The Corticotropin Releasing Factor System in the Kidney: Perspectives for Novel Therapeutic Intervention in Nephrology

The adaptation to endogenous and exogenous stress stimuli is crucial for survival but also for the onset of various diseases in humans. Corticotropin releasing factor (CRF) system is the major regulator of stress response and homeostasis. The members of this family of peptides extend their actions also outside CNS to the periphery where they may affect various body systems independently, acting via vagal and/or autocrine/paracrine pathways. In search for peripheral targets, kidney has rarely been studied separately, regarding expression and action of CRF and CRF-related peptides. We reviewed the existing literature concerning expression and action of the CRF system in normal and pathological renal tissue and explored possible clinical implications in nephrology. CRF system components are expressed in the kidney of experimental animals and in humans. The intrarenal distribution is reported to be equally extensive, suggesting a physiological or pathophysiological role in renal function and in the occurrence of renal disease. Urocortins have given multiple interesting observations in experimental models of renal disease and clinical studies, showing robust effects in renal regulation mechanisms. We summarize the relevant data and put them in context, proposing applications with clinical significance in the field of hypertension, diabetic nephropathy, chronic kidney disease, cardiorenal syndrome, and peritoneal dialysis.