Independent and combined effect of bilirubin and smoking on the progression of chronic kidney disease
Received 2 September 2017
Accepted for publication 23 November 2017
Published 15 January 2018 Volume 2018:10 Pages 121—132
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Professor Irene Petersen
Jiancheng Wang,1,* Binyan Wang,1,2,* Min Liang,1 Guobao Wang,1 Jianping Li,3 Yan Zhang,3 Yong Huo,3 Yimin Cui,4 Xiping Xu,1,5 Xianhui Qin1
1National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, 2Institute for Biomedicine, Anhui Medical University, Hefei, 3Department of Cardiology, 4Department of Pharmacy, Peking University First Hospital, Beijing, 5Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
*These authors contributed equally to this work
Objective: Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD) in hypertensive adults.
Methods: The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR of ≥50% if baseline eGFR was <60 mL/min/1.73 m2, or end-stage renal disease. The secondary outcomes included 1) rapid decline in renal function and 2) annual rate of eGFR decline.
Results: The median follow-up duration was 4.4 years. Cigarette smoking had no significant effect on the progression of CKD (odds ratio [OR]: 1.11, 95% confidence interval [95% CI]: 0.78–1.57). However, a significantly lower risk of the primary event (OR: 0.72, 95% CI: 0.55–0.95) was found in participants in tertile 3 compared to those in tertiles 1–2 for total bilirubin (TBiL) levels. More importantly, there was an interaction between TBiL and smoking status on the primary outcome (P for interaction =0.013). Among ever smokers, TBiL levels had no significant effect on the primary outcome. However, among never smokers, higher TBiL levels were significantly associated with a lower risk of the primary outcome (tertile 3 vs 1–2; OR: 0.53, 95% CI: 0.36–0.78). Similar trends were observed for direct bilirubin and secondary outcomes.
Conclusion: Among hypertensive patients, bilirubin was inversely associated with the progression of CKD in never smokers, but not in ever smokers.
Keywords: serum bilirubin, cigarette smoking, chronic kidney disease, hypertensive adults, rapid renal function decline, annual rate of eGFR decline
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