Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes

Abstract

Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.

Keywords: Biomarkers; Diabetes; Diabetic kidney disease; Glomerular disease; Kidney biopsy; Nondiabetic kidney disease; Sodium-glucose cotransporter-2 inhibitors.

Figure 1

Pure diabetic glomerulopathy. A: The glomerulus shows nodular expansion of the mesangial matrix and segmental sclerosis with hyalinosis (H&E 40 ×); B: Nodular mesangial matrix expansion with peripheralized capillaries (Jones methenamine silver 40 ×).

Figure 2

Nondiabetic kidney disease. A: Membranoproliferative glomerulonephritis and diabetic nephropathy. Lobulated glomerulus due to nodular mesangial expansion and endocapillary hypercellularity in a patient with diabetes and proliferative glomerulopathy with monoclonal immunoglobulin deposition (PAS 40 ×); B: Severe effacement of the foot processes over thickened glomerular basement membranes in a patient with diabetic glomerulosclerosis with superimposed podocyte injury (electron microscopy, magnification 2000 ×).