Diabetic kidney disease (DKD) is a significant contributor to the development of end-stage renal disease and cardiovascular disease (CVD), with inflammation being a critical factor in its pathogenesis. The aim of this study is to examine the relationship between the neutrophil-to-lymphocyte ratio (NLR), a new inflammatory marker, and mortality from all causes and CVD in patients with DKD.This multicenter, retrospective cohort study utilized data from the China Renal Data System (CRDS) on patients with DKD hospitalized between January 1, 2000, and February 28, 2023. The patients' demographic information, along with their initial clinical and laboratory results, were collected and recorded. Follow-up continued until July 1, 2023, and patients were categorized into two groups based on the median baseline NLR. The Cox proportional hazards regression, Restricted cubic spline (RCS) curves, The Kaplan-Meier curve, Fine-Gray competing risk model, Time-dependent ROC and subgroup analysis were used to analyze the association between all-cause mortality and CVD mortality in patients having DKD with varying NLR.This study included 11,427 patients who had been clinically diagnosed with DKD. Baseline NLR was associated with C-reactive protein, procalcitonin, high-sensitivity C-reactive protein, plasma D-dimer, cystatin C, creatinine, urea nitrogen, brain natriuretic peptide, and eGFR. We selected the demographic characteristics, differential factors from univariate analysis, and clinically DKD-related laboratory indicators as covariates for Cox analysis. Results indicated that NLR was an independent risk factor for both all-cause and CVD mortality after adjusting for the relevant variables. The risk of all-cause death and CVD death in the high NLR group was 4.688 and 2.141 times higher, respectively, compared to the low NLR group (HR = 4.688, 95% CI 1.153-19.061, P = 0.031; HR = 2.141, 95% CI 1.257-3.644, P = 0.005). However, potential confounding factors and biases, such as unmeasured variables and the influence of treatment interventions, could not be fully accounted for.NLR can independently predict the risk of all-cause and CVD mortality in patients with DKD. Identifying individuals with a high NLR and providing further intervention could be crucial measures to reduce both all-cause and CVD mortality. However, the results should be interpreted with caution due to the study's limitations.© 2024 Bai et al.