Skip to main content
SpringerLink
Log in

Elevated bilirubin levels and risk of developing chronic kidney disease: a dose–response meta-analysis and systematic review of cohort studies

  • Nephrology - Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Aims

Previous studies have indicated the link of bilirubin levels and risk of developing chronic kidney disease (CKD); however, the findings were inconsistent.

Methods

We searched for cohort studies examining bilirubin as an exposure and CKD as an outcome in the Medline, EMBASE, and Web of Science databases from inception through November 31, 2016. A generalized least-squares approach was applied to assess the dose–response relationship between them by pooling rate ratios with 95% confidence intervals. Subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted.

Results

Seven cohort studies with 1316 cases and 21,076 participants were identified for inclusion in the meta-analysis. The combined RR for the highest versus lowest bilirubin level was 0.36 (95% CI 0.19–0.68; P heterogeneity = 0.001; Power = 0.72; n = 6). In the linear dose–response analysis, each 1-μmol/L increase in bilirubin was associated with a 5% reduced risk of CKD (RR = 0.95; 95% CI 0.92–0.97; P for trend test = 0.113; P heterogeneity = 0.001; Power = 0.99; n = 7). The subgroup analyses and sensitivity analyses showed consistent results, and publication bias may exist.

Conclusion

This meta-analysis suggests that elevated bilirubin level may be associated with decreased risk of developing CKD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Said A, Desai C, Lerma EV (2015) Chronic kidney disease. Dis Mon DM 61(9):374–377. doi:10.1016/j.disamonth.2015.08.001

    Article  PubMed  Google Scholar 

  2. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, Kleefstra N, Naimark D, Roderick P, Tonelli M, Wetzels JF, Astor BC, Gansevoort RT, Levin A, Wen CP, Coresh J (2012) Age and association of kidney measures with mortality and end-stage renal disease. JAMA 308(22):2349–2360. doi:10.1001/jama.2012.16817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. GBD 2013 Mortality and Causes of Death Collaborators (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385(9963):117–171. doi:10.1016/S0140-6736(14)61682-2

    Article  Google Scholar 

  4. Xu XM, Cai GY, Bu R, Wang WJ, Bai XY, Sun XF, Chen XM (2015) Beneficial effects of caloric restriction on chronic kidney disease in rodent models: a meta-analysis and systematic review. PLoS ONE 10(12):e0144442. doi:10.1371/journal.pone.0144442

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet (London, England) 382(9888):260–272. doi:10.1016/s0140-6736(13)60687-x

    Article  Google Scholar 

  6. Fung E, Kurella Tamura M (2016) Epidemiology and public health concerns of CKD in older adults. Adv Chronic Kidney Dis 23(1):8–11. doi:10.1053/j.ackd.2015.10.001

    Article  PubMed  PubMed Central  Google Scholar 

  7. Turchetti G, Bellelli S, Amato M, Bianchi S, Conti P, Cupisti A, Panichi V, Rosati A, Pizzarelli F (2016) The social cost of chronic kidney disease in Italy. Eur J Health Econ HEPAC Health Econ Prev Care. doi:10.1007/s10198-016-0830-1

    Google Scholar 

  8. McQueen RB, Farahbakhshian S, Bell KF, Nair KV, Saseen JJ (2017) Economic burden of comorbid chronic kidney disease and diabetes. J Med Econ. doi:10.1080/13696998.2017.1288127

    PubMed  Google Scholar 

  9. Huang FY, Peng Y, Huang BT, Yang Y, Pu XB, Chen SJ, Gui YY, Xia TL, Chen F, Liu RS, Zhu Y, Chen M (2016) The correlation between serum total bilirubin and outcomes in patients with different subtypes of coronary artery disease. Clin Chim Acta Int J Clin Chem 465:101–105. doi:10.1016/j.cca.2016.12.020

    Article  Google Scholar 

  10. Boon AC, Bulmer AC, Coombes JS, Fassett RG (2014) Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations. Am J Physiol Ren Physiol 307(2):F123–F136

