The Impact of Transplantation with Deceased Donor Hepatitis C-Positive Kidneys on Survival in Wait-Listed Long-term Dialysis Patients

Whether transplantation of deceased donor kidney allografts from donors with antibodies against hepatitis C virus (HCV) confers a survival advantage compared with remaining on the kidney transplant waiting list is not yet known. We studied 38,270 USRDS Medicare beneficiaries awaiting kidney transplantation who presented with end-stage renal disease from April 1, 1995 to July 31, 2000. Cox regression was used to compare the adjusted hazard ratios for death among recipients of kidneys from deceased donors, and donors with antibodies against hepatitis C (DHCV+), controlling for demographics and comorbidities. In comparison to staying on the waiting list, transplantation from DHCV+ was associated with improved survival among all patients (adjusted hazard ratio for death 0.76, 95% CI 0.60, 0.96). Of patients receiving DHCV+ kidneys, 52% were themselves hepatitis C antibody positive (HCV+), so outcomes associated with use of these grafts may have particular implications for HCV+ transplant candidates. Recommendations for use of DHCV+ kidneys may require analysis of data not currently collected from either dialysis or transplant patients. However, transplantation of DHCV+ kidneys is associated with improved patient survival compared to remaining wait-listed and dialysis dependent.     

Elderly recipients of hepatitis C positive renal allografts can quickly develop liver disease

Our institution explored using allografts from donors with Hepatitis C virus (HCV) for elderly renal transplantation (RT). Thirteen HCV- elderly recipients were transplanted with HCV+ allografts (eD+/R-) between January 2003 and April 2009. Ninety HCV- elderly recipients of HCV- allografts (eD-/R-), eight HCV+ recipients of HCV+ allografts (D+/R+) and thirteen HCV+ recipients of HCV- allografts (D-/R+) were also transplanted. Median follow-up was 1.5 (range 0.8-5) years. Seven eD+/R- developed a positive HCV viral load and six had elevated liver transaminases with evidence of hepatitis on biopsy. Overall, eD+/R- survival was 46% while the eD-/R- survival was 85% (P = 0.003). Seven eD+/R- died during follow-up. Causes included multi-organ failure and sepsis (n = 4), cancer (n = 1), failure-to-thrive (n = 1) and surgical complications (n = 1). One eD+/R- died from causes directly related to HCV infection. In conclusion, multiple eD+/R- quickly developed HCV-related liver disease and infections were a frequent cause of morbidity and mortality.     

Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool?

INTRODUCTION: Because the disparity between the number of patients waiting for kidney transplants and the number of available cadaveric renal allografts continues to increase, there is a clear need to review the inclusion criteria for cadaveric donors. PATIENTS AND METHODS: From January 2001 to March 2004, 24 patients with end-stage renal disease and hepatitis C virus (HCV) seropositivity underwent a kidney transplantation. In 10 transplants in HCV-positive recipients, the donor was HCV-positive (D+/R+) and in 14 cases the donor (1 living donor) was HCV-negative (D-/R+). RESULTS: Two of 3 HCV-RNA-negative recipients who received a HCV-RNA+ kidney became HCV-RNA+ in the posttransplantation period. There was a low rate of acute rejection (8.3%). One D+/R+ patient experienced an acute vascular rejection, which finally resulted in graft loss, due to the resurgence of severe infectious disease. The serum creatinine levels at 6 months posttransplantation were similar in both groups. Acute liver dysfunction was observed in 1 patient. There was no death in the entire series. Graft survival was 92% and 90% for D+/R+ and D-/R+, respectively.     

Hepatitis C and renal transplantation in the era of modern immunosuppression

Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.     

Pancreas transplantation from hepatitis C viremic donors to uninfected recipients

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.     

