High levels of the inflammatory mediator interleukin-6 (IL-6) may lead to diabetic kidney disease (DKD) progression, investigators reported at the 58th European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress.
Of 70 patients with type 2 diabetes, stage 2 or 3 chronic kidney disease, and a urinary protein to creatinine ratio (UPCR) of more than 300 mg/g in the PRONEDI trial, 27 patients experienced the study’s primary endpoint, which was a composite of a greatere than 50% increase in baseline serum creatinine, end-stage kidney disease (ESKD), or death. Mean survival was 33.2 months.
From baseline to 12 months, mean IL-6 levels increased in the cohort from 4.58 to 6.14 pg/mL. Patients with the highest tertile of IL-6 (more than 4.84 pg/mL) experienced significantly faster progression to the primary composite endpoint compared with patients in the lower tertiles, Beatriz Sanchez Alamo, MD, of Hospital Universitario Fundación Alcorcón in Spain, and colleagues reported. This group had a significant 3.9-fold increased risk for the primary composite endpoint after adjustment for baseline serum creatinine and proteinuria. The best threshold IL-6 level for predicting DKD progression was 4.68 pg/mL (sensitivity: 100%, specificity: 78.7%).
Use of optimal doses of renin-angiotensin system (RAS) blockade as monotherapy or dual therapy did not lower IL-6 levels, the investigators noted.
“Serum IL-6 may be used as a noninvasive biomarker of progression to ESKD,” according to Dr Alamo’s team. “Since our results show that higher IL-6 levels are associated with a worse renal prognosis, anti-inflammatory drugs that modulate IL-6 could be promising therapeutic agents to improve outcomes.”
Ziltivekimab, a novel IL-6 ligand monoclonal antibody, was recently shown to reduce inflammation in patients with chronic kidney disease (CKD) and atherosclerosis. More than two-thirds of patients in that trial (Lancet; 397:2060-2069) had diabetes.
“Further studies focusing on the potential applications of anti-IL6 treatment in DKD are warranted,” Dr Alamo’s team stated.
Sanchez Alamo B, Shabaka A, Cachofeiro Ramos M, Fernandez Juarez GM. Serum interleukin-6 levels predict renal disease progression in diabetic kidney disease. Presented at the ERA-EDTA Congress 2021, June 5-8, 2021. Abstract FC085.
Ridker PM, Devalaraja M, Baeres FM, et al. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. Published online May 17, 2021. doi:10.1016/S0140-6736(21)00520-1