Hepatitis C Virus and Death Risk in Hemodialysis Patients
Kamyar Kalantar-Zadeh*,,
Ryan D. Kilpatrick*,,
Charles J. McAllister,
Loren G. Miller||,
Eric S. Daar¶,
David W. Gjertson,
Joel D. Kopple,** and
Sander Greenland
* Harold Simmons Center for Kidney Disease Research and Epidemiology, and Divisions of Nephrology and Hypertension, || Infectious Disease, and ¶ HIV Disease, Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, and David Geffen School of Medicine at UCLA, Torrance, Departments of Epidemiology, Biostatistics, and ** Community Health, School of Public Health, University of California Los Angeles, Los Angeles, and (8) DaVita, Inc., El Segundo, California
Address correspondence to: Dr. Kamyar Kalantar-Zadeh, Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910. Phone: 310-222-3891; Fax: 310-782-1837; E-mail: kamkal{at}ucla.edu
Received for publication July 14, 2006.
Accepted for publication March 1, 2007.
In maintenance hemodialysis (MHD) patients, hepatitis C virus(HCV) infection is common and may be associated with poor clinicaloutcomes. It was hypothesized that HCV infection would be associatedwith high all-cause and cardiovascular mortality in these patientsafter controlling for demographic and clinical characteristics,including surrogates of malnutrition-inflammation complex syndrome.A national database of 13,664 MHD patients who underwent HCVantibody serology testing at least once during a 3-yr interval(July 2001 through June 2004) was analyzed. Measurements includedthird-generation HCV enzyme immunoassay and routine laboratorymeasurements. The HCV enzyme immunoassay was reported positivein 1590 (12%) patients. In logistic regression models that includedcase mix and available surrogates of malnutrition-inflammationcomplex syndrome, HCV infection was associated with youngerage, male gender, black race, Hispanic ethnicity, Medicaid insurance,longer dialysis vintage (duration), unmarried status, HIV infection,and smoking history. In proportional-hazards regressions, themortality hazard ratio that was associated with HCV infectionwas 1.25 (95% confidence interval 1.12 to 1.39; P < 0.001).Mortality hazards were higher among incident (dialysis duration<6 mo) than prevalent HD patients. Subgroup analyses indicatedthat HCV was associated with higher all-cause and cardiovascularmortality across almost all clinical, demographic, and laboratorygroups of patients. Hence, in MHD patients, HCV infection exhibitsdistinct demographic, clinical, and laboratory patterns, includingassociations with higher dialysis treatment vintage, and isassociated with higher mortality. More diligent efforts to preventand treat HCV infection may improve outcomes in MHD patients.
Hepatitis C virus (HCV) infection is the most common cause ofchronic liver disease in the world (1). Certain populations,including maintenance hemodialysis (MHD) patients, have a significantlyhigher prevalence of HCV infection, ranging from 5 to 25% oreven higher, according to the recent literature (2–5).This population may serve as an exceptional model to study theimpact of HCV infection on outcomes, especially because theshort-term death risk is extremely high in MHD patients in theUnited States, at least 20% annually (6). Several investigationshave suggested that HCV infection is associated with highermortality in this population (7–12), but these studieshave been limited in size and selectivity, the largest comprisingonly 367 HCV-infected patients (11). Given that HCV-associatedliver disease typically takes decades to become clinically manifest,a period of time much longer than the lifespan of most dialysispatients with a 5-yr survival of 60 to 70% (6), the liver disease–relatedcomplications seem the unlikely link to the high death risk.
Approximately half of all deaths in MHD patients are attributedto cardiovascular disease (13). To date, associations betweentraditional cardiovascular risk factors and death have not beenobserved in MHD patients (14,15), but a strong association betweenelements of the malnutrition-inflammation complex (or cachexia)syndrome (MICS) and poor clinical outcome has been observed(16). Because HCV infection is associated with increases ininflammatory markers and alterations in nutritional status inboth the general population (17–19) and dialysis patients(20) and is related to poor survival in MHD patients, examiningassociations between HCV infection and death risk after adjustmentfor markers of MICS may better reveal the mechanisms that leadto mortality that is associated with HCV infection. Moreover,a larger study population allows more detailed examination ofdiverse subgroups and potential interactions.