    Article  CAS  Google Scholar 

  11. Huang SS, Huang PH, Wu TC, Chen JW, Lin SJ (2012) Association of serum bilirubin with contrast-induced nephropathy and future cardiovascular events in patients undergoing coronary intervention. PLoS ONE 7(8):e42594. doi:10.1371/journal.pone.0042594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li JM, Shah AM (2003) ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. J Am Soc Nephrol JASN 14(8 Suppl 3):S221–S226

    Article  CAS  PubMed  Google Scholar 

  13. Sharma K, Cook A, Smith M, Valancius C, Inscho EW (2005) TGF-beta impairs renal autoregulation via generation of ROS. Am J Physiol Ren Physiol 288(5):F1069–F1077. doi:10.1152/ajprenal.00345.2004

    Article  CAS  Google Scholar 

  14. Thannickal VJ, Fanburg BL (1995) Activation of an H2O2-generating NADH oxidase in human lung fibroblasts by transforming growth factor beta 1. J Biol Chem 270(51):30334–30338

    Article  CAS  PubMed  Google Scholar 

  15. Idelman G, Smith DL, Zucker SD (2015) Bilirubin inhibits the up-regulation of inducible nitric oxide synthase by scavenging reactive oxygen species generated by the toll-like receptor 4-dependent activation of NADPH oxidase. Redox Biol 5:398–408. doi:10.1016/j.redox.2015.06.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P(2013) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. 2015

  17. Drewes HW, Steuten LM, Lemmens LC, Baan CA, Boshuizen HC, Elissen AM, Lemmens KM, Meeuwissen JA, Vrijhoef HJ (2012) The effectiveness of chronic care management for heart failure: meta-regression analyses to explain the heterogeneity in outcomes. Health Serv Res 47(5):1926–1959. doi:10.1111/j.1475-6773.2012.01396.x

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang J, Li Y, Han X, Hu H, Wang F, Yu C, Li X, Yang K, Yuan J, Yao P, Miao X, Wei S, Wang Y, Chen W, Liang Y, Zhang X, Guo H, Pan A, Yang H, Wu T, He M (2016) Association between serum bilirubin levels and decline in estimated glomerular filtration rate among patients with type 2 diabetes. J Diabetes Complicat 30(7):1255–1260

    Article  PubMed  Google Scholar 

  19. Tanaka S, Ninomiya T, Masutani K, Nagata M, Tsuchimoto A, Tsuruya K, Kitazono T (2015) Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy. Clin Exp Nephrol 19(6):1062–1070. doi:10.1007/s10157-015-1096-0

    Article  CAS  PubMed  Google Scholar 

  20. Sakoh T, Nakayama M, Tanaka S, Yoshitomi R, Ura Y, Nishimoto H, Fukui A, Shikuwa Y, Tsuruya K, Kitazono T (2015) Association of serum total bilirubin with renal outcome in Japanese patients with stages 3–5 chronic kidney disease. Metab, Clin Exp 64(9):1096–1102. doi:10.1016/j.metabol.2015.06.006

    Article  CAS  Google Scholar 

  21. Chin HJ, Cho HJ, Lee TW, Na KY, Oh KH, Joo KW, Yoon HJ, Kim YS, Ahn C, Han JS, Kim S, Jeon ES, Jin DC, Kim YL, Park SH, Kim CD, Song YR, Kim SG, Kim YG, Lee JE, Oh YK, Lim CS, Lee SK, Chae DW, Cho WY, Kim HK, Jo SK (2009) The mildly elevated serum bilirubin level is negatively associated with the incidence of end stage renal disease in patients with IgA nephropathy. J Korean Med Sci 24(Suppl):S22–S29. doi:10.3346/jkms.2009.24.S1.S22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shin HS, Jung YS, Rim H (2011) Relationship of serum bilirubin concentration to kidney function and 24-hour urine protein in Korean adults. BMC Nephrol 12:29. doi:10.1186/1471-2369-12-29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Thompson SG, Sharp SJ (1999) Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med 18(20):2693–2708

    Article  CAS  PubMed  Google Scholar 

  24. Nishimura T, Tanaka M, Sekioka R, Itoh H (2015) Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitus. J Diabetes Complicat 29(8):1223–1227. doi:10.1016/j.jdiacomp.2015.07.007

