Abstract
BackgroundThe association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD.Methods and FindingsLongitudinal cohort study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria at baseline participating in medical health checkup program in a large worksite. Study participants were followed for incident CKD from 2002 through 2011. Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. CKD was defined as eGFR <60 mL/min per 1.73 m2. Parametric Cox models and pooled logistic regression models were used to estimate adjusted hazard ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8 person-years of follow-up. In age-adjusted models, the hazard ratios for CKD comparing quartiles 2–4 vs. quartile 1 of serum direct bilirubin were 0.93 (95% CI 0.67–1.28), 0.88 (0.60–1.27) and 0.60 (0.42–0.88), respectively. In multivariable models, the adjusted hazard ratio for CKD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41–0.87; P trend = 0.01). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of CKD.ConclusionsHigher serum direct bilirubin levels were significantly associated with a lower risk of developing CKD, even adjusting for a variety of cardiometabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for CKD risk.
Highlights
Chronic kidney disease (CKD) is an increasingly common public health problem [1,2]
Serum bilirubin plays a significant role in renal ischemiareperfusion injury [7,8] and, in patients with IgA nephropathy, mildly elevated serum bilirubin levels were negatively associated with the incidence of end-stage renal disease [9]
Serum total bilirubin levels were negatively associated with age and with a variety of metabolic parameters, including body mass index, glucose, total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, liver enzymes, C reactive protein (CRP), insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (Table 1)
Summary
Chronic kidney disease (CKD) is an increasingly common public health problem [1,2]. Persons with CKD have high rates of morbidity, mortality, health-care utilization, and progression to end-stage renal disease, with its corresponding complications [3,4]. Serum bilirubin plays a significant role in renal ischemiareperfusion injury [7,8] and, in patients with IgA nephropathy, mildly elevated serum bilirubin levels were negatively associated with the incidence of end-stage renal disease [9]. The association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD
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