Background Chronic kidney disease (CKD) and hepatitis C virus (HCV) infection are closely linked and both increase patient mortality. The association of HCV and risk of developing end-stage renal disease (ESRD) has not been analyzed with competing risk model. Method We enrolled a prospective cohort of 4,185 patients (mean age, 62 years; 41% female) registered in the CKD integrated care program at two affiliated hospitals of Kaohsiung Medical University in Taiwan between November 11, 2002 and May 31, 2009. With competing risk model, we analyzed the association of HCV infection, defined by seropositive of anti-HCV antibody, and hepatitis B virus (HBV) infection, defined by seropositive of HBV surface antigen, with the risk of entering ESRD. Results The prevalence of HCV infection was 7.6% and it increased with the CKD stages (trend test, P<0.001), while the prevalence of HBV infection was 7.4% and no specific trend among CKD stages (tend test, P = 0.1). During the 9,101 person-year follow-up period, there were 446 death and 1,205 patients entering ESRD. After adjusting death as the competing risk, the estimated 5-year cumulative incidence rate of ESRD among patients with and without HCV infection were 52.6% and 38.4%, respectively (modified log-rank, P<0.001). Multivariable analysis showed that HCV infection, but not HBV infection, had higher risk of developing ESRD compared with cases without infection (HCV, HR: 1.32, 95% CI: 1.07–1.62; HBV, HR: 1.10, 95% CI: 0.89–1.35). Subgroup analyses showed consistent results. Conclusions With death-adjusted competing risk analysis, HCV infection is associated with an increased risk of developing ESRD in CKD cohort.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization: N Engl J Med. 351: 1296–1305. doi: 10.1056/nejmoa041031
[3]
Wen CP, Cheng TY, Tsai MK, Chang YC, Chan HT, et al. (2008) All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462293 adults in Taiwan. Lancet 371: 2173–2182. doi: 10.1016/s0140-6736(08)60952-6
[4]
Foley RN, Murray AM, Li S, Herzog CA, McBean AM, et al. (2005) Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 16: 489–495. doi: 10.1681/asn.2004030203
[5]
Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH (2004) Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 164: 659–663. doi: 10.1001/archinte.164.6.659
[6]
Noordzij M, Leffondre K, Stralen KJV, Zoccali C, Dekker FW, et al. (2013) When do we need competing risks methods for survival analysis in nephrology? Nephrol Dial Transplant 28: 2670–2677. doi: 10.1093/ndt/gft355
[7]
Dalrymple LS, Katz R, Kestenbaum B, Shlipak MG, Sarnak MJ, et al. (2010) Chronic kidney disease and the risk of end-stage renal disease versus death. J Gen Intern Med 26: 379–385. doi: 10.1007/s11606-010-1511-x
[8]
De Nicola L, Chiodini P, Zoccali C, Borrelli S, Cianciaruso B, et al. (2011) SIN-TABLE CKD Study Group: Prognosis of CKD patients receiving outpatient nephrology care in Italy. Clin J Am Soc Nephrol 6: 2421–2428. doi: 10.2215/cjn.01180211
[9]
Meyers CM, Seeff LB, Stehman-Breen CO, Hoofnagle JH (2003) Hepatitis C and renal disease: an update. Am J Kidney Di 42: 631–657. doi: 10.1016/s0272-6386(03)00828-x
[10]
Perico N, Cattaneo D, Bikbov B, Remuzzi G (2009) Hepatitis C infection and chronic renal diseases. Clin J Am Soc Nephrol 4: 207–220. doi: 10.2215/cjn.03710708
[11]
Fabrizi F, Plaisier E, Saadoun D, Martin P, Messa P, et al. (2013) Hepatitis C virus infection, mixed cryoglobulinemia, and kidney disease. Am J Kidney Dis 61: 623–637. doi: 10.1053/j.ajkd.2012.08.040
[12]
Fabrizi F, Martin P, Dixit V, Messa P (2012) Hepatitis C virus infection and kidney disease: a meta-analysis. Clin J Am Soc Nephrol 7: 549–557. doi: 10.2215/cjn.06920711
[13]
Chen YC, Chiou WY, Hung SK, Su YC, Hwang SJ (2013) 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 Nephrology 14: 187. doi: 10.1186/1471-2369-14-187
[14]
Crook ED, Penumalee S, Gavini B, Filippova K (2005) Hepatitis C is a predictor of poorer renal survival in diabetic patients. Diabetes Care 28: 2187–2191. doi: 10.2337/diacare.28.9.2187
[15]
Tsui JI, Vittinghoff E, Shlipak MG, Bertenthal D, Inadomi J, et al. (2007) Association of hepatitis C seropositivity with increased risk for developing end-stage renal disease. Arch Intern Med 167: 1271–1276. doi: 10.1001/archinte.167.12.1271
[16]
