Association of serum total bilirubin levels with progressive renal decline and end-stage kidney disease: 10-year observational cohort study in Japanese patients with diabetes

Abstract

Objective Previous reports have demonstrated the association of serum bilirubin levels with the progression of diabetic nephropathy. The objective of this study is to assess the association of basal bilirubin levels with progressive renal decline (PRD) and end-stage kidney disease (ESKD). Methods A total of 298 patients with diabetes who visited Kyushu University Hospital (Japan) were recruited and followed up for 10 years. PRD was defined as a negative change in estimated glomerular filtration ratio (eGFR) >3.7%/year, 2.5th percentile. Logistic regression analysis was performed to evaluate the association of total bilirubin levels with PRD and its cut-off point was determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier method and Cox hazard regression analysis were used to evaluate the predictive ability of its cut-off point for ESKD. Results Logistic regression model showed that total bilirubin levels were significantly associated with PRD, and ROC analysis showed that its cut-off point was 0.5 mg/dL. Kaplan-Meier method showed that the percent of patients who reached two endpoints, composite endpoint (ESKD or doubling of creatinine level) or 30% eGFR decline, was significantly higher in the low bilirubin group than in the high bilirubin group (18.5% vs 11.0%, P = 0.045; 49.1% vs 42.1%, P = 0.045, respectively, log-rank test). Cox hazard regression models confirmed the independence of the predictive ability of its cut-off point. Conclusions Serum total bilirubin levels were negatively associated with PRD in diabetic nephropathy and its cut-off point was 0.5 mg/dL. It may be clinically useful for identifying patients at high risk of ESKD.

Temporal alteration of serum bilirubin levels and its renoprotective effects in diabetic kidney disease: exploring the hormonal mechanisms

“…( 14 ) showed that the serum total bilirubin level was significantly lower in DN patients compared with non-DN patients and was significantly associated with an increased risk of DN patients. A 10-year observational cohort study in Japanese patients with diabetes was to evaluate the association of baseline serum TBIL levels with progression of DN and found that serum TBIL levels were negatively associated with PRD in diabetic nephropathy and its cut-off point was 0.5 mg/dL ( 8 ). Liu M et al.…”

“…Eto et al. ( 8 ) further validated the clinical utility of serum TBIL (≤0.5 mg/dL) in predicting and identifying high risk of ESRD in DKD patients. These findings are rooted in the anti-inflammatory and anti-oxidative stress properties of bilirubin, which were examined in relation to serum bilirubin levels at a certain time point to delay DKD progression.…”

Association between serum total bilirubin and diabetic kidney disease in US diabetic patients

“…In the past twenty years, a series of cross-sectional studies have consistently suggested an association between high STB levels and a reduced risk of DKD in patients with diabetes (26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Concurrently, animal studies have been conducted to explore the mechanism whereby STB confers protection against DKD (36,37).…”

Association of Serum Bilirubin Levels with Macro- and Microvascular Complications in Chinese People with Type 2 Diabetes Mellitus: New Insight on Gender Differences

“…3,4 Bilirubin, as the final product of heme catabolism, includes total bilirubin (TBIL), indirect bilirubin (IBIL), and direct bilirubin (DBIL). 5 Recent studies have shown that bilirubin might be a possible candidate biomarker for DM 6 and diabetic complications [7][8][9] due to its potent antioxidant and anti-inflammatory properties. To date, there are few studies investigating the relationship between serum TBIL and diabetic vascular complications.…”