Inflammation, Body Mass Index, and Cardiovascular Outcomes in Chronic Kidney Disease and Type 2 Diabetes

Introduction and Objective: Inflammation is a key driver of residual cardiovascular (CV) risk in persons with chronic kidney disease (CKD), but the extent to which it is associated with obesity in this population is underexplored.Methods: In this participant-level pooled analysis of the FIDELITY program, the association between high-sensitivity C-reactive protein (hsCRP) and body mass index (BMI) was examined among adults with CKD and type 2 diabetes (T2D). The association between hsCRP, overall and by BMI, and CV outcomes was also assessed.Results: Among 12,864 participants (mean age, 65 ± 10 years; 30 median hsCRP, 2.2 [1.0, 5.1] mg/L), 53≥2 mg/L) at baseline. The covariate-adjusted odds of an elevated baseline hsCRP increased steeply with higher baseline BMI (Figure 1A). Higher baseline hsCRP levels were incrementally associated with a higher rate of composite CV events (aHR per hsCRP doubling, 1.11; 95 1.07-1.14). However, these risks were primarily observed among persons with elevated BMI (Pinteraction=0.002) (Figure 1B). Benefits of finerenone on the composite CV outcome were consistent irrespective of baseline hsCRP (Pinteraction=0.21) and BMI (Pinteraction=0.43).Conclusion: Low-grade inflammation is highly prevalent and linked with adverse risks of clinical events in persons with CKD and T2D, particularly those with BMI-defined overweight or obesity. Benefits of finerenone were not modified by baseline BMI or hsCRP.J. Ostrominski: Advisory Panel; Current; Corcept Therapeutics. G. Filippatos: Other - lecture fees and /or advisory and /or trial committee membership; Current; Bayer AG, Boehringer Ingelheim International GmbH. Other - lecture fees and /or advisory and /or trial committee membership; Ended; Servier Laboratories, Novartis AG. Other - lecture fees and /or advisory and /or trial committee membership; Current; Impulse Dynamics. Other - lecture fees and /or advisory and /or trial committee membership; Ended; Vifor Pharma Management Ltd. Other - lecture fees and /or advisory and /or trial committee membership; Current; Medtronic, Novo Nordisk, Cardior Pharmaceuticals GmbH. Other - lecture fees and /or advisory and /or trial committee membership; Ended; MDS Co., Ltd. Research Support; Current; European Union. P. Rossing: Advisory Panel; Ended; Abbott Diagnostics. Advisory Panel; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Eli Lilly and Company. Consultant; Current; Lexicon Pharmaceuticals, Inc., Roche Pharmaceuticals. Consultant; Ended; Amgen Inc. M. Brinker: Employee; Current; Bayer AG. Other - pending patent for finerenone for treatment of patients with CKD and T1D; Current; Bayer AG. Stock/Shareholder; Current; Bayer AG. P. Schloemer: Employee; Current; Bayer AG. A. Glasauer: Employee; Current; Bayer AG. S.D. Solomon: Research Support; Current; Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cardior, Cytokinetics, Edgewise, BridgeBio, Gossamer, GSK, Ionis, Lilly, NIH/NHLBI, Novartis, NovoNordis. Consultant; Current; Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, Askbio, AstraZeneca, Bayer, BMS, Bridgebio, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantu. M. Vaduganathan: Other - research grant support, served on advisory boards, or had speaker engagements; Current; Alnylam Pharmaceuticals, American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia Pharmaceuticals, L, Novartis, Novo Nordisk, Pharmacosmos, Recordati, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Research Support; Current; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Galmed, Impulse Dynamics, Novartis, Occlutech, and Pharmacosmos. A.Z. Lage: None.