Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients

We aimed to examine whether baseline neutrophil counts affected the risk of new-onset proteinuria in hypertensive patients, and, if so, whether folic acid treatment is particularly effective in proteinuria prevention in such a setting. A total of 8,208 eligible participants without proteinuria at baseline were analyzed from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT). Participants were randomized to receive a double-blind daily treatment of 10mg enalapril and 0.8mg folic acid (n=4,101) or 10mg enalapril alone (n=4,107). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean age of the participants was 59.5 (SD, 7.4) years, 3,088 (37.6%) of the participants were male. The median treatment duration was 4.4 years. In the enalapril-alone group, a significantly higher risk of new-onset proteinuria was found among participants with higher neutrophil counts (quintile 5; ≥4.8×109/L, OR, 1.44; 95%CI: 1.00, 2.06), compared with those in quintile 1-4. For those with enalapril and folic acid treatment, compared with the enalapril-alone, the new-onset proteinuria risk was reduced from 5.2% to 2.8% (OR, 0.49; 95%CI: 0.29, 0.82) among participants with higher neutrophil counts (≥4.8×109/L), whereas there was no significant effect among those with neutrophil counts <4.8×109/L. In summary, among hypertensive patients, those with higher neutrophil counts had increased risk of new-onset proteinuria, and this risk was reduced by 51% with folic acid treatment. If confirmed, neutrophil counts may serve as a biomarker to identify high-risk individuals who could particularly benefit from folic acid treatment.