#2969 IS DIABETES MELLITUS ASSOCIATED WITH WORSE KIDNEY OUTCOME IN PATIENTS WITH GLOMERULOPATHIES?
Authors: Ciurea Otilia , Capusa Cristina-Stela , Petre Nicoleta , Mandache Eugen , Mircescu Gabriel 
Published: June 2023

Abstract

Background and Aims
Diabetes mellitus (DM) is the leading cause of end stage kidney disease and a major risk factor for cardio-vascular disease and death. While it is known that subjects with diabetic nephropathy (DN) have a worse kidney outcome compared to other non-diabetic glomerulopathies, it is not certain whether DM independently influences the kidney outcome in subjects diagnosed with glomerulopathies (GP) other than diabetic nephropathy.

Method
This retrospective study included 1200 adults [50 (95%CI 48 to 51) years, 56% males, eGFR 48.5 (95%CI 45.9 to 51.3) mL/min], with kidney biopsy (KB) proven GP between 1st Jan. 2008 and 31st Dec. 2017. Subjects were followed for a mean of 89 (95%CI 85.5 to 92.4) months until 31st May 2018. The primary endpoints were the initiation of chronic renal replacement therapy (RRT) or death. Subjects with inappropriate biopsy sample, insufficient data and RRT prior to KB were excluded. Demographic, clinical and laboratory data at the time of biopsy were retrieved from medical records. Kidney survival was evaluated by Kaplan-Meier method and a competitive risk to event analysis was used to estimate the risk of RRT, considering death as a competing event. Variables related to kidney outcome were evaluated by the subdistribution hazard function using Fine-Gray model. According to the presence or absence of DM and the types of GP, subjects were divided in three groups: GP without DM (n = 987 pts.), GP with DM (n = 65 pts.), and DN (n = 148 pts.).

Results
GP with DM subjects were older (60 (95%CI 56 to 64) years vs. 55.5 (95%CI 54 to 59) years in DN group vs. 47 (95%CI 45 to 48) years in GP without DM; p&lt;0.001). Males were predominant in all groups, with higher frequency in DN group (66.9% vs. 54.9% - GP without DM vs. 61.5% - GP with DM; p = 0.01). DN group had higher Charlson comorbidity index [5 (95%CI 4 to 5) vs. 2 (95%CI 2 to 2) in GP without DM vs. 3 (95%CI 3 to 4) in GP with DM; p&lt;0.001], lower eGFR (31.3 (95%CI 25.4 to 36.7)mL/min vs. 51.9 (95%CI 48.9 to 55.8)mL/min in GP without DM vs. 43.2 (95%CI 35.4 to 51.3) mL/min in GP with DM; p&lt;0.001) and higher proteinuria (4.9 (95%CI 3.8 to 6) g/g vs. 2.6 (95%CI 2.35 to 2.9) g/g in GP without DM vs. 4.3 (95%CI 2.7 to 6.7) g/g in GP with DM); p&lt;0.001]. During the follow-up period, 24.3% needed RRT, while 11.4% died. The highest RRT initiation and death frequency was in DN group (40.5% vs. 21.7% in GP without DM vs. 27.7% in GP with DM; p&lt;0.001, and 18.2% vs. 10% in GP without DM vs. 19.9% in GP with DM; p = 0.004). In the univariate time-dependent analysis, subjects with DN had the worse kidney outcome (log rank p&lt;0.001) (Fig. 1), however the kidney survival was similar between GP with DM and GP without DM subjects (log rank p = 0.1). In the competitive risk time to event analysis where death is considered the competing event, diabetic nephropathy subjects had worse kidney survival than GP with DM subjects [CIF 2.3 vs. 1.3, p&lt;0.001], while GP with DM had similar survival with GP without DM (CIF 1,3; p = 0.2) (Fig. 2). After adjusting for the risk factors for CKD progression, DM was not associated with an increased risk of RRT (HR = 0.98, p = 0.9). Predictors for RRT were diabetic nephropathy on KB, along with younger age, lower serum albumin, and lower baseline eGFR.

Conclusion
In this large cohort of subjects with glomerulopathies, diabetes mellitus complicated with diabetic nephropathy seem to have a worse kidney outcome, while DM in subjects with glomerulopathies other than DN doesn't seem to influence the progression to RRT.