The predictive value of neutrophil-to-lymphocyte ratio for the occurrence, progression, and mortality of diabetic nephropathy: a systematic review and meta-analysis

The neutrophil-to-lymphocyte ratio (NLR) has emerged as a promising inflammatory biomarker in diabetic nephropathy (DN). However, its predictive value across the clinical spectrum of DN, from occurrence to progression and mortality, remains undefined. This study aimed to systematically evaluate the association between NLR and the risk, progression, and mortality of DN through a comprehensive meta-analysis. This systematic review and meta-analysis searched six databases for cohort and case-control studies published up to May 28, 2025. Pooled odds ratios (ORs) and standardized mean differences (SMDs) were calculated. Subgroup and sensitivity analyses explored heterogeneity. This review was prospectively registered in PROSPERO (CRD42024586927). Thirty-nine studies involving 14,300 participants showed that patients with diabetic nephropathy (DN) had higher NLR levels than diabetic controls without nephropathy, demonstrating a significant association between elevated NLR and DN occurrence (SMD = 1.31, 95% CI 0.96–1.66; OR = 2.16, 95% CI 1.85–2.52; both P < 0.00001). Among DN patients, those who experienced kidney function deterioration also exhibited higher NLR values than those with stable kidney function (SMD = 1.02, 95% CI 0.77–1.26, P < 0.00001; OR = 2.12, 95% CI 1.04–4.31, P = 0.04). The association with mortality was marginally non-significant (OR = 1.21, 95% CI 0.99–1.48, P = 0.06). Subgroup analyses showed stronger associations in patients aged ≥ 60 years and those with BMI ≥ 25 kg/m². NLR shows potential as a biomarker for identifying individuals at increased risk of DN occurrence and progression. Given the heterogeneity and possible publication bias among studies, these findings should be interpreted with caution and confirmed by future large-scale, standardized research.