Clinical Trials in Renal Regenerative Medicine

Kidney disease is a growing global public health issue. Chronic kidney disease (CKD) has a prevalence of over 10% in the general population and this number is increasing by almost 3% per year. Advanced CKD is associated with a more than three-fold increased risk for cardiovascular events and an almost six times increased mortality. Acute kidney injury (AKI) is also an increasing clinical problem, with an incidence of 15 patients per 1000 patient years (Medicare database). Mortality rates of AKI are up to 80% and more than 10% of the survivors eventually develop end-stage renal disease (ESRD). More than 350 new cases of ESRD per 1,000,000 population are seen every year, according to the United States Renal Data System (USRDS) 2009 annual data report. Therapeutic strategies for kidney disease have focused on the reduction of tissue damage and supportive care. Prognostic assessment of the outcome of renal disease is important to guide clinical decisions. To adequately predict renal outcome, which can be envisioned as the balance between renal damage and renal repair, both detrimental processes and (potential) regenerative capacity should be quantified. Clinical trials correlate a certain prognostic or therapeutic intervention with an outcome parameter, which can cover the complete spectrum from histology to mortality. However, the number of preclinical data on therapeutically enhanced regeneration in models of diabetes induced renal failure is limited. In contrast, numerous preclinical studies have investigated therapeutically enhanced regeneration in acute tubular damage models, both toxic and ischemic.