Fast renal decline to ESRD: an unrecognized feature of nephropathy in diabetes

Abstract

A new model of diabetic nephropathy in T1D emerged from our studies of Joslin Clinic patients. The dominant feature is progressive renal decline, not albuminuria. This decline is a unidirectional process commencing while patients have normal renal function and, in the majority, progresses steadily (linearly) to ESRD. While an individual’s rate of renal decline is constant, the eGFR slope varies widely among individuals from −72 to −3.0 ml/min/year. KDIGO guidelines define rapid progression as rate of eGFR decline <−5 ml/min/year, a value exceeded by 80% of patients in Joslin’s T1D ESRD cohort. The extraordinary range of slopes within the rapid progression category prompted us to partition it into “very fast”, “fast” and “moderate” decline. We showed for the first time that very fast and fast decline from normal eGFR to ESRD within 2–10 years constitutes 50% of the Joslin cohort. In this review we present data about frequency of fast decliners in both diabetes types, survey some mechanisms underlying fast renal decline, discuss methods of identifying patients at risk and comment on the need for effective therapeutic interventions.

Whether the initiating mechanism of fast renal decline affects glomerulus, tubule, interstitium or vasculature is unknown. Since no animal model mimics progressive renal decline, studies in humans are needed. Prospective studies searching for markers predictive of the rate of renal decline yield findings that may make detection of fast decliners feasible. Recognizing such patients will be the foundation for developing effective personalized methods to prevent or delay onset of ESRD in diabetes.