Impact of Diabetic Lesions on Pathology, Treatment and Outcomes of Glomerular Diseases.

Abstract

We aimed to evaluate whether concomitant diabetic glomerulosclerosis (DGS) and its severity impact the treatment and outcomes of primary glomerular diseases (GD) with comorbid diabetes. We conducted a retrospective review of people with diabetes and GD. We searched the Glomerular Disease Collaborative Network for biopsies from 2008 to 2015 among persons with diabetes and any of the following diagnoses: Focal Segmental Glomerulosclerosis (FSGS), IgA Nephropathy (IgAN), Minimal Change Disease (MCD), Membranous Nephropathy (MN) or Anti-Neutrophil Cytoplasmic Autoantibody Glomerulonephritis (ANCA GN). Data were abstracted from health records and histologic diabetic glomerular class scored. The primary composite endpoint was end-stage kidney disease (ESKD) or death. Multivariable Cox regression models tested whether any or the severity of diabetes histopathology impacted the primary endpoint. Data from 134 cases were available for analysis (78 DGS+GD and 56 GD alone). Diabetes duration and glycemic control were similar between the two groups (p=0.2; p=0.09, respectively). Use of immunosuppression did not differ between the two groups (p=0.3). The composite endpoint was significantly higher in DGS+GD [22.5 cases per 100 p-y (95% CI: 16.6-30.5)] versus GD alone [10.2 cases per 100 p-y (95% CI: 6.4-16.2)]. Regression analyses demonstrated that compared to the GD alone group, the risk for the composite endpoint was similar in the group with mild DGS+GD (DGS class 1, 2a) [HR=1.15 (95% C: 0.54-2.43)], while the group with severe DGS+GD (DGS class 2b, 3, 4) had a greater risk [HR=3.60 (1.79-7.22)]. Among people with diabetes and GD, mild diabetic glomerular lesions on biopsy do not impact outcomes, but moderate-severe lesions increase the risk for ESKD and death. Whether use of immunosuppression, particularly glucocorticoids, is less successful in inducing GD remission in people with moderate-severe diabetic lesions will be a focus of future study in a larger population.