Long-term results of CMV hyperimmune globulin prophylaxis in 377 heart transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) has emerged as the most important pathogen to affect the post-operative course after heart transplantation. We performed a retrospective analysis to evaluate the efficiency of CMV hyperimmune globulin (CMVIG) prophylaxis in preventing CMV disease in aggressively immunosuppressed patients after heart transplantation. METHODS: We studied 377 heart transplant recipients who received quadruple-immunosuppressive therapy and CMVIG as sole CMV prophylaxis. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D+/R+, D+/R-, D-/R+, D-/R-) and was monitored for CMV immediate early antigen in peripheral blood cells, in urine sediments, and in throat washings; for the presence of serum CMV immunoglobulin M and CMV immunoglobulin G; and for clinical evidence of CMV-related symptoms. In addition, we compared the incidence of cardiac allograft vasculopathy and infection among the groups. RESULTS: During the first 5 years after transplantation, CMV disease developed in 79 patients (20.96%). Comparison among the groups showed significantly increased risk for CMV disease in allograft recipients of organs from seropositive donors (D+, 27.31%; D-, 11.33%; p = 0.0003). We observed 6 CMV-associated deaths, all in CMV-antibody-negative recipients. Additionally CMV-positive recipients had a greater incidence of cardiac allograft vasculopathy (p = 0.048), and a greater overall infection rate (p = 0.0034). CONCLUSIONS: Cytomegalovirus hyperimmune globulin administration prevents CMV disease and infection in aggressively immunosuppressed heart transplant recipients. Because fatal CMV disease in CMV-negative recipients of organs from seropositive donors could not be prevented with CMVIG alone, we recommend the additional use of prophylactic ganciclovir in this CMV-mismatched population.     

Impact of hepatitis B core antibody status on outcomes of cadaveric renal transplantation: analysis of United network of organ sharing database between 1994 and 1999.

BACKGROUND: Organ shortage continues to be a major problem in transplantation. The use of organs from marginal donors who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc Ab) reactive (+), could increase the donor pool substantially. Little information is available about the effects of anti-HBc Ab (+) donor status on viral transmission, and graft and patient survival. To address these issues, an analysis was performed using the United Network of Organ Sharing cadaveric kidney transplant database between 1994 to 1999. METHODS: All cadaveric kidney transplants performed between 1994 to 1999 with negative HBsAg serology were evaluated. Viral transmission, and graft and patient outcomes were measured. The analysis included follow-up information in the United Network of Organ Sharing database through September 2000. A multivariate analysis was performed, using known confounding factors that may affect the outcomes in donors and recipients who were designated as (+) or (-) (D+/R+, ++D+/R-, D-/R-, and D-/R+) according to their anti-HBc Ab status. RESULTS: Univariate analyses showed that graft and patient survival rates were statistically significantly lower in D+/R- compared with those who were D-/R-. However, multivariate regression analyses showed that neither donor nor recipient anti-HBc Ab status influenced the risk of graft failure or patient death after adjustment for other factors. Anti-HBc Ab (+) kidneys resulted in a higher incidence of anti-HBc antibody seroconversion but this was not associated with a higher incidence of HBsAg detection. CONCLUSION: We conclude that renal allografts from anti-HBc Ab (+) donors should be considered for transplant especially in successfully immunized recipients.     

Kidney transplantation from donors with viral B and C hepatitis

INTRODUCTION: The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our experience in transplanting kidneys from donors with hepatitis B virus (HBV) or hepatitis C virus (HCV) among matched serology-positive recipients. MATERIALS AND METHODS: From January 2002 to November 2005, 44 patients with end-stage renal disease and HCV seropositivity underwent kidney transplantation. In 28 transplants in HCV+ recipients, the donor was HCV+ (DC+/RC+) and in 16 of these cases the donor (one living donor) was HCV- (DC-/RC+). In the same period 14 patients with HBV infection and HbsAg seropositivity underwent kidney transplantation: eight received their graft from a cadaveric HbsAg-positive donor (DB+/RB+), while six patients received their graft from an HbsAg-negative donor. RESULTS: Viral reactivation was higher among DC+/RC+ (21.4%) than DC-/RC+ patients (6%). Graft survivals were 90% and 88% for DC+/RC+ and DC-/RC+, respectively; patient survivals were 100% for DC+/RC+ and 94% for DC-/RC+. Among the group of DB+/RB+, all the patients developed an HBV-DNA positivity in the early postoperative period. Patient and graft survivals were 100% in both groups. CONCLUSIONS: Our results suggest that HBV- and HCV-positive donors can be considered as an alternative donor source, because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.     

