Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus Before and After Availability of Direct Acting Antiviral Therapy

Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods: Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by Chi-square and Fisher's exact tests. Results: The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA vs post-DAA (8% v 1%, p=0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) vs pre-DAA (1.3%) (p< 0.0001). Post-DAA there were less MPGN (2% vs 10%, p=0.02) and more advanced DGS (85% v 61%, p=0.0002), non-collapsing FSGS (57% v 31%, p<0.0001), IFTA (2.0 v 1.6, p=0.0002), and vascular sclerosis (2.1 v 1.6, p<0.0001). Conclusion: Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.