We studied a large national database of MHD patients in theUnited States to examine the hypothesis that HCV antibody–positiveMHD patients have a higher risk for all-cause and cardiovascularmortality. We also examined whether HCV-infected MHD patientshave distinct demographic, clinical, and laboratory characteristicsthat can be used to screen for HCV infection.
Patients
Data from all individuals who had ESRD and underwent MHD treatmentfrom July 2001 to June 2004 in one of the 580 outpatient dialysisfacilities of a large dialysis organization (DaVita, Inc.) inthe United States were extracted and examined. The study wasapproved by the institutional review committees of both LosAngeles Biomedical Research Institute at Harbor-UCLA and DaVitaClinical Research, and the requirement for written consent formfor individually identifiable data was waived on he basis ofthe Standards for Privacy of Individually Identifiable HealthInformation (21).
Clinical and Demographic Measures
For minimization of measurement variability, all repeated measuresfor each patient during any given calendar quarter (i.e., duringa 13-wk interval) were averaged, and the summary estimate wasused in all models. Hence, average values were obtained forup to 12 calendar quarters (q1 through q12) for each laboratoryand clinical measure for each patient during the 3-yr cohortperiod. MHD status was defined as HD treatment during at least45 consecutive days. Dialysis vintage was defined as the durationof time between the first day of dialysis treatment and thefirst day that the patient entered the cohort. For preexisting(prevalent) MHD patients (i.e., dialysis vintage 6 mo), datafrom the first calendar quarter (July through September 2001)were used. For new (incident) patients (i.e., dialysis vintage<6 mo), the baseline values originated from the calendarquarter in which the patient had undergone MHD for at least45 d at the start of the given calendar quarter.
Thirteen-week averaged postdialysis weight and baseline heightwere used to calculate the body mass index (BMI; weight [kg]/heightsquared [m2]). The dosage of administered recombinant humanerythropoietin (rHuEPO; EPOGEN; Amgen, Thousand Oaks, CA) wasalso calculated for each calendar quarter (22–24). Causesof death, reflecting the reported information in the Cause ofDeath form (Form 2746 for reporting to the US Renal Data System[USRDS]), were obtained. Cardiovascular death was defined asdeath as a result of myocardial infarction, cardiac arrest,heart failure, cerebrovascular accident, and other cardiac causes.Infectious death was defined as death attributed to an infectiousdisease as the primary cause of death.
In addition to the presence or absence of diabetes, which wasavailable a priori in the database, histories of tobacco smokingand preexisting comorbid conditions were obtained by linkingthe DaVita database to the Medical Evidence Form 2728 of theUSRDS (25) and categorized into 10 comorbid conditions: (1)Ischemic heart disease, (2) congestive heart failure, (3) statuspost cardiac arrest, (4) status post myocardial infarction,(5) pericarditis, (6) cardiac dysrhythmia, (7) cerebrovascularevents, (8) peripheral vascular disease, (9) chronic obstructivepulmonary disease, and (10) cancer.
Laboratory Measures
Blood samples were drawn using uniform techniques in all ofthe DaVita dialysis clinics and were transported to the DaVitaLaboratory in Deland, FL, typically within 24 h. All laboratoryvalues were measured by automated and standardized methods inthe DaVita Laboratory. Most laboratory values, including completeblood cell counts and hemoglobin and serum levels of urea nitrogen,creatinine, albumin, calcium, phosphorus, bicarbonate, and totaliron-binding capacity (TIBC), were measured monthly. Serum ferritinwas measured quarterly. Hemoglobin was measured weekly to biweeklyin most patients. Kt/V was used to estimate dialysis dosage,and normalized protein equivalent of total nitrogen appearance,also known as normalized protein catabolic rate, an estimationof daily protein intake, was measured monthly as a measure ofprotein intake. Most blood samples were collected before dialysiswith the exception of the postdialysis serum urea nitrogen,which was obtained to calculate urea kinetics. The HCV antibodystatus was examined using the third generation of the HCV enzymeimmunoassay (EIA version 2.0; Abbott Laboratories, Abbott Park,IL).
