Elevated Serum LL37 and MPO-DNA Complexes Predict the Progression of Diabetic Kidney Disease

Background: Predicting early progression of diabetic kidney disease (DKD) remains challenging. The neutrophil-derived peptide LL37 is implicated in kidney inflammation, yet its role and prognostic value in DKD remains unclear. Methods: RNA sequencing dataset was analyzed to examine the expression of CAMP (encoding LL37) and myeloperoxidase (MPO) in peripheral blood from diabetic mellitus patients. A clinical cohort of 94 biopsy-proven DKD patients and 63 healthy controls (HC) was established. Serum LL37 and MPO-DNA complexes were measured using enzyme-linked immunosorbent assay. The correlation between serum LL37 and MPO-DNA complex levels and kidney function was assessed, and assessed their association with DKD progression using restricted cubic spline analysis and Cox proportional hazards regression models. Results: Bioinformatics analysis revealed significantly elevated CAMP expression in DM patients, with strong neutrophil infiltration. In the clinical cohort, serum LL37 levels were significantly higher in DKD patients than in HC, showing discriminatory power for DKD diagnosis (AUC=0.90, 95%CI: 0.85-0.96). Serum LL37 and MPO-DNA complex levels correlate with elevated serum creatinine and reduced eGFR. After a median follow-up of 39 months, 60 patients (63.83%) experienced renal progression events. After adjusting for confounding factors, elevated serum LL37 and MPO-DNA complex levels were independent risk factors for DKD progression [per Ln-transformed HRs: 2.290 (95% CI: 1.491-3.518) and 1.833 (95% CI: 1.261-2.664), respectively]. Conclusion: Elevated serum LL37 and MPO-DNA complex levels are independently associated with kidney disease progression in patients with DKD, and increased circulating LL37 may be closely linked to neutrophil activation.