    Article  PubMed  Google Scholar 

  25. Targher G, Bosworth C, Kendrick J, Smits G, Lippi G, Chonchol M (2009) Relationship of serum bilirubin concentrations to kidney function and albuminuria in the United States adult population. Findings from the National Health and Nutrition Examination Survey 2001–2006. Clin Chem Lab Med 47(9):1055–1062. doi:10.1515/cclm.2009.244

    Article  CAS  PubMed  Google Scholar 

  26. Oda E, Aoyagi R, Aizawa Y (2012) Hypobilirubinemia might be a possible risk factor of end-stage kidney disease independently of estimated glomerular filtration rate. Kidney Blood Press Res 36(1):47–54. doi:10.1159/000339027

    Article  PubMed  Google Scholar 

  27. Tanaka M, Fukui M, Okada H, Senmaru T, Asano M, Akabame S, Yamazaki M, Tomiyasu K, Oda Y, Hasegawa G, Toda H, Nakamura N (2014) Low serum bilirubin concentration is a predictor of chronic kidney disease. Atherosclerosis 234(2):421–425. doi:10.1016/j.atherosclerosis.2014.03.015

    Article  CAS  PubMed  Google Scholar 

  28. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283(15):2008–2012

    Article  CAS  PubMed  Google Scholar 

  29. Ryu S, Chang Y, Zhang Y, Woo HY, Kwon MJ, Park H, Lee KB, Son HJ, Cho J, Guallar E (2014) Higher serum direct bilirubin levels were associated with a lower risk of incident chronic kidney disease in middle aged Korean men. PLoS ONE 9(2):e75178. doi:10.1371/journal.pone.0075178

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hamling J, Lee P, Weitkunat R, Ambuhl M (2008) Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med 27(7):954–970. doi:10.1002/sim.3013

    Article  PubMed  Google Scholar 

  31. Liu TZ, Xu C, Rota M, Cai H, Zhang C, Shi MJ, Yuan RX, Weng H, Meng XY, Kwong JS, Sun X (2017) Sleep duration and risk of all-cause mortality: a flexible, non-linear, meta-regression of 40 prospective cohort studies. Sleep Med Rev 32:28–36. doi:10.1016/j.smrv.2016.02.005

    Article  PubMed  Google Scholar 

  32. Sterne JA, Gavaghan D, Egger M (2000) Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 53(11):1119–1129

    Article  CAS  PubMed  Google Scholar 

  33. Aune D, Chan DS, Lau R, Vieira R, Greenwood DC, Kampman E, Norat T (2011) Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. BMJ (Clin Res ed) 343:d6617. doi:10.1136/bmj.d6617

    Article  Google Scholar 

  34. Aune D, Norat T, Vatten LJ (2014) Body mass index and the risk of gout: a systematic review and dose-response meta-analysis of prospective studies. Eur J Nutr 53(8):1591–1601. doi:10.1007/s00394-014-0766-0

    Article  PubMed  Google Scholar 

  35. Guo P, Huang G, Ren L, Chen Y, Zhou Q (2016) Number of parity and the risk of non-Hodgkin lymphomas: a dose-response meta-analysis of observational studies. Hematology. doi:10.1080/10245332.2016.1252002

    Google Scholar 

  36. Orsini N, Bellocco R, Greenland S (2005) Generalized least squares for trend estimation of summarized dose-response data. Stata J 6(1):40–57

    Google Scholar 

  37. Orsini N (2013) Multivariate dose-response meta-analysis: An update on glst. Available at: http://www.stata.com/meeting/nordic-and-baltic13/abstracts. Accessed May 2015

  38. Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D (2012) Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 175(1):66–73. doi:10.1093/aje/kwr265

    Article  PubMed  Google Scholar 

  39. Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309

    Article  CAS  PubMed  Google Scholar 

  40. Crippa A, Orsini N (2016) Dose-response meta-analysis of differences in means. BMC Med Res Methodol 16:91. doi:10.1186/s12874-016-0189-0