Statistical Analyses
In addition to standard descriptive statistics, multiple logisticregression models were fitted to estimate odds ratios of HCVinfection controlling for potentially confounding covariates.Survival analyses included Kaplan-Meier and log-rank tests andtime-dependent Cox proportional hazard regressions, using repeatedmeasures of all laboratory values, rHuEPO dosage, and BMI ascovariates. We examined whether the 3-yr survival rates wereassociated with HCV infection, which was assumed to be presentboth retrospectively and prospectively when at least one HCVEIA test was positive. For each analysis, three models wereexamined on the basis of the level of multivariate adjustment:
An unadjusted model that included mortality data, HCV antibodyresult (positive versus negative), and entry calendar quarter(q1 through q12).
Case mix–adjusted models that includedall in 1 plus age,gender, race, and ethnicity (African Americanand other self-categorizedblack, non-Hispanic white, Asian,Hispanic, and other), diabetesand 10 preexisting comorbid states,history of tobacco smoking,categories of dialysis vintage (<6mo, 6 mo to 2 yr, 2 to5 yr, and 5 yr), primary insurance (Medicare,Medicaid, private,and other), marital status (married, single,divorced, widowed,and other or unknown), the standardized mortalityratio of thedialysis clinic during entry quarter, dialysisdosage as indicatedby Kt/V (single pool), presence or absenceof a dialysis catheter,and residual renal function during theentry quarter (i.e.,urinary urea clearance).
MICS-adjustedmodels, which included all of the covariates inthe case-mixmodel as well as 13 surrogates of nutritional statusand inflammation,including BMI, the average dosage of rHuEPO,and 11 laboratoryvariables as surrogates of the nutritionalstate or inflammation,together also known as MICS, with knownassociation with clinicaloutcomes in MHD patients (26–28):(1) Normalized proteinequivalent of total nitrogen appearanceas an indicator of dailyprotein intake, (2) serum albumin,(3) serum TIBC, (4) serumferritin, (5) serum creatinine, (6)serum phosphorus, (7) serumcalcium, (8) serum bicarbonate,(9) peripheral white blood cellcount, (10) lymphocyte percentage,and (11) hemoglobin.
Missing covariate data (<2% for most laboratory and demographicvariables and <18% for the 10 comorbid conditions) were imputedby the mean or median of the existing values as appropriate.All descriptive and multivariate statistics were carried outwith SAS (version 9.1; SAS Institute, Cary, NC) and Stata (version9.0; Stata Corp., College Station, TX).
Because hepatitis serology tests are usually performed beforea patient is accepted to an outpatient dialysis clinic for maintenancedialysis treatment, many patients with a previously documentedHCV EIA result in outside facilities did not undergo repeatHCV EIA test in DaVita dialysis clinics. In this study, we examinedonly HCV EIA tests that were performed in the DaVita Laboratoryafter a patient was admitted for MHD and only patients who remainedunder MHD treatment for at least 45 d. The original 3-yr (July2001 through June 2004) national database of all DaVita patientsincluded 82,933 individuals (source population) who had undergoneMHD treatment for at least 45 d including 37,049 (45%) patientsfrom the first calendar quarter and the rest from the subsequent11 quarters. During each of the 12 calendar quarters, the presenceof HCV antibody was examined in 4 to 9% of all MHD patientsof the given calendar quarter using the EIA test in the DaVitaLaboratory. Cumulatively, in 13,664 MHD patients, or 16% ofall DaVita MHD patients, including 5828 (42%) from the firstcohort quarter, at least one HCV EIA test was performed. Amongthese HCV-tested patients, 1590 (12%) MHD patients had at leastone positive HCV EIA test, including 48 patients with discordantresults (i.e., at least one positive and one negative results).The remaining 12,074 MHD patients had concordant HCV antibody–negativeresults. Between 2001 and 2004, the annual prevalence of HCVEIA positivity among MHD patients whose HCV test was performedin DaVita Laboratory showed only small variations: 12.2% in2001, 11.4% in 2002, 11.5% in 2003, and 11.1% in 2004.
