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Higher prevalence of chronic kidney disease
and shorter renal survival in patients with chronic hepatitis C virus infection
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from Jules: this study conducted in East Harlem, NY found HCV & kidney associated but a number of other potentially causative factors were present including IVDU, patients predisposed to kidney disease - African-Americans, Latinos - having other comorbid conditions that is metabolic syndrome, hypertension, diabetes. Nonetheless, these are common characteristics of those with HCV in inner city areas & underscore that kidney disease is an important concern for people with HC. Of note this studies fimdings suggest a higher HCV viral load may be causative or contribute to kidney disease in HCV+.
Higher prevalence of chronic kidney disease and shorter renal survival in patients with chronic hepatitis C virus infection.......this study was conducted in NYC at Metroplitan Hospital which is in East Harlem.....Majority of the included patients were of Hispanic and African-American origin. However, a significant number of the patients in the HCV group had history of IVDU [128 (23.2%) vs. 6 (1.9%), P<0.0005] and positive HIV status [42 (7.6%) vs. 4 (1.3%), P<0.0005].......[Although the current study also emphasized that
history of IFN treatment may have a protective effect, this fact needs to be further verified in larger prospectively designed study].......Despite its limitations this study provides a number of relevant and novel observations. We focused on determining the prevalence of CKD in a large cohort of chronic HCV-infected ambulatory patients and highlighted the significantly increased prevalence. The study further confirmed that the progression to CKD and ESRD is more rapid in HCV-infected patients, and the progression to CKD is independent of the effect of the presence or absence of DM. In addition to conventional metabolic risk factors such as DM and presence of hypertension, a baseline viral load[7 9 105 emerged as an important predictor of CKD.......we found a significantly higher prevalence of CKD in patients with chronic HCV infection compared to the control population by serial estimation of GFR and proteinuria (9.6 vs. 5.1%, P = 0.02). Further, the prevalence of CKD remained significant in HCV-infected patients regardless of whether CKD was defined in terms of creatinine measurements, proteinuria, GFR, or a combination of the parameters. Thus, the study further strengthens the potential positive association of HCV infection and development of CKD as reported previously [4-6]. With increasing age, more patients in the HCV group had CKD compared with the control group, although the differences did not reach statistical significance. The disparity of developing CKD between patients who have HCV infection and those who do not reach almost fivefold in patients aged >70 years. An age dependent association also has been reported for HCV and diabetes [14, 15]. It is plausible that non hepatic manifestations of HCV, such as development of CKD and diabetes, develop after many years of chronic infection. Case series of patients with membranoproliferative glomerulonephritis (MPGN) and HCV describe the average age to be >/=50 years [16, 17]. In the HCV group, components of metabolic syndrome such as hypertension and DM emerged as independent positive predictors for development of CKD......Earlier studies have reported a rapid progression of diabetic nephropathy in patients infected with HCV [9]. We found significantly shorter time to develop CKD in HCV-infected patients compared to controls without HCV infection irrespective of the presence or absence of DM. Although the mechanism of HCV-related renal disease is uncertain, research suggests that glomerular injury results from deposition of circulating immune complexes that contain hepatitis C antibody, antigens, and complement [18]. It also could be a result of accelerated atherosclerosis among individuals with HCV, which has been suggested in some studies [19-21]. Thus, although the current study further supports a casual role of HCV in the pathogenesis of CKD, the mechanism for progression to CKD may not necessarily be related to HCV alone; a potential role of metabolic syndrome related to chronic HCV infection leading to accelerated atherosclerosis may also be implicated.
we hypothesize a direct role of ''high viral
load'' in causing glomerular injury in patients with chronic
HCV infection and in the development of CKD
Higher viral load has been reported in patients with chronic HCV infections and ESRD compared to controls [24]. Although in the current study, the mean viral loads in the HCV group with and without CKD were not significantly different on their first evaluations, baseline viral load [7 < 105 cps/mL significantly predicted the development of CKD. Similar relationship was observed in a recent smaller study that involved 19 HCV-positive patients who had a persistently elevated viral load ([1 million cps/mL) during follow-up for[1.5 years, and 17 HCV patients who had a persistently low viral load (<10,000 cps/mL) during follow-up [25]. At the beginning of follow-up, patients in the two groups had similar kidney function. During 2.6 years of follow-up none of the patients received treatment for HCV, mean GFR decreased significantly with a persistently elevated viral load (P = 0.003). Based on these findings, we hypothesize a direct role of ''high viral load'' in causing glomerular injury in patients with chronic HCV infection and in the development of CKD. Although the current study is not designed to prove or disprove such a fact, it definitely opens the gate for more research on this intriguing finding.
