ESKD, Major Cardiovascular Events, and Death Associated With Systemic Inflammation

Introduction Systemic inflammation may play a role in the progression of chronic kidney disease (CKD) and in the development of major cardiovascular events (MACE). Whether this effect is independent of traditional cardiovascular risks is unclear. Methods In this study, we compared the incidence of end-stage kidney disease (ESKD) (i.e., chronic dialysis or renal transplantation), MACE, and death in patients with CKD with high sensitivity C-reactive protein (hsCRP) ≥ 2 mg/l versus hsCRP < 2 mg/l, using the TRINETX platform. Results Overall, 163,854 subjects with CKD (defined as estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m 2 , Kidney Disease: Improving Global Outcomes [KDIGO] CKD 3–4) or albumin-to-creatinine ratio > 200 mg/g) (KDIGO A3), hsCRP results, and no concomitant infection were included. After propensity score matching, 27,580 patients with hsCRP ≥ 2 mg/l were compared with 27,580 subjects with hsCRP < 2 mg/l, well-matched for traditional cardiovascular risk factors, including blood pressure, low-density lipoprotein (LDL) cholesterol, baseline treatments, eGFR, and albuminuria. hsCRP ≥ 2 mg/l was associated with a higher risk of MACE (ischemic stroke, myocardial infarction, heart failure, and atrial and ventricular fibrillation) and death (hazard ratio [HR]: 1.941 [95% confidence interval [CI]: 1.853–2.032]) but not a higher risk of ESKD (HR: 1.271 [0.893–1.809]) versus hsCRP < 2 mg/l during follow-up. Among patients with diabetes (21,700 patients), hsCRP ≥ 2 mg/l was associated with higher risks of MACE and death as well as with a higher risk of ESKD (HR: 1.508 [0.997–2.281], P = 0.05). Conclusion Systemic inflammation is associated with a higher risk of MACE and death among subjects with CKD 3 and 4 or albuminuria (A3), and a higher risk of ESKD among patients with diabetes mellitus, independently of traditional risk factors.