Table 1 shows baseline demographic, clinical, and laboratorycharacteristics of the studied MHD patients during the baselinecalendar quarter of the cohort. HCV-positive patients were onaverage 7 yr younger and more likely to be men than either theHCV-negative or the entire cohort population. Black patientscomposed 53% of all HCV-positive patients while constitutingonly slightly less than one third of HCV-negative patients.The prevalence of Medicaid insurance status among HCV-positivepatients was 70% higher than in other groups. Diabetes and cardiovasculardiseases were less prevalent in HCV-infected patients, but deathas a result of cardiovascular disease was only slightly lessso. History of smoking and of HIV disease was at least twiceas common in HCV-infected patients compared with other patients.Among laboratory parameters, serum albumin was slightly lowerbut TIBC and creatinine were higher in HCV-positive patientscompared with HCV-negative patients. Serum levels of three routinelymeasured liver enzymes (aspartate aminotransferase [AST], lactatedehydrogenase, and alkaline phosphatase) were higher in HCV-infectedpatients, with AST almost twice as high in HCV-positive patientsas in HCV-negative patients. Nevertheless the mean value inHCV-positive patients was 29 IU/L, which is still within the"normal" range of most commercial assays.
Table 1. Demographic, clinical, and laboratory characteristics in 82,958 MHD patients, including 69,294 patients without any HCV testing in the central laboratory and 13,664 MHD patients who were tested for the presence of HCV antibodya
With the use of logistic regressions, the association betweendemographic, clinical, and laboratory characteristics and HCVpositivity was examined among all 13,664 MHD patients who haddocumented HCV EIA test results (Table 2). Younger age (<65yr), single marital status, black race, history of HIV disease,and tobacco smoking each were associated with at least two timeshigher odds of HCV positivity. Among laboratory measures, serumAST was the strongest predictor of HCV infection.
Table 2. Conditions associated with HCV antibody in 13,664 MHD patientsa
Because the longer dialysis vintage could be associated withHCV infection, additional analysis of vintage were conducted.The relative prevalence for the logarithm of vintage (in dialysismonths) was 1.36 (95% confidence interval 1.28 to 1.43; P <0.001). Upon further categorization of the dialysis vintageinto seven groups (<3 mo, >10 yr, and five groups in between)and using the 3- to 6-mo group as the reference, higher vintagegroups >6 mo were incrementally associated with higher prevalenceof HCV infection across increasing vintage categories (Figure 1).
Figure 1. Association between time on dialysis (vintage) and hepatitis C virus (HCV) infection prevalence in 13,664 maintenance hemodialysis (MHD) patients during 3 yr (July 2001 through June 2004).