The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience

Singh N, Neidlinger N, Djamali A, Leverson G, Voss B, Sollinger HW, Pirsch JD. The impact of hepatitis C virus donor and recipient status on long‐term kidney transplant outcomes: University of Wisconsin experience. Abstract: The survival benefit of transplanting hepatitis C (HCV)‐positive donor kidneys into HCV‐positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV‐status of the donor (D) kidney on the long‐term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased‐donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D?/R? (n = 1897), D?/R+ (n = 59), D+/R? (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox‐proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted‐hazard ratio [HR] 2.1, 95% CI [1.4–2.9]) with respect to the reference D?/R? group, whereas mortality was not increased in D?/R+ group. The rate of graft loss was increased in both D+/R+ and D?/R+ but was comparable with each other (adjusted‐HR 1.8, 95% CI [1.4–2.5]) vs. adjusted‐HR 2.0, 95% CI [1.4–2.8], respectively). D?/R+ cohort experienced significantly higher rate of rejection (adjusted‐HR 1.7, 95% CI [1.2–2.5]) and chronic allograft nephropathy (adjusted‐HR 2.1, 95% CI [1.2–3.7]). Neither donor nor recipient HCV‐status impacted the risk of recurrent or de novo GN. Transplanting HCV‐positive kidneys as opposed to HCV‐negative kidneys into HCV‐positive recipients provided similar graft survival but compromised patient survival in the long term.     

Multivariate analysis of the influence of donor and recipient cytomegalovirus sero-pairing on outcomes in simultaneous kidney-pancreas transplantation: the South-Eastern Organ Procurement Foundation Experience

The purpose of this study was to determine if donor (D) and recipient (R) CMV sero-pairing at the time of simultaneous kidney-pancreas transplantation (SKPT) subsequently influenced outcomes in a large cohort of patients with long-term follow-up. Between January 1, 1997 and December 31, 1999 complete data were available on 723 primary SKPTs performed at South-Eastern Organ Procurement Foundation member institutions. For purposes of this study, four groups were defined: D+/R-, n = 203 (28%); D+/R+, n = 206 (28%); D-/R+, n = 156 (22%); and D-/R-, n = 158 (22%). Patient and graft survival rates for the study groups were computed by Kaplan-Meier estimates and tests of equality of survival curves were performed utilizing both the log-rank and Wilcoxon test statistics. A multivariate analysis was performed using a Cox proportional hazards model and logistic regression. A total of 56% of Ds were CMV+ and 50% of Rs were CMV-. D serostatus was not, but R serostatus was, a significant independent risk factor for patient and kidney, but not pancreas, graft survival rates in the uncensored analysis. When examining the CMV D/R groups in both univariate and multivariate fashion, CMV sero-pairing was not an independent risk factor for death, graft loss, or rejection. However, when considering CMV sero-pairing as a binary variable (D-/R- versus all other D/R groups), 6-year patient, kidney, and pancreas graft survival rates were significantly higher in the D-/R- group (P < .05). In conclusion, CMV seronegativity is present in half of diabetic patients at the time of SKPT, and protective CMV seronegative matching confers a long-term survival advantage.     

Who among cytomegalovirus-seropositive liver transplant recipients is at risk for cytomegalovirus infection?

A vast majority of the transplant recipients are cytomegalovirus (CMV)-seropositive (R+). We sought to assess variables predictive of CMV infection, specifically in R+ liver transplant recipients. Study patients comprised 182 consecutive liver transplant recipients who survived at least 14 days after transplantation. Surveillance testing was used to detect CMV infection. Pre-emptive therapy was employed for the prevention of CMV disease, however, no antiviral prophylaxis was used for CMV infection. CMV infection developed in 32.5% (38 of 117) of R+ patients, 84.6% (33 of 39) of R-/D+, and 3.8% (1 of 26) of R-/D- patients. In R+ patients, Hispanic race (21.6% vs. 7.8%, P = 0.06), donor CMV seropositivity (73.7% vs. 45.6%, P = 0.005), and hepatocellular carcinoma (23.7% vs. 6.3%, P = 0.05) correlated with a higher risk of CMV infection. In a multivariate model, Hispanic race (OR: 3.5, 95% CI: 1.03-11.6, P = 0.045), donor CMV serostatus (OR: 4.0, 95% CI: 1.6-10.2, P = 0.003) and hepatocellular carcinoma (OR: 5.8, 95% CI: 1.6-20.5, P = 0.006) were all significant independent predictors of CMV infection. The aforementioned variables did not portend a higher risk of CMV infection in R-/D+ patients; donor CMV seropositivity overwhelmed all other risk factors in R- patients (P < 0.00001). In conclusion, CMV-seropositive liver transplant recipients at risk for CMV infection can be identified based on readily assessable variables. Preventive strategies may be selectively targeted toward these patients.     

