A case report of dipeptidyl peptidase 4 inhibitor-related kidney disease combined with renal cancer

Abstract

A kidney biopsy was performed in a 64-year-old woman with type 2 diabetes mellitus and less than 1 g of proteinuria who rapidly progressed to end-stage renal failure after approximately 2 years of treatment with two dipeptidyl peptidase 4 (DPP-4) inhibitors for type 2 diabetes mellitus. The biopsy revealed not only a coincidental diagnosis of renal cell carcinoma, which was not evident on pre-biopsy computed tomography, but also severe thrombotic microangiopathy (TMA)-like glomerular endothelial cell damage in the noncancerous areas. These results suggest that DPP4 inhibitors may have been involved in two kidney diseases.

Keywords: dipeptidyl peptidase (DPP) 4 inhibitors; end-stage renal failure; kidney biopsy; renal cell carcinoma; thrombotic microangiopathy (TMA)-like lesion.

Figure 1

Clinical course. The figure shows the clinical course up to nephrectomy. The timing of kidney biopsy, hemodialysis and nephrectomy is indicated by thick arrows. Sitagliptin was given at Cre 1.2 mg/dL and was stopped when Cre fell to 2.2 mg/dL; alogliptin was started at Cre 3.0 mg/dL; hemodialysis was started when Cre reached 7.5 mg/dL.

Figure 2

Kidney biopsy and surgical specimen. (A, B) Tubulointerstitial fibrosis and tubular atrophy are observed in approximately 70% of the cortical area. (A) Masson trichrome staining. (B) Periodic acid–Schiff (PAS) staining. (C) Many of the preserved glomeruli show prominent fibrotic thickening (black arrow) of the glomerular basement membrane (GBM) of Bowman’s capsule and duplication (white arrow) of the GBM. Periodic acid methenamine silver and Masson staining. (D) Glomerular endothelial cell proliferation (arrow) was observed. PAS staining. (E) Immunofluorescence microscopy reveals linear fluorescence of immunoglobulin G (arrow) along the GBM, Bowman’s capsule, and tubular basement membrane. (F) Electron microscopy reveals endothelial cell proliferation (black arrow) with mesangiolysis (arrowhead) and subendothelial edema (white arrow). The GBM thickened to a width of 400–500 nm. (G) Two biopsy specimens showed clear cell renal cell carcinoma(arrow). Hematoxylin and eosin staining: original magnification ×200. (H) split section of the surgical specimen. A tumor(arrow), 9–10 mm in size, was found in the surgical specimen in the lower pole of the right kidney. (I) Histology also confirmed clear cell renal cell carcinoma(arrow). Hematoxylin and eosin staining; original magnification ×400.

Figure 3

Diagnostic imaging. (A) Computed tomography (CT) scan before contrast enhancement. (B) CT scan immediately after contrast enhancement; white arrow indicates hypervascular staining (Equivalent to renal cancer). (C) Magnetic resonance imaging; Black arrow indicates mass, 9 mm in size (Equivalent to renal cancer) in the lower pole of the right kidney. White arrow confirmed the presence of a right adrenal tumor.