Among 13,664 HCV-tested patients, 5659 (41%) survived untilthe end of the cohort (June 30, 2004) or up to 1095 d; 3584(26%) died; 934 (7%) underwent renal transplantation; and 3487(26%) were censored as a result of transfer to a non–DaVitafacility, relocation, discontinuation of MHD, and other lossesto follow-up. The HCV-tested cohort included 23,390 patient-years,including 2814 patient-years for HCV-positive and 20,576 patient-yearsfor HCV-negative patients with median cohort time of 638 and619 d, respectively; 3130 (25.9%) HCV-negative and 454 (28.6%)HCV-positive patients died during the 3-yr cohort. Table 3 showsthe unadjusted (crude) death rates among incident and prevalentHCV-positive and HCV-negative patients during the first 1000d of the MHD cohort. The unadjusted mortality ratio among incidentpatients was incrementally increased from 1.15 to 1.84 overtime. Table 4 shows the all-cause mortality hazard ratios associatedwith HCV infection from three multivariate adjustment levelsusing Cox proportional hazards regression. HCV infection wasmore strongly associated with death in incident patients (vintage<6 mo) than in prevalent patients (vintage 6 mo). Figure 2compares cumulative proportion of surviving incident and prevalentpatients according to HCV status during the 3-yr cohort, adjustedfor age, gender, race, and diabetes. A stronger associationbetween HCV infection and mortality was observed in incidentpatients compared with prevalent patients. Figure 3 shows hazardratios of all-cause and cardiovascular death in various subgroupsof MHD patients. All-cause and cardiovascular death hazardsare similar, although confidence intervals are wider for cardiovascularhazards as a result of smaller death numbers.
Figure 2. Kaplan-Meier cumulative proportion of surviving patients for all-cause mortality according to HCV antibody positivity in MHD patients during 3 yr adjusted for age, gender, race, and diabetes. (Top) All patients (n = 13,664). (Middle) Incident patients with a dialysis vintage <6 mo (n = 5129). (Bottom) Prevalent patients with a dialysis vintage 6 mo (n = 8535). Adjusted mortalities are lower than the unadjusted mortalities, and the y axis depicts only the upper portion of the entire range of survival percentage.
Figure 3. Hazard ratio of death associated with HCV infection in various subgroups of 13,664 dialysis patients during 3 yr. (Left) All-cause mortality. (Right) Cardiovascular mortality.
In 13,664 MHD patients who underwent the HCV EIA test and whoseoutcomes were observed over 3 yr, 12% showed a positive HCVantibody at least once. In logistic regressions that adjustedfor demographic and clinical characteristics and available surrogatesof malnutrition and inflammation, predictors of HCV includedyounger age, male gender, black race, Hispanic ethnicity, Medicaidinsurance, unmarried status, HIV positivity, and smoking history.The longer an MHD patient underwent HD since the start of dialysistreatment, the higher was the prevalence of HCV infection. HCVinfection was associated with both all-cause and cardiovascularmortality among MHD patients. This association was strongerin incident than in prevalent MHD patients, which may underscorethe effect of survival bias in the prevalent MHD patient cohort,many members of which had died before the start of the study.The association between HCV infection and mortality seemed consistentamong various subgroups of MHD patients and independent of causeof death.
HCV infection is much more common among MHD patients comparedwith the general population (2–4). Even though the prevalenceof positive HCV serology is said to be decreasing to levelsof the predialysis patient population, (8) this study indicatesa prevalence of 12% among those whose HCV antibody status wasscreened in one laboratory via the EIA during the 2001 to 2004period. Although a selection bias might exist in choosing MHDpatients for the HCV screening, we believe that most patientswho never had any HCV EIA tests are most likely those who hada negative HCV test result at baseline performed in a non–DaVitafacility or before the intercept of the 3-yr cohort. Our foregoingassertion is supported by the finding that most demographic,clinical, and laboratory features, including liver enzymes,were very similar among the 12,074 HCV antibody–negativepatients and the rest of the 69,294 patient cohort who did nothave a documented HCV EIA test (Table 1).
