Association of Neutrophil Percentage‐to‐Albumin Ratio ( NPAR ) With Pathological Features and Long‐Term Prognosis in Diabetic Kidney Disease: A Cohort Study

ABSTRACT Growing evidence highlights the central role of inflammation in the onset and progression of DKD. In this study, we investigate the association between the neutrophil percentage‐to‐albumin ratio (NPAR) and clinicopathological features, as well as long‐term renal outcomes, in patients with diabetic kidney disease (DKD). Three hundred five biopsy‐confirmed DKD patients with baseline eGFR ≥ 15 mL/min/1.73 m 2 were retrospectively enrolled in this study. Baseline clinical and pathological characteristics were compared across NPAR quartiles. The primary outcome was 2‐year DKD progression, defined as a > 40% increase in serum creatinine, end‐stage renal disease, or all‐cause mortality. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses were conducted to examine the association between the NPAR and kidney outcomes. Subsequently, a prognostic nomogram was constructed for DKD patients incorporating NPAR to stratify individual risk. Higher baseline NPAR quartiles were significantly associated with renal dysfunction and advanced renal pathological lesions. In a subset of renal biopsy specimens, MPO immunostaining demonstrated increased renal neutrophil infiltration in patients with higher NPAR quartiles. Renal MPO expression was positively correlated with mesangial expansion, interstitial fibrosis, and tubular atrophy. Among patients with complete follow‐up, 65.3% developed the composite kidney outcome. Compared with the lowest NPAR quartile, multivariable‐adjusted odds ratios (95% CIs) for kidney outcomes were 1.68 (0.36–8.15), 6.21 (1.35–33.55), and 6.88 (1.27–46.86) for Q2, Q3, and Q4, respectively. RCS analysis indicated a nonlinear association between NPAR and kidney outcomes, with risk increasing sharply above an NPAR value of 1.38. Subgroup analyses identified significant interactions between NPAR and Kimmelstiel–Wilson nodules as well as SGLT2 inhibitor use on kidney outcomes. A prognostic model incorporating NPAR quartiles, age, total cholesterol, eGFR, and interstitial fibrosis demonstrated good discrimination (AUROC 0.863). In conclusion, elevated NPAR is associated with increased renal neutrophil infiltration, more severe histopathological injury, and adverse renal outcomes in patients with DKD, and independently predicts long‐term renal progression.