Impact of SGLT-2 Inhibitors on Aggregate Index of Systemic Inflammation in Patients with Stage 3-4 Chronic Kidney Disease: A Retrospective Cohort Study

SGLT-2 Inhibitors and AISI in CKD

Abstract

Background: Chronic kidney disease (CKD) is characterized by systemic inflammation that contributes to cardiovascular morbidity. The Aggregate Index of Systemic Inflammation (AISI), calculated as (neutrophils × platelets × monocytes)/lymphocytes, has emerged as a prognostic biomarker. SGLT-2 inhibitors demonstrate anti-inflammatory properties in CKD, yet their impact on AISI remains unexplored. We aim to evaluate the impact of SGLT-2 inhibitor therapy on AISI values in patients with stage 3-4 CKD and type 2 diabetes mellitus.
Methods: This retrospective cohort study included 148 patients with stage 3-4 CKD and type 2 diabetes mellitus who initiated SGLT-2 inhibitor therapy at Gazi University Nephrology Clinic between September 2024 and September 2025. AISI was calculated from complete blood counts at baseline and follow-up (mean 48.0 ± 12.2 days). The primary outcome was change in AISI values. Paired t-test was used for statistical analysis.
Results: Mean age was 67.15 ± 9.20 years, 54.7% were male, and baseline eGFR was 38.9 ± 12.1 mL/min/1.73m². Patients received empagliflozin (n=74) or dapagliflozin (n=74). AISI showed no significant change from baseline to follow-up indicating no significant difference (519.89 ± 319.52 vs. 503.15 ± 442.39, p=0.535).
Conclusions: SGLT-2 inhibitor therapy does not significantly alter AISI values in stage 3-4 CKD patients with diabetes over short-term follow-up. The established cardiovascular and renal benefits of SGLT-2 inhibitors appear to operate through mechanisms not reflected in this composite inflammatory marker.