Cigarette smoking reduced renal function deterioration in hypertensive patients may be mediated by elevated homocysteine

Abstract

Elevated homocysteine (HCY) and smoking are both important risk factors for hypertensive patients. However, whether they have crossing effect on renal function deterioration of hypertensive patients and what is the underlying mechanism are unclear. In the present study, 3033 participants diagnosed as essential hypertension with estimated glomerular filtration rate (eGFR)> 30 ml/min/1.73 m2 from southern China were enrolled in this cross-sectional study. We collected the demographic and clinical data. In addition, the mediation effects were analyzed. The results showed that, comparing with non-smokers, smokers had significant higher levels of HCY (13.10 (11.20-16.87) vs. 11.00 (8.90-13.40) umol/L, P < 0.001) and lower eGFR (79.71 (66.83-91.05) vs. 82.89 (69.80-95.85) ml/min/1.73m2, P < 0.001). HCY levels and smoking were independently associated with decreased eGFR. Meanwhile, eGFR levels were significantly negatively correlated with HCY (P < 0.001), and this correlation might be stronger in current smokers. Current smoker consuming over 20 cigarettes per day would accelerate early renal function deterioration (OR = 1.859, P = 0.019). The mediation effects analysis further showed that the association between smoking and renal function deterioration was mediated by HCY. And elevated HCY was accounted for 56.94% of the estimated causal effect of smoking on renal function deterioration in hypertensive patients. Our findings indicated that cigarette smoking was associated with renal function deterioration in hypertensive patients, and the association between cigarette smoking and renal function deterioration was probably mediated by elevated HCY. Therefore, HCY-lowering therapy may be beneficial for renal function deterioration in hypertensive smoking patients.

Keywords: cigarette smoking; homocysteine; hypertension; renal function deterioration.

Figure 1

(A) Correlation between homocysteine (HCY) and estimated glomerular filtration rate (eGFR) in current smokers group, former smokers group, and never-smokers group respectively. (B) Correlation between HCY and eGFR in subjects with 60 ml/min/1.73 m² ≤ eGFR < 90 ml/min/1.73 m² classified by current smoking, former smoking, and never-smoking respectively.

Figure 2. Correlation between homocysteine (HCY) and estimated glomerular filtration rate (eGFR) in current smokers consuming over 20 cigarettes per day group, 11–20 cigarettes per day group, and no more than 10 cigarettes per day group

Figure 3

(A) The serum homocysteine (HCY) levels in current smokers group, former smokers group, and never-smokers group. *P < 0.05 vs. Never-Smokers; ▲P < 0.05 vs. Former Smokers. (B) The serum homocysteine (HCY) levels in current smokers consuming over 20 cigarettes per day group, 11–20 cigarettes per day group, and no more than 10 cigarettes per day group. (C) The serum homocysteine (HCY) levels in subjects with estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73m² group, 60 ml/min/1.73 m² ≤ eGFR < 90 ml/min/1.73 m² group, and 30 ml/min/1.73 m² ≤ eGFR < 60 ml/min/1.73 m² group. *P < 0.05 vs. eGFR ≥ 9 0 ml/min/1.73 m² group; ▲P < 0.05 vs. 60 ml/min/1.73 m² ≤ eGFR < 90 ml/min/1.73 m² group.

Figure 4. The estimated glomerular filtration rate (eGFR) levels in current smokers consuming over 20 cigarettes per day group, 11–20 cigarettes per day group, and no more than 10 cigarettes per day group

*P < 0.05 vs. no more than 10 cigarettes group; ▲P < 0.05 vs. 11–20 cigarettes per day group.

Figure 5. The mediation of homocysteine (HCY) on the association between smoking and deterioration of renal function in hypertensive patients (**P < 0.001, *P < 0.05)