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Hepatitis C Virus Infection Increases the Risk of Developing Chronic Kidney Disease: A Systematic Review and Meta-Analysis

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Abstract

Background and Rationale

Chronic kidney disease and hepatitis C virus are prevalent in the general population worldwide, and controversy exists about the impact of HCV infection on the development and progression of kidney disease.

Design

A systematic review of the published medical literature was made to assess whether positive anti-HCV serologic status plays an independent impact on the development of chronic kidney disease in the adult general population. We used a random-effects model to generate a summary estimate of the relative risk of chronic kidney disease (defined by reduced glomerular filtration rate or detectable proteinuria) with HCV across the published studies. Meta-regression and stratified analysis were also conducted.

Results

Twenty-three studies (n = 2,842,421 patients) were eligible, and separate meta-analyses were performed according to the outcome. Pooling results of longitudinal studies (n = 9; 1,947,034 unique patients) demonstrated a relationship between positive HCV serologic status and increased incidence of chronic kidney disease, the summary estimate for adjusted hazard ratio was 1.43 (95 % confidence interval 1.23; 1.63, P = 0.0001), and between-studies heterogeneity was noted (P value by Q test <0.0001). The risk of the incidence of chronic kidney disease associated with HCV, in the subset of Asian surveys, was 1.31 (95 % confidence interval 1.16; 1.45) without heterogeneity (P value by Q test = 0.6). HCV positive serology was an independent risk factor for proteinuria; adjusted odds ratio, 1.508 (95 % confidence intervals 1.19; 1.89, P = 0.0001) (n = 6 studies; 107,356 unique patients).

Conclusions

HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population.

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Abbreviations

ACEi:

Angiotensin-converting enzyme inhibitor

ARB:

Angiotensin receptor blocker

aHR:

Adjusted hazard ratio

aOR:

Adjusted odds ratio

aRR:

Adjusted relative risk

CKD:

Chronic kidney disease

CCI:

Charlson comorbidity index

CIs:

Confidence intervals

CV:

Cardiovascular

DM:

Diabetes mellitus

ESRD:

End-stage renal disease

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

ICD:

International classification of diseases

GFR:

Glomerular filtration rate

IFN:

Interferon

I 2 :

Ratio of true heterogeneity to total variation in observed effects

MC:

Mixed cryoglobulinemia

MDRD:

Modification of diet in renal disease

NA:

Not available

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement

References

  1. Eggers P. Has the incidence of end-stage renal disease in the USA and other countries stabilized ? Curr Opin Nephrol Hypertens. 2011;20:241–245.

    Article  PubMed  Google Scholar 

  2. Pol S, Vallet-Pichard A, Corouge M, Mallet V. Hepatitis C: epidemiology, natural history, and therapy. Contr Nephrol. 2012;76:1–9.

    Article  Google Scholar 

  3. Perico N, Cattaneo D, Bibkov B, Remuzzi G. Hepatitis C infection and chronic renal diseases. Clin J Am Soc Nephrol. 2009;4:207–220.

    Article  CAS  PubMed  Google Scholar 

  4. El-Serag H, Hampel H, Yeh C, Rabeneck L. Extrahepatic manifestations of hepatitis C among United States male veterans. Hepatology. 2002;36:1439–1445.

    Article  PubMed  Google Scholar 

  5. Kasuno K, Ono T, Matsumori A, et al. Hepatitis C virus-associated tubulo-interstitial injury. Am J Kidney Dis. 2003;41:767–775.

    Article  PubMed  Google Scholar 

  6. Sansonno D, Lauletta G, Montrone M, Grandaliano G, Schena F. Hepatitis C virus RNA and core protein in kidney glomerular and tubular structures isolated with laser capture microdissection. Clin Exp Immunol. 2005;140:498–506.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Gupta S, Eustace J, Winston J, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559–1585.

    Article  PubMed  Google Scholar 

  8. Kidney Disease: Improving Global Outcomes (KDIGO). Clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int. 2008;73:S1–S99.

  9. Liberati A, Altman D, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:e1–e34.

    Article  PubMed  Google Scholar 

  10. Poynard T, Conn H. The retrieval of randomised clinical trials in liver diseases from medical literature. A comparison of MEDLARS and manual methods. Control Clin Trials. 1985;6:271–279.

    Article  CAS  PubMed  Google Scholar 

  11. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute website. Available: http:/www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 16 Aug 2012.

  12. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266.

    Google Scholar 

  13. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.

