Higher Circulating Neutrophil Counts is Associated with Increased Risk of All-Cause Mortality and Cardiovascular Disease in Patients with Diabetic Kidney Disease

Background: Accumulating evidence has suggested the pathogenic roles of chronic inflammation and neutrophils in diabetic kidney disease (DKD). This study investigated the relationship between neutrophils, all-cause, and cardiovascular disease (CVD) mortality in type 2 diabetes mellitus (T2DM) patients with DKD. Methods: We used data from the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2020 to investigate the relationship between circulating neutrophils counts, kidney function indices, all-cause, and CVD mortality in adult T2DM patients with DKD. Clinical predictive models and risk scores for long-term mortality were constructed. Results: 44,332 patients [8034 with T2DM and 36,323 without T2DM] were included. Two thousand two hundred twenty patients had DKD, and 775 died (31.5% related to CVD) during a follow-up of 6.18 (range: 5.94–6.42) years. Higher neutrophil counts (Quartile 4, Q4) were associated with increased all-cause and CVD mortality [HR 1.73 (95% CI 1.34–2.25) and 1.81 (95% CI 1.14–2.89), respectively, p < 0.0001 and 0.01]. Neutrophil counts in Q4 showed a positive correlation with urine albumin-creatinine ratio (UACR) but a negative association with eGFR (p < 0.01 for all). Clinical predictive models incorporating neutrophil counts showed satisfactory performance in forecasting 5-year and 10-year CVD mortality-free survival (ROC AUC 0.824 and 0.842, respectively), and the nomogram-predicted survival demonstrated good concordance with observed survival. Conclusions: Higher levels of circulating neutrophil counts show a significant correlation with renal abnormalities and higher all-cause and CVD mortality in T2DM patients with DKD. The novel clinical predictive models and risk scores incorporating neutrophil counts may facilitate stratification and, hence, risk factor management in DKD patients.