Center‐level trends in utilization of HCV‐exposed donors for HCV‐uninfected kidney and liver transplant recipients in the United States

Several single‐center reports of using HCV‐viremic organs for HCV‐uninfected (HCV‐) recipients were recently published. We sought to characterize national utilization of HCV‐exposed donors for HCV‐ recipients (HCV D+/R?) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015‐December 2, 2018) and Gini coefficients, we studied center‐level clustering of 1193 HCV D+/R? KTs and LTs. HCV‐viremic (NAT+) D+/R? KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV‐aviremic (Ab+/NAT‐) D+/R? KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV‐ recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2‐1.6) and 1.6 (0.4‐3.5) years on the waitlist versus 1.8 (0.5‐4.0) among HCV D?/R?. HCV‐ recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21‐30) and 25 (21‐32) at transplantation versus 29 (23‐36) among HCV D?/R?. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R? transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R? transplants. There have been marked increases in HCV D+/R? transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R? transplantation.     

Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine. Interim results of a randomized controlled trial

We report the interim results of a randomized, double-blind, placebo-controlled, clinical trial of prophylactic, live, attenuated cytomegalovirus (CMV) vaccination (Towne strain of CMV) of renal transplant candidates (RTCs). One hundred seventy-two RTCs were treated and subsequently underwent transplantation and followed up for at least one year and up to five years after transplantation. Eighty-eight RTCs received vaccine, and 84 received placebo. Results were analyzed according to the prevaccination serologic status (anti-CMV antibody titer) of the recipient (R- or R+) and the donor (D- or D+). The overall incidence of CMV disease was highest in the R-D+ group and almost absent in the R-D- group. There was no difference in the incidence of CMV infection or disease between vaccinated and respective placebo control recipients in either the R-D+, R+D+, R+D-, or R-D- groups. In contrast, the severity of CMV disease was significantly decreased in R-D+ vaccinees vs R-D+ placebo-treated recipients. Moreover, in the R-D+ group, one- and five-year cadaver renal allograft actuarial survival rates were 73% and 62%, respectively, for CMV vaccinees vs 40% and 25%, respectively, for control placebo patients. We conclude that seronegative cadaver RTCs may benefit from vaccination with live, attenuated, Towne strain CMV vaccine before transplantation.     

Risk factors and impact of cytomegalovirus disease in simultaneous pancreas-kidney transplantation.

BACKGROUND: The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis. METHODS: This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R-) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R-) SPK transplant recipients was also evaluated. RESULTS: The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D-/R+: 0%; D-/R-: 2.8%; D+/R+: 25.6%; and D+/R-: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P=0.0052). In the high-risk (D+/R-) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival. CONCLUSIONS: Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed.     

Prediction and diagnosis of cytomegalovirus disease in renal transplant recipients using qualitative and quantitative polymerase chain reaction

BACKGROUND: Preemptive antiviral therapy against cytomegalovirus (CMV) disease after transplantation requires information from suitable laboratory markers. We examined the use of qualitative and quantitative polymerase chain reaction (PCR) to monitor renal transplant recipients. METHODS: A cohort of 77 renal transplant recipients was monitored using an in-house and a commercial (Amplicor; Roche Diagnostic, Basel, Switzerland) PCR on leukocytes and plasma. Quantitative plasma viral load was determined using a commercial PCR kit (CMV Monitor; Roche Diagnostic). Patients were analyzed according to their pretransplantation CMV serological status (R- or R+). RESULTS: Seventeen patients developed CMV disease after transplantation. Qualitative leukocyte PCRs had the best overall sensitivity (54-69%) and specificity (75-87%) in identifying R- recipients with CMV disease before onset. The specificities of qualitative PCRs for R+ recipients were poor and, if used, could result in unnecessary preemptive treatment in up to 50% of patients. Symptomatic and asymptomatic R+, but not R-, recipients could be distinguished using a plasma viral load of 25,000 copies/ml. An increase in viral load of >0.7 log (fivefold) per week also distinguished between symptomatic and asymptomatic R+ recipients with high sensitivity (100%) and specificity (95%). CONCLUSIONS: Qualitative leukocyte PCRs were the best assays to predict CMV disease for R- recipients who received R+ kidneys. None of the qualitative assays could be used to guide preemptive therapy of R+ recipients, but plasma viral load and its incremental rate could be used as diagnostic tools in R+ recipients.     

