approach. Identification of candidate genes associated with end-stage renal disease will create a need for testing several disease loci simultaneously. Subsets of predictive genetic markers will be developed for routine use in clinical practice. Recognizing genetic changes affecting the initiation and progression of renal failure will have important clinical implications, involving testing individuals who are genetically susceptible but yet unaffected. It will make possible identification of individuals at a higher risk for renal failure and help in the choice of diagnostic tests as well as in planning therapeutic interventions.