Biomarkers of diabetic nephropathy, the present and the future

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Searching for the perfect biomarker of DN has become the holy grail of nephrology since the burden of this disease is untenable. The only feasible way to tackle this health care crisis is by prevention and treatment in a mechanistically rational approach. Therefore, the discovery of a specific, reliable diagnostic and prognostic biomarker for DN is imperative. Part of the difficulty in finding such a marker is the complex pathogenesis of DN; it is clearly multifactorial and involves multiple genes, proteins, metabolic pathways, and environmental factors. In this review, we will discuss the latest findings in the use of genetic, protein, and metabolic markers of DN. Particular attention will be paid to the urinary biomarker as a noninvasive method to detect either morphological or biochemical changes in DN. Urinary protein and mRNA studies have focused on either the glomerular (podocyte-specific) or tubular components (matrix or injury-related) of the nephron. The virtues and pitfalls of using the podocyte as a biomarker will be discussed. The systems biology approach of biomarker discovery in the studies of genomics, transcriptomics, proteomics, and metabolomics will be explored. Despite significant numbers of new biomarkers described, most studies are limited by either their small sample size or their cross-sectional nature, so that the ability to predict future and severity of DN is lacking. In order to successfully search for the ideal, validated biomarker, we need to conduct large, prospective, multi-center trials enlisting both Type 1 and Type II diabetic patients with and without nephropathy for at least two decades.