Abstract
Background
Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN).
Methods
We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
Results
Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04–1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend <0.01). When bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively.
Conclusions
We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.
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Acknowledgments
The authors would like to express our appreciation to the investigators at the participating institutions: Tetsuhiko Yoshida, M.D., Kei Hori, M.D., Ph.D., Takashi Inenaga, M.D., Akinori Nagashima, M.D., Ph.D., Tadashi Hirano, M.D. and Hideko Noguchi. This work was supported in part by Grants-in-Aid for Scientific Research (Nos. 23590400 and 24593302) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Conflict of interest
Honoraria: Kazuhiko Tsuruya (Kyowa Hakko Kirin Co., Chugai Pharmaceutical Co.), Research funding: Kazuhiko Tsuruya (Kyowa Hakko Kirin Co., Chugai Pharmaceutical Co., Fuso Pharmaceutical Industries, MSD K.K., Takeda Pharmaceutical Co.), Endowed department: Kazuhiko Tsuruya (Baxter). The authors declare that they have no relevant financial interests.
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Tanaka, S., Ninomiya, T., Masutani, K. et al. Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy. Clin Exp Nephrol 19, 1062–1070 (2015). https://doi.org/10.1007/s10157-015-1096-0
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DOI: https://doi.org/10.1007/s10157-015-1096-0