Effect of donor-recipient cytomegalovirus serologic status on outcomes in simultaneous kidney-pancreas transplant recipients

Diabetic patients undergoing simultaneous kidney-pancreas transplantation (SKPT) may be at high risk for developing cytomegalovirus (CMV) infection. To study this issue, we analyzed 297 SKPT patients enrolled into a multicenter trial of two daclizumab dosing strategies versus no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids. Complete donor (D) and recipient (R) CMV serology values were available in 294 cases and were distributed as follows: 86 (29%) D+/R-. Eighty-six (29%) D+R+; 45 (16%) D-/R+; 77 (26%) D-/R-; CMV antiviral prophylaxis was center specific, but 98% of patients received either ganciclovir or acyclovir. No differences existed in demographic or transplant characteristics or immunosuppressive regimens among the four groups except that more African-American SKPT recipients were CMV positive at transplant (P <.001). At 6 months, no differences were seen in patient and graft survival rates (GSR) and the incidence of acute rejection (AR) among the groups. However, the CMV D+/R- group had a significantly higher incidence of CMV infection/disease (14%) than the other groups collectively (4%, P <.05). Most cases of CMV infection/disease occurred greater than 3 months posttransplant when prophylaxis was discontinued. In the D-/R- group, the pancreas GSR was higher (94% vs 86% in the remaining three groups) and the incidence of AR was lower (16% vs 25% in the remaining three groups, both P =.09). Primary CMV exposure remains a major risk factor for CMV infection/disease, but does not have an adverse impact on short-term outcomes. Conversely, protective CMV seronegative matching may have a beneficial effect on outcomes.     

Relationship of hepatitis B or C virus prevalences, risk factors, and outcomes in renal transplant recipients: analysis of German data

BACKGROUND: Chronic liver disease resulting from hepatitis B (HBV) and hepatitis C (HCV) virus infections is still a major concern in kidney recipients. Our aim was to evaluate the prevalences, risk factors, and impact of HBV and HCV infections in adult renal transplant recipients in Germany. MATERIALS AND METHODS: Data were collected on 1633 kidney recipients transplanted between 1989 and 2002 at the 21 German renal transplant centers participating in MOST, the prospective Multinational Observational Study in Transplantation. Subgroup analyses compared HBV- and HCV-positive patients vs those with HBV/HCV-negative serology at the time of transplantation. RESULTS: The prevalences of 4.4% (n = 72) for HBV and 5.8% (n = 94) for HCV showed a marked decline over the last 15 years. Retransplantations were significantly more common among HBV+ (29%) and HCV+ (36%) than HBV-/HCV- patients (12%). HCV+ patients experienced significantly longer dialysis times and received significantly more pretransplantation blood transfusions. Between all groups, no significant differences were observed in acute rejection rate at 12 months or in renal graft function up to 5 years posttransplantation (mean glomerular filtration rate: HBV+, 57.3 mL/min; HCV+, 58.5 mL/min; HBV-/HCV-, 59 mL/min). No progressive elevations in liver enzymes and bilirubin were noted during the 5-year observation period. CONCLUSIONS: HBV and HCV infections currently have a low prevalence among German kidney graft recipients. Long dialysis times, blood transfusions, and retransplantations were identified as risk factors for hepatitis infections. At 5 years posttransplantation, kidney and liver functions did not differ significantly between HBV+ and HCV+ vs HBV-/HCV- renal transplant recipients.     

