A case of diabetic nephropathy with mesangial matrix dissolution and long-term use of a dipeptidyl peptidase-4 inhibitor

A 46-year-old man was administered the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (5 mg/day) for type 2 diabetes mellitus. His hemoglobin A1c level subsequently stabilized at less than 7.0%, but 10 years later, his renal function deteriorated markedly. His serum creatinine level was 2.82 mg/dL, and urinary protein level 8.26 g/g creatinine. A kidney biopsy was performed. Light microscopy revealed diabetic nephropathy with Kimmelstiel-Wilson nodular lesions, but also endocapillary hypercellularity and mesangiolysis with severe edematous expansion of the mesangial area, leading to a diagnosis of thrombotic microangiopathy-like glomerular microangiopathy (GMA). Electron microscopy also showed widespread loss of mesangial cells and matrix, with only endothelial cell nuclei and the glomerular basement membrane thickening remaining. While cases of mesangiolysis and endothelial cell proliferation associated with DPP-4 inhibitors have been reported, we present a case demonstrating severe mesangiolysis in a patient who had progressed to develop nodular lesions.