Hepatitis C Virus Viremia and Chronic Kidney Disease in HIV
Hepatitis C Virus Viremia and Chronic Kidney Disease in HIV
Background: Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined.
Methods: Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft–Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression.
Results: Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8–113.0) ml/min per 1.73 m. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5–14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype.
Conclusion: Compared with HIV-monoinfected patients, HIV-positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD.
Although the introduction of combination antiretroviral (ARV) treatment (cART) has resulted in a decrease in HIV-associated nephropathy, chronic kidney disease (CKD) remains an important cause of morbidity and mortality in HIV-positive patients. Apart from risk factors related to the HIV infection and its treatment, HIV-positive patients often have a higher prevalence of traditional risk factors for kidney disease, such as arterial hypertension, diabetes mellitus and smoking, than seen in the background population.
CKD has been reported to occur more often in HIV-positive patients coinfected with hepatitis C virus (HCV). HCV infection has been associated with different nephropathies, especially membranoproliferative glomerulonephritis in patients with mixed cryoglobulinemia. In the EuroSIDA study, we have previously shown that HCV-seropositive patients had a 75% increased risk of CKD compared with HCV-seronegative patients, and a recent meta-analysis showed that, compared to HIV-monoinfected patients, HIV/HCV-coinfected patients had a nearly 50% increased risk of CKD. However, in these and other published studies, the HCV diagnosis was based on a positive HCV antibody test only. The influence of HCV viral load and genotype on the risk of development of CKD in patients coinfected with HIV and HCV, therefore, remains to be determined.
In the developed world, chronic HCV infection is predominantly acquired through IDU. A number of renal disorders have been associated with use of illicit drugs (e.g. heroin and cocaine). In addition, IDU carries a high risk of invasive bacterial infections, which can lead to renal impairment. It is, therefore, likely that some of the increased renal morbidity and mortality seen in HCV-positive patients is due to some of these risk factors and not the HCV per se. Furthermore, in HCV patients with advanced liver disease, HCV could cause CKD indirectly as part of a hepatorenal syndrome.
In the EuroSIDA study, we are prospectively following a large cohort of HIV/HCV-coinfected patients, well characterized in terms of HCV-RNA and HCV genotype status. The aim of the present study was, therefore, to investigate the impact of HCV viremia and genotype on the risk of development of CKD in HIV/HCV-coinfected patients in the EuroSIDA study.
Abstract and Introduction
Abstract
Background: Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined.
Methods: Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft–Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression.
Results: Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8–113.0) ml/min per 1.73 m. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5–14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype.
Conclusion: Compared with HIV-monoinfected patients, HIV-positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD.
Introduction
Although the introduction of combination antiretroviral (ARV) treatment (cART) has resulted in a decrease in HIV-associated nephropathy, chronic kidney disease (CKD) remains an important cause of morbidity and mortality in HIV-positive patients. Apart from risk factors related to the HIV infection and its treatment, HIV-positive patients often have a higher prevalence of traditional risk factors for kidney disease, such as arterial hypertension, diabetes mellitus and smoking, than seen in the background population.
CKD has been reported to occur more often in HIV-positive patients coinfected with hepatitis C virus (HCV). HCV infection has been associated with different nephropathies, especially membranoproliferative glomerulonephritis in patients with mixed cryoglobulinemia. In the EuroSIDA study, we have previously shown that HCV-seropositive patients had a 75% increased risk of CKD compared with HCV-seronegative patients, and a recent meta-analysis showed that, compared to HIV-monoinfected patients, HIV/HCV-coinfected patients had a nearly 50% increased risk of CKD. However, in these and other published studies, the HCV diagnosis was based on a positive HCV antibody test only. The influence of HCV viral load and genotype on the risk of development of CKD in patients coinfected with HIV and HCV, therefore, remains to be determined.
In the developed world, chronic HCV infection is predominantly acquired through IDU. A number of renal disorders have been associated with use of illicit drugs (e.g. heroin and cocaine). In addition, IDU carries a high risk of invasive bacterial infections, which can lead to renal impairment. It is, therefore, likely that some of the increased renal morbidity and mortality seen in HCV-positive patients is due to some of these risk factors and not the HCV per se. Furthermore, in HCV patients with advanced liver disease, HCV could cause CKD indirectly as part of a hepatorenal syndrome.
In the EuroSIDA study, we are prospectively following a large cohort of HIV/HCV-coinfected patients, well characterized in terms of HCV-RNA and HCV genotype status. The aim of the present study was, therefore, to investigate the impact of HCV viremia and genotype on the risk of development of CKD in HIV/HCV-coinfected patients in the EuroSIDA study.
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