Traditional and proteomic biomarkers of autosomal dominant polycystic kidney disease (ADPKD)

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary renal disease, is characterized by continuous and progressive growth of innumerable cysts in both kidneys. Despite gross enlargement of the kidneys, renal function is usually maintained within the normal range for decades through hyperfiltration of the remaining nephrons. Once renal function starts to decline, it usually deteriorates rapidly resulting in end-stage renal disease (ESRD) within a few years. Until recently, the treatment of ADPKD has been exclusively symptomatic, but based on accumulating mechanistic insights, several potential targeted pharmacological therapeutic approaches have now been emerging during the last decade. This development has led to an urgent need for biomarkers to allow early detection of patients at risk for accelerated progression and as surrogate markers for interventional trials. Total kidney volume (TKV) assessed by magnetic resonance imaging (MRI) or computed tomography (CT) is the most extensively studied measure of disease severity and correlates with future renal function loss. In addition, a few biochemical markers as well as proteomic and metabolomic patterns have been described that characterize patients with ADPKD. While some of these markers are promising, their use to reliably predict prognosis has yet to be proven. A major obstacle to the discovery and validation of biomarkers for ADPKD is the slowly progressive nature of the disease and the still limited follow-up information on well-characterized patient cohorts. As longitudinal information on well-characterized patients continues to accumulate, the discovery and validation of disease progression markers will be greatly facilitated. This chapter summarizes both established progression markers of ADPKD (i.e., kidney and cyst volume) and recently used approaches to the discovery of novel biochemical markers and discusses general aspects relevant to biomarker discovery for ADPKD.