Proteinuria was noted in a significantly higher number of patients with chronic HCV infection [6.8 vs. 2.9%, P = 0.024]. A significant proportion of the HCV-infected patients with proteinuria had non-nephrotic range of proteinuria (4.7 vs. 1.8%, P = 0.04). Nephrotic-range proteinuria was noted in 9 (2.1%) patients who developed CKD in the HCV group compared to 3 (1.1%) in the control group (P = 0.39). In the current study, it is not entirely clear whether HCV is primarily responsible for the range of observed proteinuria, or whether associated comorbid conditions such as DM, hypertension, and HIV (which are known risk factors for the development of CKD) also played an etiologic role (Table 4). Besides, in a logistic regression analysis DM and hypertension were significantly associated with CKD in hepatitis C infected patients. However, except for HIV infection and history of IVDU, these comorbid conditions are not significantly different in the HCV group and the controls, thus does not entirely negate a direct pathogenetic role of HCV infection.
Hepatol Int (2012)
Sanjaya Kumar Satapathy
Chandra Sekhar Lingisetty
Susan Williams
On multivariate regression analysis, only higher age (P = 0.004; OR 1.06; 95% CI 1.01-1.10), hypertension (P = 0.02; OR 2.68; 95% CI 1.15-6.22), HCV
PCR[7 x 105 cps/mL (P = 0.01, OR 2.45; 95% CI 1.21-4.98), and DM (P = 0.02, OR 2.37; CI 1.14-4.91) were noted as significant independent positive predictors for CKD.......The mean estimated time to develop CKD was significantly shorter in the HCV group compared to the control group (74 vs. 84 months, P\0.001; log rank) by Kaplan-Meyer survival analysis (Fig. 4a).
The study was conducted at the Metropolitan Hospital Center.
All consecutive patients with serum positive for antibody to hepatitis C, seen at the outpatient gastroenterology as well as medicine clinic between January 2003 and October 2006 were enrolled into this study. Controls were selected from a list of 1,847 consecutive patients after filtering out HCV-infected patients (hepatitis C diagnosis based on the ICD code) seen at the outpatient gastroenterology clinic over a period of 1 year from October 2005 to October 2006.
Majority of the included patients were of Hispanic and African-American origin. However, a significant number of the patients in the HCV group had history of IVDU [128 (23.2%) vs. 6 (1.9%), P<0.0005] and positive HIV status [42 (7.6%) vs. 4 (1.3%), P<0.0005].......this study evaluated predominantly African-American and Hispanic patients in the USA, a cohort with a high prevalence of HIV, suggesting IVDU or multiple sexual partners as the major cause for the high prevalence of hepatitis C. Thus, results may not be generalizable to other races and geographic areas.
Abstract
Background The role of hepatitis C virus infection (HCV) in the etiology and progression of chronic kidney disease (CKD) is controversial.
Aim To measure the prevalence of CKD and evaluate its course in patients with chronic HCV infection.
Methods A retrospective analysis was done after excluding patients with nephrolithiasis, structural kidney disease, and those with missing clinical information on 552 anti-HCV-positive patients and 313 patients without known HCV infection matched for age, race, and gender. CKD was defined as estimated glomerular filtration rate value of\60 mL/min/1.73 m2 and/or persistence of proteinuria ([3 months) on urine analysis by dipstick. Viral load obtained during the initial evaluation was defined as ''baseline viral load''.
Results
The prevalence of CKD in the anti-HCV-positive group was significantly higher compared to control group [53 (9.6%) vs. 16 (5.1%), P = 0.02].
On multivariate regression analysis, higher age, hypertension, HCV PCR [7 x 105 cps/mL, and diabetes mellitus were significant independent positive predictors, whereas history of interferon treatment was significant independent negative predictor for CKD.