Satapathy SK, Lingiseetty CS, Williams S (2012) Higher prevalence of chronic kidney disease and shorter renal survival in patients with chronic hepatitis C virus infection. Hepatol Int 6: 369–378. doi: 10.1007/s12072-011-9284-9
[17]
Su FH, Su CT, Chang SN, Chen PC, Sung FC, et al. (2012) Association of hepatitis C virus infection with risk of ESRD: a population-based study. Am J Kidey Dis 60: 553–560. doi: 10.1053/j.ajkd.2012.04.003
[18]
Liu WC, Hung CC, Chen SC, Yeh SM, Lin MY, et al. (2012) Association of hyperuricemia with renal outcomes, cardiovascular disease, and mortality. Clin J Am Soc Nephrol 7: 541–548. doi: 10.2215/cjn.09420911
[19]
Tsai YC, Tsai JC, Chen SC, Chiu YW, Hwang SJ, et al. (2014) Association of fluid overload with kidney disease progression in advanced CKD: a prospective cohort study. Am J Kidney Dis 63: 68–75. doi: 10.1053/j.ajkd.2013.06.011
[20]
Lee JJ, Lin MY, Yang YH, Lu SN, Chen HC, et al. (2010) Association of hepatitis C and B virus infection with CKD in an endemic area in Taiwan: a cross-sectional study. Am J Kidney Dis 56: 23–31. doi: 10.1053/j.ajkd.2010.01.015
[21]
Levey AS, Coresh J, Balk E, Kausz AT, Levin A, et al. (2003) National Kidney Foundation: National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139: 137–147. doi: 10.7326/0003-4819-139-2-200307150-00013
[22]
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, et al. (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130: 461–470. doi: 10.7326/0003-4819-130-6-199903160-00002
[23]
Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, et al. (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43: 1130–1139. doi: 10.1097/01.mlr.0000182534.19832.83
[24]
Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16: 1141–1154. doi: 10.1214/aos/1176350951
[25]
Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94: 496–509. doi: 10.1080/01621459.1999.10474144
[26]
Gray B. cmprsk: subdistribution analysis of competing risks. Available at: http://cran.r-project.org/web/packages/c？mprsk/index.html. Accessed December 30, 2013.
[27]
Chuang WL, Yu ML (2013) Host factors determining the efficacy of hepatitis C treatment. J Gastroenterol 48: 22–30. doi: 10.1007/s00535-012-0669-x
[28]
Conway B, Webster A, Ramsay G, Morgan N, Neary J, et al. (2009) Prediction mortality and uptake of renal replacement therapy in patients with stage 4 chronic kidney disease. Nephrol Dial transplant 24: 1930–1937. doi: 10.1093/ndt/gfn772
[29]
Barsoum RS (2007) Hepatitis C virus: from entry to renal injury-facts and potentials. Nephrol Dial Transplant 22: 1840–1848. doi: 10.1093/ndt/gfm205
[30]
W？rnle M, Schmid H, Banas B, Merkle M, Henger A, et al. (2006) Novel role of toll like receptor 3 in Hepatitis C-associated glomerulonephritis. Am J Pathol 168: 370–385. doi: 10.2353/ajpath.2006.050491
[31]
Zhu N, Khoshnan A, Schneider R, Matsumoto M, Dennert G, et al. (1998) Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor receptor 1 and enhances TNF-induced apoptosis. J Virol 72: 3691–3697.
[32]
Sheikh MY, Choi J, Qadri I, Friedman JE, Sanyal AJ (2008) Hepatitis C virus infection: molecular pathways to metabolic syndrome. Hepatology 47: 2127–2133. doi: 10.1002/hep.22269
[33]
Dai CY, Yeh ML, Huang CF, Hou CH, Hsieh MY, et al.. (2013) Chronic hepatitis C infection is associated with insulin resistance and lipid profile. J Gastroenterol Hepatol doi: 10.1111/jgh.12313.
[34]
Yu ML, Liu CH, Huang CF, Tseng TC, Huang JF, et al. (2012) Revisiting the stopping rule for hepatitis C genotype 1 patients treated with peginterferon plus ribavirin. PLoS ONE 7(12): e52048 doi:10.1371/journal.pone.0052048.
[35]
Hsu YC, Lin JT, Ho HJ, Kao YH, Huang YT, et al..(2013) Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology doi: 10.1002/hep.26892
[36]
Yang JF, Lin YY, Hsieh MH, Tsai CH, Liu SF, et al. (2011) Performance characteristics of a combined hepatitis C virus core antigen and anti-hepatitis C virus antibody test in different patient groups. Kaohsiung J Med Sci 27: 258–263. doi: 10.1016/j.kjms.2010.11.007
[37]
Yu ML, Dai CY, Huang CF, Lee JJ, Yeh ML, et al..(2013) High hepatitis B virus surface antigen levels and favorable interleukin 28B genotype predict spontaneous hepatitis C virus clearance in uremic patients. J Hepatol. doi: 10.1016/j.jhep.2013.09.023
[38]
Liu JY, Lin HH, Liu YC, Lee SS, Chen YL, et al. (2008) Extremely high prevalence and genetic diversity of hepatitis C virus infection among HIV-infected injection drug users in Taiwan. Clin Infect Dis 46: 1761–1768. doi: 10.1086/587992