    Article  CAS  PubMed  Google Scholar 

  14. Petitti D. Approaches to heterogeneity in meta-analysis. Stat Med. 2001;20:3625–3633.

    Article  CAS  PubMed  Google Scholar 

  15. Higgins J, Thompson S, Deeks J, Altman D. Measuring inconsistencies in meta-analysis. Br Med J. 2003;327:557–560.

    Article  Google Scholar 

  16. Chen Y, Chiou W, Su Y, Hwang S. Hepatitis C virus itself is a causal risk factor for chronic kidney disease beyond traditional risk factors: a 6-year nationwide cohort study across Taiwan. BMC Nephrol. 2013;14:187.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Lin M, Chiu Y, Lee C, et al. Factors associated with CKD in the elderly and nonelderly population. Clin J Am Soc Nephrol. 2013;8:33–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Tsui J, Vittinghoff E, Shlipak M, et al. Association of hepatitis C seropositivity with increased risk for developing end-stage renal disease. Arch Intern Med. 2007;167:1271–1276.

    Article  PubMed  Google Scholar 

  19. Moe S, Pampalone A, Ofner S, Rosenman M, Teal E, Hiu S. Association of hepatitis C virus infection with prevalence and development of kidney disease. Am J Kidney Dis. 2008;51:885–892.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Asrani S, Buchanan P, Pinski B, Rey L, Schnitzler M, Kanwal F. Lack of association between hepatitis C infection and chronic kidney disease. Clin Gastroenterol Hepatol. 2010;8:79–84.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Hofmann J, Torner A, Chow W, Ye W, Purdue M, Duberg A. Risk of kidney cancer and chronic kidney disease in relation to hepatitis C virus infection: a nationwide register-based cohort study in Sweden. Eur J Cancer Prev. 2011;20:326–330.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Butt A, Wang X, Fried L. HCV infection and the incidence of CKD. Am J Kidney Dis. 2011;57:396–402.

    Article  PubMed  Google Scholar 

  23. Su F, Su C, Chang S, et al. Association of hepatitis C virus infection with risk of ESRD: a population-based study. Am J Kidney Dis. 2012;60:553–560.

    Article  PubMed  Google Scholar 

  24. Chen Y, Lin H, Li C, Lee M, Su Y. A nationwide cohort study suggests that hepatitis C virus infection is associated with increased risk of chronic kidney disease. Kidney Int. 2014;85:1200–1207.

    Article  PubMed  Google Scholar 

  25. Lee J, Lin M, Chang J, et al. Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis. PLOS One. 2014;9:e100790.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Molnar M, Alhourani H, Wall B, et al. Association of hepatitis C viral infection with incidence and progression of chronic kidney disease in a large cohort of US veterans. Hepatology. 2015;61:1495–1502.

    Article  CAS  PubMed  Google Scholar 

  27. Tsui J, Vittinghoff E, Shlipak M, O’Hare A. Relationship between hepatitis C and chronic kidney disease: results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol. 2006;17:1168–1174.

    Article  PubMed  Google Scholar 

  28. Dalrymple L, Koepsell T, Sampson J, et al. Hepatitis C virus infection and the prevalence of renal insufficiency. Clin J Am Soc Nephrol. 2007;2:715–721.

    Article  CAS  PubMed  Google Scholar 

  29. Ishizaka N, Ishizaka Y, Seki G, Nagai R, Yamakado M, Koike K. Association between hepatitis B/C viral infection, chronic kidney disease and insulin resistance in individuals undergoing general health screening. Hepatol Res. 2008;38:775–783.

    Article  CAS  PubMed  Google Scholar 

  30. Lee J, Lin M, Yang Y, Lu S, Chen H, Hwang S. Association of hepatitis C and B virus infection with CKD in an endemic area in Taiwan. A cross-sectional study. Am J Kidney Dis. 2010;56:23–31.

    Article  PubMed  Google Scholar 

  31. Li W, Lee Y, Chen I, Wang S, Hsiao C, Loke S. Age and gender differences in the relationship between hepatitis C infection and all stages of chronic kidney disease. J Viral Hepat. 2014;21:706–715.

    Article  CAS  PubMed  Google Scholar 

  32. Liangpunsakul S, Chalasani N. Relationship between hepatitis C and microalbuminuria: results from the NHANES III. Kidney Int. 2005;67:285–290.

    Article  PubMed  Google Scholar 

  33. Huang J, Chuang W, Dai C, et al. Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link ? J Intern Med. 2006;260:255–262.

