Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

Abstract

BACKGROUND:

Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary.

METHODS:

We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis.

RESULTS:

As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05).

CONCLUSIONS:

Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

• Authors: Sehoon Park, Do Hyoung Kim, Jin Ho Hwang, Yong-Chul Kim, Jin Hyuk Kim, Chun Soo Lim, Yon Su Kim, Seung Hee Yang, Jung Pyo Lee
• Journal: PloS one (PLoS One) Vol. 12 Issue 2 Pg. e0172434 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28225832 (Publication Type: Journal Article)

Chemical References

• Creatinine
• Bilirubin

Topics

• Aged
• Animals
• Apoptosis (drug effects)
• Bilirubin (blood, pharmacology)
• Creatinine (blood)
• Disease Models, Animal
• Disease Progression
• Female
• Fibrosis (blood, pathology, physiopathology)
• Glomerular Filtration Rate (physiology)
• Humans
• Kidney (drug effects, pathology, physiopathology)
• Kidney Diseases (blood, pathology, physiopathology)
• Kidney Function Tests
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Prognosis
• Prospective Studies
• Renal Insufficiency, Chronic (blood, pathology, physiopathology)
• Ureteral Obstruction (blood, pathology, physiopathology)