Molecular approaches to chronic kidney disease

Abstract

The progression of chronic kidney disease to terminal renal failure remains a major challenge in nephrology. Definition of the dynamic differences in gene regulation, protein interaction and protein function in this process might allow the development of rationally designed management strategies for the individual patient. Current approaches to identifying the molecular markers required to implement this 'personalized medicine' concept in progressive renal failure will be presented in this review. In small populations, molecular fingerprints derived from renal biopsies have allowed the definition of distinct patient subgroups. These parameters could be shown to correlate with the response to available therapies and, in chronic transplant failure, with the therapeutic toxicity of cyclosporine. Urine analysis for mRNA and protein markers is rapidly evolving as a non-invasive approach for molecular patient monitoring. As only a small fraction of these fingerprints have been evaluated in independent populations, studies to test marker sets in diverse cohorts for their clinical applicability are warranted. The genome-wide tools discussed in this review might define the molecular mechanism active in each single patient with progressive kidney disease. Reflecting the individuality of the disease process could result in a tailored therapy for the unique human being, contrasting with the 'one-size-fits-all' therapies currently employed in nephrology.