    Article  PubMed  Google Scholar 

  34. Yanik E, Lucas G, Vlahov D, Kirk G, Mehta S. HIV and proteinuria in an injection drug user population. Clin J Am Soc Nephrol. 2010;5:1836–1843.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Rhee M, Schmid C, Stevens L, Forrester J. Risk factors for proteinuria in HIV-infected and—uninfected Hispanic drug users. Am J Kidney Dis. 2008;52:683–690.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Fabrizi F, Martin P, Dixit V, Messa P. Hepatitis C virus infection and kidney disease: a meta-analysis. Clin J Am Soc Nephrol. 2012;7:549–557.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Park H, Adeyemi A, Henry L, Stepanova M, Younossi Z. A meta-analytic assessment of the risk of chronic kidney disease in patients with chronic hepatitis C virus infection. J Viral Hepat. 2015. doi:10.1111/jvh.12411.

    PubMed  Google Scholar 

  38. Wyatt C, Malvestutto C, Coca S, Klotman P, Parikh C. The impact of hepatitis C virus coinfection on HIV-related kidney disease: a systematic review and meta-analysis. AIDS. 2008;22:1799–1807.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Soma J, Saito T, Taguma Y, et al. High prevalence and adverse effects of hepatitis C virus infection in type II diabetic-related nephropathy. J Am Soc Nephrol. 2000;11:690–699.

    CAS  PubMed  Google Scholar 

  40. Crook E, Penumalee S, Gavini B, Filippova K. Hepatitis C is a predictor of poorer renal survival in diabetic patients. Diabetes Care. 2005;28:2187–2191.

    Article  PubMed  Google Scholar 

  41. Noureddine L, Usman S, Yu Z, Moorthi R, Moe S. Hepatitis C increases the risk of progression of chronic kidney disease in patients with glomerulonephritis. Am J Nephrol. 2010;32:311–316.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Arase Y, Suzuki F, Kawamura Y, et al. Development rate of chronic kidney disease in hepatitis C virus patients with advanced fibrosis after interferon therapy. Hepatol Res. 2011;41:946–954.

    Article  CAS  PubMed  Google Scholar 

  43. Bergman S, Accort N, Turner A, Glaze J. Hepatitis C infection is acquired pre-ESRD. Am J Kidney Dis. 2005;45:684–689.

    Article  PubMed  Google Scholar 

  44. Hsu Y, Lin J, Ho H, et al. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology. 2014;59:1293–1302.

    Article  CAS  PubMed  Google Scholar 

  45. Ble M, Aguilera V, Rubin A, et al. Improved renal function in liver transplant recipients treated for hepatitis C virus with a sustained virological response and mild chronic kidney disease. Liver Transpl. 2014;20:25–34.

    Article  PubMed  Google Scholar 

  46. Garg S, Hoenig M, Edwards E, et al. Incidence and predictors of acute kidney injury in an urban cohort of subjects with HIV and hepatitis C virus coinfection. AIDS Patient Care. 2011;25:135–141.

    Google Scholar 

  47. Mangia A, Ripoli M. Insulin resistance, steatosis, and hepatitis C virus. Hepatol Int. 2013;7:S782–S789.

    Article  Google Scholar 

  48. Kawaguchi T, Yoshida T, Harada M, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signalling 3. Am J Pathol. 2004;165:1499–1508.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus infection and diabetes. Direct involvement of the virus in the development of insulin resistance. Gastroenterology. 2004;126:840–848.

    Article  CAS  PubMed  Google Scholar 

  50. Fabrizi F, Dixit V, Messa P. Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality ? J Viral Hepat. 2012;1:601–609.

    Article  Google Scholar 

  51. Petta S, Macaluso F, Craxì A. Cardiovascular diseases and HCV infection: a simple association or more ? Gut. 2014;63:369–375.

    Article  PubMed  Google Scholar 

  52. Boddi M, Abbate R, Chellini B, et al. Hepatitis C virus RNA localization in human carotid plaques. J Clin Virol. 2010;47:72–75.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by a “Project Glomerulonephritis” Grant, in memory of Pippo Neglia, by Associazione Amici del Croff-Onlus. The funders had no role in study design, data collection analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Pad. Croff, via Commenda 15, 20122, Milan, Italy

    Fabrizio Fabrizi, Simona Verdesca & Piergiorgio Messa

  2. Division of Hepatology, University School of Medicine, Miami, FL, USA

    Fabrizio Fabrizi & Paul Martin

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  1. Fabrizio Fabrizi
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  2. Simona Verdesca
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Correspondence to Fabrizio Fabrizi.

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Fabrizi, F., Verdesca, S., Messa, P. et al. Hepatitis C Virus Infection Increases the Risk of Developing Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci 60, 3801–3813 (2015). https://doi.org/10.1007/s10620-015-3801-y

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  • DOI: https://doi.org/10.1007/s10620-015-3801-y

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