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kazancioglu R (2013) Risk factors for chronic kidney disease: an update. Kidney Int Suppl 3(4):368–371. doi:10.1038/kisup.2013.79

    Article  Google Scholar 

  42. Sun X, Ioannidis JP, Agoritsas T, Alba AC, Guyatt G (2014) How to use a subgroup analysis: users’ guide to the medical literature. JAMA 311(4):405–411. doi:10.1001/jama.2013.285063

    Article  CAS  PubMed  Google Scholar 

  43. Higgins J, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. Available from http://www.cochrane-handbook.org

  44. Doi SA, Barendregt JJ, Khan S, Thalib L, Williams GM (2015) Advances in the meta-analysis of heterogeneous clinical trials II: the quality effects model. Contemp Clin Trials 45(Pt A):123–129. doi:10.1016/j.cct.2015.05.010

    Article  PubMed  Google Scholar 

  45. Doi SA, Barendregt JJ, Khan S, Thalib L, Williams GM (2015) Simulation comparison of the quality effects and random effects methods of meta-analysis. Epidemiology 26(4):e42–e44. doi:10.1097/ede.0000000000000289

    Article  PubMed  Google Scholar 

  46. Doi SA, Thalib L (2008) A quality-effects model for meta-analysis. Epidemiology 19(1):94–100. doi:10.1097/EDE.0b013e31815c24e7

    Article  PubMed  Google Scholar 

  47. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hedges LV, Pigott TD (2001) The power of statistical tests in meta-analysis. Psychol Methods 6(3):203–217

    Article  CAS  PubMed  Google Scholar 

  49. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  50. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  51. Sim J, Wright CC (2005) The kappa statistic in reliability studies: use, interpretation, and sample size requirements. Phys Therapy 85(3):257–268

    Google Scholar 

  52. Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174

    Article  CAS  PubMed  Google Scholar 

  53. Huang SS, Huang PH, Wu TC, Chen JW, Lin SJ (2012) Association of serum bilirubin with contrast-induced nephropathy and future cardiovascular events in patients undergoing coronary intervention. PLoS ONE 7(8):e42594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee AT, Wang YY, Lin SY, Liang JT, Sheu WH, Song YM, Chang WD (2015) Higher serum total bilirubin concentration is associated with lower risk of renal insufficiency in an adult population. Int J Clin Exp Med 8(10):19212–19222

    PubMed  PubMed Central  Google Scholar 

  55. Jo J, Yun JE, Lee H, Kimm H, Jee SH (2011) Total, direct, and indirect serum bilirubin concentrations and metabolic syndrome among the Korean population. Endocrine 39(2):182–189. doi:10.1007/s12020-010-9417-2

    Article  CAS  PubMed  Google Scholar 

  56. Nakagami T, Toyomura K, Kinoshita T, Morisawa S (1993) A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochem Biophys Acta 1158(2):189–193

    Article  CAS  PubMed  Google Scholar 

  57. Song S, Wang S, Ma J, Yao L, Xing H, Zhang L, Liao L, Zhu D (2013) Biliverdin reductase/bilirubin mediates the anti-apoptotic effect of hypoxia in pulmonary arterial smooth muscle cells through ERK1/2 pathway. Exp Cell Res 319(13):1973–1987. doi:10.1016/j.yexcr.2013.05.015

    Article  CAS  PubMed  Google Scholar 

  58. Sano K, Nakamura H, Matsuo T (1985) Mode of inhibitory action of bilirubin on protein kinase C. Pediatr Res 19(6):587–590

    Article  CAS  PubMed  Google Scholar 

  59. Fevery J (2008) Bilirubin in clinical practice: a review. Liver Int Off J Int Assoc Study Liver 28(5):592–605. doi:10.1111/j.1478-3231.2008.01716.x

    Article  CAS  Google Scholar 

  60. Riphagen IJ, Deetman PE, Bakker SJ, Navis G, Cooper ME, Lewis JB, de Zeeuw D, Lambers Heerspink HJ (2014) Bilirubin and progression of nephropathy in type 2 diabetes: a post hoc analysis of RENAAL with independent replication in IDNT. Diabetes 63(8):2845–2853. doi:10.2337/db13-1652

