Diabetic Kidney Disease: Past and Present

Diabetes mellitus (DM) afflicting humans has been recognized as a disease for >3000 years. However, very little was known about its etiology and pathogenesis until about a century ago when increasing knowledge about anatomy and physiology of the human body gradually led to our understanding that the hormone insulin produced by the Islets of Langerhans in the pancreas plays a crucial role in the metabolism of glucose and maintaining the blood sugar level within a normal range. DM is caused by inadequate insulin production (type 1) or insulin resistance (type 2). For thousands of years, DM has been considered as a disease of the kidney; however, with the understanding of the pathogenesis of DM, it became clear that diabetic kidney disease (DKD) is a complication and not a cause of DM. DKD is associated with increased matrix expansion that manifests morphologically as a diffuse or nodular expansion of the mesangium and diffuse thickening of the glomerular and tubular basement membranes. Hyperglycemia plays a crucial role in the development of pathologic changes within the kidney. Once established, DKD usually undergoes a slow but relentless progression to end-stage renal disease. However, recent studies have shown that its progression can be slowed or even reversed by strict control of hyperglycemia. Morphologically, DKD may resemble several other glomerular diseases that must be ruled out before a definitive diagnosis. Patients with DM may also develop nondiabetic glomerular or interstitial diseases with or without DKD. The findings in nephrectomy specimens and the differential diagnoses are presented in detail.