The striking discrepancy in prevalence of HCV infection betweenMHD patients and the general population may not be necessarilyrelated to the renal disease, because HCV infection seems morecommon in MHD patients compared with those who undergo peritonealdialysis, a renal replacement therapy with less blood exposure(2). Other studies have indicated increasing prevalence of HCVinfection with greater duration of MHD treatment (2,5,12) andcontinuing incidence of new HCV infections in MHD patients (29),suggesting that infection control efforts in dialysis centersmay be insufficient. Consistent with the latter findings, ourstudy also showed that dialysis treatment vintage was associatedwith higher HCV infection prevalence (see Figure 1). Althoughthis may be related to more cumulative risk of exposure to infectioussources over time, the possibility of a cohort effect shouldalso be considered (i.e., patients whose dialysis treatmentstarted in previous years had higher risk for HCV infectionas a result of less stringent HCV infection control measuresin the past [2,5]).
In our study, HCV infection was more strongly associated withmortality in incident MHD patients with a dialysis vintage <6mo when compared with prevalent MHD patients (see Figure 2 andTables 3 and 4). This finding may be due to a survival biasamong prevalent MHD patients, especially because the mortalityrate is 21% per year (30). Hence, our estimates of HCV-associatedmortality may be conservative (i.e., the true association betweenHCV infection and short-term risk for death in MHD patientsmay indeed be higher than that observed in prevalent cohorts).However, a cohort effect may also have led to these contrasts.Future studies are needed to examine these hypotheses.
In our investigation, as in others, the EIA was assumed as thereference standard of the HCV infection, and HCV-positive statuswas assumed to hold both prospectively and retrospectively whenat least one EIA test was positive. These assumptions may notbe correct if seroconversion occurred during the cohort time.Indeed, in 48 (3%) patients of our cohort, discrepant resultswere noticed, indicating lack of certainty about HCV infectionstatus. Furthermore, EIA testing may underestimate HCV prevalencein dialysis patients, some of whom may not develop anti-HCVantibody at least in early stages of HCV infection as a resultof relative state of immune deficiency (20). Molecular-basedassays that detect HCV RNA, such as PCR and transcription-mediatedamplification, are somewhat more sensitive diagnostic testsand may pick up additional HCV-infected patients (20,31). Hence,it is likely that the true prevalence of the HCV infection inour population is higher than that detected by the EIA test;misclassification of a small proportion of EIA-negative butHCV-infected patients may have introduced some bias in our estimates,most likely toward the null.
Our study indicated that HCV infection is more common amongyounger MHD patients, especially those from minority racialand ethnic backgrounds (Tables 1 and 2). More than half of HCV-infectedpatients in our study were black. In another observational studyof dialysis patients who underwent renal transplantation, HCVinfection was also found to be higher in black patients (3).These findings may be due to socioeconomic effects, rather thana direct effect of race, as reflected by higher prevalence ofMedicaid insurance among HCV-positive patients. The associationof HIV with HCV is perhaps not surprising, given that it sharessome mechanisms of transmission with HCV, whereas the smokingassociation is of less clear origin. We observed a paradoxicreduced prevalence of cardiovascular disease in HCV-infectedpatients despite their higher mortality, including as a resultof cardiovascular disease; this paradox may be due to the youngerage and lower prevalence of diabetes in HCV-infected MHD patients.Additional studies are needed to confirm and explain these relationships.
A key finding in our study was the higher short-term all-causeand cardiovascular mortality rate among virtually all subgroupsof HCV-infected MHD patients (see Table 4 and Figure 3). Atleast four other dialysis cohorts have exhibited an associationof HCV with mortality (7–10), but all were of relativelylimited size, and their findings may have not been applicableto the larger population of patients. Our original hypothesisthat this association could be due to MICS in HCV-positive patientswas only partially confirmed, because serum albumin, a surrogateof visceral protein, was lower, but TIBC and creatinine, othernutritional surrogates, were paradoxically higher in HCV-infectedpatients compared with HCV-negative individuals. However, directmarkers of inflammation and MICS, such as proinflammatory cytokines,were not available in our cohort. After adjustment for 13 availablesurrogates of MICS, the association between HCV infection andmortality was reduced in some subpopulations, which may indicatethat MICS is either a confounder or may be at least partiallyin the causal pathway (20,32). Hence, at least among some MHDpatients, HCV may be associated with poor survival and highershort-term cardiovascular death through yet-to-be-determinedfactors such as MICS.