    Article  CAS  PubMed  Google Scholar 

  61. Lee MJ, Kwon S, Kim JH, Seo JY, Park SB, Nam YJ, Ahn KH, Jeon YK, Kim BH, Moon S, Chun SW, Kim IJ, Kim SS (2015) High serum bilirubin concentration predicts the progression of chronic kidney disease in patients with type 2 diabetes mellitus and preserved kidney function. Diabetes 64:A155–A156

    Google Scholar 

  62. Han SS, Na KY, Chae DW, Kim YS, Kim S, Chin HJ (2010) High serum bilirubin is associated with the reduced risk of diabetes mellitus and diabetic nephropathy. Tohoku J Exp Med 221(2):133–140

    Article  CAS  PubMed  Google Scholar 

  63. Katoh T, Kawamoto R, Kohara K, Miki T (2015) Association between serum bilirubin and estimated glomerular filtration rate among diabetic patients. Int Sch Res Notices 2015:480418. doi:10.1155/2015/480418

    PubMed  PubMed Central  Google Scholar 

  64. Kawamoto R, Ninomiya D, Hasegawa Y, Kasai Y, Kusunoki T, Ohtsuka N, Kumagi T (2014) Association between serum bilirubin and estimated glomerular filtration rate among elderly persons. PLoS ONE 9(12):e115294. doi:10.1371/journal.pone.0115294

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kuriyama S, Maruyama Y, Nishio S, Takahashi Y, Kidoguchi S, Kobayashi C, Takahashi D, Sugano N, Hosoya T, Yokoo T (2015) Serum uric acid and the incidence of CKD and hypertension. Clin Exp Nephrol 19(6):1127–1134. doi:10.1007/s10157-015-1120-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Liao WC, Tu YK, Wu MS, Lin JT, Wang HP, Chien KL (2015) Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis. BMJ (Clin Res ed) 349:g7371. doi:10.1136/bmj.g7371

    Google Scholar 

  67. Wang X, Ouyang Y, Liu J, Zhu M, Zhao G, Bao W, Hu FB (2014) Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ (Clin Res ed) 349:g4490. doi:10.1136/bmj.g4490

    Google Scholar 

  68. Yang WS, Va P, Wong MY, Zhang HL, Xiang YB (2011) Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies. Am J Clin Nutr 94(6):1575–1583. doi:10.3945/ajcn.111.020966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr. Chang Xu, a Ph.D. student at the Chinese Evidence-Based Medicine Center and the Chinese Cochrane Center, for helpful comments and suggestions on this manuscript.

Author information

Author notes

  1. Jun Wang, Peng Guo and ZhengYan Gao have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China

    Jun Wang

  2. Department of Hepatobiliary and Pancreatic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China

    Peng Guo

  3. Department of Urology, The Sixth People’s Hospital of Yancheng City, Yancheng, 224000, China

    ZhengYan Gao

  4. Department of Gastroenterology, Huangshi Central Hospital of E Dong Healthcare Group, Affiliated Hospital of Hubei Polytechnic University, Huangshi, 435000, China

    BenGang Zhou

  5. Department of Joint Surgery, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China

    Lei Ren

  6. Department of Spinal Surgery, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China

    Yu Chen

  7. Department of Science and Education, The First People’s Hospital of Changde City, No. 318 Renming Road, Changde, 415003, Hunan, China

    Quan Zhou

Authors
  1. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ZhengYan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. BenGang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Quan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Quan Zhou.

Ethics declarations

Conflict of interest

The authors have declared that no conflict of interest exists.

Human and animal rights

Compliance with ethical standards and this article does not contain any studies with human participants performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the primary study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 702 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Guo, P., Gao, Z. et al. Elevated bilirubin levels and risk of developing chronic kidney disease: a dose–response meta-analysis and systematic review of cohort studies. Int Urol Nephrol 50, 275–287 (2018). https://doi.org/10.1007/s11255-017-1675-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-017-1675-y

Keywords

Search

Navigation