Peripheral neutrophil count and kidney outcomes in IgA nephropathy: a retrospective cohort study of 9,030 patients

Background Peripheral neutrophil (NEU) count is routinely measured in patients with immunoglobulin A (IgA) nephropathy (IgAN). However, its association with kidney outcomes remains unclear. Methods This retrospective, single-center study included 9,030 adults with biopsy-proven primary IgAN. Sequential Cox models compared NEU ≥4.0 versus < 4.0 × 10 9 /L using the rounded cohort median as the descriptive cutoff. Basic models were adjusted for age, sex, hypertension, and diabetes. Proteinuria and estimated glomerular filtration rate (eGFR) were then added separately and jointly. Sex, an antecedent factor, was examined as an illustrative comparison. Exploratory g -computation was used to estimate the proteinuria-related and remaining components of between-group differences in the 10-year outcome probabilities. Cross-sectional multinomial models examined report-derived crescent categories. Results Over a median follow-up of 9.3 years to kidney failure or censoring, 1,368 patients developed kidney failure, and 2,186 experienced a ≥50% decline in eGFR. For these outcomes, the basic-adjusted hazard ratios (HRs) comparing higher versus lower NEU were 1.22 (95%CI = 1.09–1.35) and 1.24 (95%CI = 1.14–1.35), respectively. These HRs attenuated to 1.00 (95%CI = 0.90–1.11) and 1.04 (95%CI = 0.95–1.13) after adjustment for proteinuria. The association with male sex also weakened or reversed after adjustment for kidney disease markers. The proteinuria-related components for NEU were 2.680 (95%CI = 2.221–3.125) and 3.623 (95%CI = 3.038–4.199) percentage points, with the remaining component intervals including zero for both outcomes. Sex also showed positive proteinuria-related components but retained a positive remaining component for ≥50% decline in eGFR. Among 8,968 patients with classifiable crescent lesions, higher NEU was associated with C1 and C2 categories versus C0, including after adjustment for proteinuria and eGFR. Conclusion A higher NEU count is associated with adverse kidney outcomes, with marked attenuation after adjustment for proteinuria. This attenuation is consistent with a substantial overlap between the NEU count and the markers of disease severity, particularly proteinuria. Whether proteinuria lies on a causal pathway cannot be determined from these data.