Non-Classical Clinical Types and Pathological Changes of Diabetic Kidney Disease: A Review

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD. A typical early clinical manifestation of DKD is microalbuminuria and patients may present with macroproteinuria accompanied by a decrease in renal function condition as the disease progresses. It is generally believed that the likelihood of a reversal of the disease is reduced after the development of macroproteinuria in patients with DKD, and that eventually some patients' condition may develop into end-stage renal disease (ESRD). Moreover, the thickening of the glomerular basement membrane, mesangial matrix expansion, Kimmelstiel-Wilson (K-W) nodules, and glomerulosclerosis in end-stage diabetes mellitus are typical pathologic changes of DKD. However, some DKD patients, especially those with type 2 diabetes mellitus (T2DM) combined with chronic kidney disease, may have diverse clinical manifestations, showing variations in disease progression and regression, and manifesting as non-classical types of DKD, such as normoalbuminuric DKD, proteinuria-reduced DKD, and DKD with rapid decline in renal function. In addition, the formation of crescents, a special pathological change, is observed in renal biopsy. However, this issue is currently under-recognized by clinicians and therefore deserves more attention. In order to improve clinicians' understanding of the presentations and pathological changes of non-classical DKD and the level of DKD prevention and treatment in China, we present a preliminary introduction to the clinical phenotypes and pathological changes of non-classical types of DKD in this paper by summarizing the findings of our prior studies as well as domestic and international literature.