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We aim to examine the relation of several folate forms (5-methyltetrahydrofolate (5-mTHF), unmetabolised folic acid (UMFA) and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18 757 participants from National Health and Nutrition Examination Survey 2011–2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 ml/min/1·73 m2), microalbuminuria (albumin:creatinine ratio (ACR) of 30–299 mg/g) and macroalbuminuria (ACR ≥ 300 mg/g). Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0·71; 95 % CI: 0·57, 0·87) and macroalbuminuria (OR, 0·65; 95 % CI: 0·46, 0·91) in participants in quartiles 3–4 (v. quartiles 1–2; both Pfor trend across quartiles <0·05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartiles 2–4 (v. quartile 1; OR, 2·12; 95 % CI: 1·45, 3·12; Pfor trend <0·001) and higher prevalence of macroalbuminuria in participants in quartile 4 (v. quartiles 1–3; OR, 1·46; 95 % CI: 1·06, 2·01; Pfor trend <0·001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all Pfor trend <0·01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, was associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.
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 8208 eligible participants without proteinuria at baseline were analysed from the renal substudy of the China Stroke Primary Prevention Trial. Participants were randomised to receive a double-blind daily treatment of 10 mg of enalapril and 0·8 mg of folic acid (n 4101) or 10 mg of enalapril only (n 4107). 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, 3088 (37·6 %) of the participants were male. The median treatment duration was 4·4 years. In the enalapril-only 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 quintiles 1–4. For those with enalapril and folic acid treatment, compared with the enalapril-only group, 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.
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