Male gender, human immunodeficiency virus status, body weight, intravenous drug use, and HCV genotype were not predictors of CKD. Analysis of renal
survival through Kaplan-Meyer curves revealed significantly shorter time to develop CKD (74 vs. 84 months, P<0.001; log rank) and end-stage renal disease (79.9 vs. 86.5 months, P = 0.005; log rank) in the HCV group compared to the control group.
Conclusion
Chronic HCV infection was associated with a significantly higher prevalence of CKD compared with controls, as well as significantly shorter renal survival.
A higher baseline viral load is an independent predictor of CKD.
HCV+ Tended to Have Higher HCV Viral Load
Data on HCV viral load at baseline were available in 451 (81.7%) of the patients. The mean viral load was not significantly different at baseline in the group that developed CKD compared to those who never developed CKD [(4.64 ± 3.32) vs. (4.58 ± 5.56) 9 105 cps/mL; P = 0.24]. However, when we performed a sensitivity analysis using a series of cut-offs for viral loads ranging from 4 x 105 cps/mL through 8 9 105 cps/mL, the frequency of patients having viral load above the specific cutoff level of 6 x 105 was significantly high in those with CKD compared to those without CKD. This trend persisted with higher cut-off levels as well (Fig. 3).
On multivariate regression analysis, only higher age (P = 0.004; OR 1.06; 95% CI 1.01-1.10), hypertension (P = 0.02; OR 2.68; 95% CI 1.15-6.22), HCV
PCR[7 x 105 cps/mL (P = 0.01, OR 2.45; 95% CI 1.21-4.98), and DM (P = 0.02, OR 2.37; CI 1.14-4.91) were noted as significant independent positive predictors for CKD, whereas history of IFN treatment (P = 0.003; OR 0.18; 95% CI 0.06-0.56) was noted as significant independent negative predictor for CKD. Age, gender, HIV status, DM, IVDU, and HCV genotype were not predictors for CKD in this study.
Introduction
Many studies have implicated a potential role of hepatitis C virus (HCV) infection as a cause of chronic kidney disease (CKD). Chronic infection with HCV is known to cause glomerular diseases [1-3]. Using data from the Third National Health and Nutrition Examination Survey, two studies have found an increased risk of albuminuria in patients with hepatitis C [4, 5], and another study found an increased risk of developing end-stage renal disease (ESRD) [6]. The prevalence of serum positive for antibody to hepatitis C among CKD patients who were never transfused has been reported to be about ten times higher than that of blood donors [7]. The progression of diabetic nephropathy has been reported to be more rapid when patients were infected with HCV [8, 9], and other studies also found the presence of hepatitis C viral particles or antigens in glomeruli or tubules of kidney biopsy specimens [3, 10, 11]. Although these data support that hepatitis C may also cause CKD, conflicting data also exist [12].
We hypothesized that infection with HCV increases the risk of developing CKD and accelerates the progression to CKD. To test our hypothesis, we compared a cross section of hepatitis C positive patients with age-, race-, and sex-matched controls without known HCV infection. We retrospectively followed these populations from their first hospital visit until their last follow-up visit to assess the risk of developing CKD.
RESULTS
Prevalence of CKD in the study population
Estimation of CKD by creatinine method revealed 37 (6.7%) patients in the HCV group developed CKD compared to 11 (3.5%) in the control group without known
HCV infection (Pearson Chi-square, P = 0.05). When patients with proteinuria were also added to the patients with CKD by creatinine estimation method, 43 (7.8%) patients with serum positive for anti-HCV antibody could be categorized as having CKD compared to 13 (4.2%) controls (P = 0.04) (Fig. 1).
On a cross-sectional analysis based on the initial evaluation (first visit to the hospital), GFR<60 mL/min/1.73 m2 was noted in 16 (5.1%) of 314 controls compared to 26 (4.7%) of 552 anti-HCV-positive patients (P = 0.79). Nonspecific isolated elevation or acute renal failure accounted for the decline in GFR in 6 patients in the control group and 8 patients in the HCV group. Thus at the baseline, 10 (3.2%) of 314 controls compared to 18 (3.3%) of 554 had CKD by four-variable MDRD method (P = 0.96). Longitudinal analysis of serial GFR values until the last available follow-up or until the defined time
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