Rapid Progression of Diabetic Nephropathy Is Linked to Inflammation and Episodes of Acute Renal Failure

Abstract

Background/Aims: Chronic kidney disease (CKD) from diabetic nephropathy is characterized by progressive loss of renal function. The renal decline has been viewed as a linear fall, presumably dependent on metabolic, hemodynamic and dietary stresses. However, renal injury in diabetic nephropathy can be rapidly aggravated by unpredictable external and internal factors, a state of affairs inconsistent with a linear loss of function. Acute renal injury and subsequent inflammation are potential factors, and we investigated their presence in renal biopsies from patients with nephropathy. Methods: In a protocol approved by the Indiana University School of Medicine Institutional Review Board, renal biopsy specimens, estimated GFR, proteinuria and renal survival were examined in patients with diabetic nephropathy. Results: Prominent clusters of inflammatory cells, particularly macrophages, were detected in the renal biopsy specimens. CKD progressed rapidly but not linearly, in that CKD was characterized by a succession of seemingly random episodes of self-limited acute renal failure. Episodes of acute kidney injury were associated with progression to end-stage renal disease. Conclusions: We propose that diabetic nephropathy is complicated by unpredictable and possibly random episodes of usually self-limited acute renal failure, and by subsequent renal inflammation, which appear to accelerate progression and eventual kidney loss.