Our study confirms some of the results that we recently reportedfrom analyzing a limited number of patients of the same cohort(11). The latter study, however, included only 367 HCV-infectedpatients, was limited to the baseline calendar quarter and only2 yr of follow-up, did not include time-dependent repeated measures,lacked information on history of comorbidity and smoking, anddid not include subgroup analyses because of small sample size(11). A limitation of this study is potential misclassificationof the cause of death as cardiovascular. Hence, all-cause deathmay be a more reliable outcome than cause-specific mortality.Another limitation of our analysis is that it is based on a3-yr period of the cohort, rather than longitudinal follow-upsover many years. Nonetheless, our results indicate that evenshort-term all-cause and cause-specific mortality is high inHCV-infected MHD patients. More elaborate and sensitive HCVdetection tests such as molecular tests (20) were not used inour study, because such methods are substantially more costlyand usually not used as screening tests. However, all laboratorymeasurements are performed in one single facility, and mostdata are means of several measures. Hence, measurement variabilityis minimized.
Perspective
Despite reported reductions in the prevalence of HCV infectionin dialysis populations in such countries as Spain (8), Italy(12), and Greece (33), which have had HCV prevalences much higherthan those in the United States, the HCV infection rate amongNorth American dialysis patients does not seem to have changedconsiderably. Regardless of its wide range of prevalence variationamong various countries (29), the associations between HCV infectionand increased death risk in dialysis patients seem consistent(7–12). Because dialysis patients have an exceptionallyhigh short-term mortality, it is less likely that the HCV-associateddeath risk is due to such long-term HCV complications as liverdisease. Inflammation associated with chronic infections (17–19)may contribute to the increased death risk in these individuals(20,32). The currently conservative approach to HCV-infecteddialysis patients (not treating them unless they have activeliver pathology) may need to be revisited in light of findingsthat link HCV infection to short-term death. More diligent effortsto prevent infection in dialysis clinics may be warranted.
Our results may have implications not only in the managementof HCV infection in dialysis patients but in many other individualswithout renal failure. More studies are needed to verify thetrue prevalence of HCV infection in the 21st century among dialysispatients in various countries using newer molecular testingto understand better the natural course of HCV infection andits link to short-term mortality and to evaluate the effectivenessof current and future anti-HCV treatment modalities in improvingclinical outcome in dialysis patients.
This study was supported by grants from the philanthropist HaroldSimmons, the American Heart Association (0655776Y), NationalInstitute of Diabetes and Digestive and Kidney Diseases (DK61162),and DaVita (to K.K.-Z.) and the National Institute of Allergyand Infectious Diseases (AI01831 to L.G.M.).
Some results were presented in abstract form during the annualconference of the National Kidney Foundation; April 19 to 22,2006; Chicago, IL.
K.K.-Z. contributed to the design of the study, collation andanalysis of data, and writing of the manuscript and its revisions.R.D.K., L.G.M., and E.S.D. contributed to the analysis of thedata and reviewed and approved the final manuscript. C.J.M.,J.D.K., and S.G. contributed to the design of the study, provisionof data, and final review and approval of the manuscript.
Footnotes
Published online ahead of print. Publication date availableat www.jasn.org.
Parts of these data were supplied by the USRDS, and the findingsdo not necessarily represent the opinion of the US governmentor the USRDS.
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[Abstract][Full Text][PDF]
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Abstract
Introduction
6 mo), data from the first calendar quarter (July through September 2001) were used. For new (incident) patients (i.e., dialysis vintage <6 mo), the baseline values originated from the calendar quarter in which the patient had undergone MHD for at least 45 d at the start of the given calendar quarter. 