Posttransplant diabetes mellitus in renal transplant patients with hepatitis C virus

The aim of this study was to assess the possible association between posttransplant diabetes mellitus (DM) and hepatitis C virus (HCV) infection in renal transplant recipients. This study included 124 patients who underwent renal transplantation between 1997 and 2002. Inclusion criteria were patients who were not diabetic prior to transplantation and posttransplant follow-up longer than 6 months. DM was defined as fasting blood glucose levels higher than 126 mg/dL on at least two occasions. HCV infection was detected using second- or third-generation ELISA methods and/or polymerase chain reactions for HCV-RNA. Twenty-five HCV positive (HCV+) patients were compared with 25 consecutive HCV negative (HCV-) transplant patients. Demographic and clinical data of the groups were compared. Posttransplantation DM was observed in 24% of the HCV+ patients. There were no statistical differences in age, gender, race, family history of DM, follow-up, or body mass index between the two groups. There was a higher prevalence of posttransplantation DM in HCV+ patients, but the difference did not reach statistical significance (24% vs 12%, P = NS). Alternatively, comparing patients of the two groups (n = 50) who did versus not develop DM, the incidence of posttransplantation DM was higher among HCV+ patients, but the difference did not reach statistical significance (66.6% vs 46.3%, P = NS). In conclusion, there was no association between HCV infection and the development of posttransplantation DM in this cohort of renal transplant recipients. However, there was a trend that suggested an association.     

Cytomegalovirus infection and development of biliary complications after liver transplantation

BACKGROUND: Cytomegalovirus (CMV) infection is known to cause ulceration and mucosal hemorrhage in the gastrointestinal tract. Gastroduodenal and biliary complications were prospectively evaluated in 100 consecutive liver transplant patients in whom CMV was monitored during the first posttransplant year. METHOD: Gastroduodenal biopsy specimens were taken from 36 patients by endoscopies and in 28 patients by endoscopic retrograde cholangiopancreatography, and bile duct specimens were taken from three patients who underwent surgical reconstruction because of biliary complication. CMV was demonstrated from blood by the pp65 antigenemia test and from frozen sections of tissue specimens by immunohistochemistry and in situ hybridization. RESULTS: Symptomatic CMV infection, treated with ganciclovir, developed in 49 recipients: 13 (100%) of CMV seropositive donor (D+) seronegative recipient (R-) cases, 29 (45%) D+/R+ cases, and 7 (32%) D-/R+ cases. Duodenal ulcer developed in three and hemorrhagic gastritis in three recipients. CMV antigens were found from the gastroduodenal mucosa in 37 (69%) of the 54 studied recipients. The biliary complication rate was 24%. Preceding or concomitant CMV antigenemia was demonstrated in 75% of patients with a biliary complication (68% in CMV D+/R+ or D-/R+ and 100% in D+/R- recipients). The biliary complication rate was higher among recipients with CMV antigenemia, compared with recipients without (P<0.05). CMV antigenemia, CMV infection, or both in the duodenal mucosa was found in 96% of patients with a biliary complication. In two patients who underwent surgical reconstruction, CMV antigens and DNA were demonstrated in the bile ducts. CONCLUSIONS: Liver transplant patients are at risk of developing biliary complications after CMV infection, especially those with primary CMV infection.     

肾移植术后巨细胞病毒感染的选择性防治方案

目的 探讨根据受者风险状态采取预先治疗策略防治肾移植术后巨细胞病毒(CMV)感染的有效性和安全性.方法 60例肾移植患者随机分为普遍预防治疗组(普遍预防组)和预先控制治疗组(预先控制组),每组30例.两组肾移植术后均接受14 d的基础治疗(静脉滴注更昔洛韦250 mg/d),随后普遍预防组继续口服更昔洛韦,至术后90 d;预先控制组中的高危患者继续口服更昔洛韦,直至术后90 d,中危患者中仅CMV pp65抗原阳性者静脉滴注更昔洛韦,至CMV pp65抗原转阴后停药,低危患者在基础治疗后不再使用更昔洛韦.研究期为6个月,期间监测两组患者的CMV pp65抗原和CMV DNA,以及血常规、尿常规、肝功能、肾功能和排斥反应发生情况.结果 普遍预防组13例(43.3%,13/30)出现抗原血症,有5例(16.7%,5/30)的CMV DNA载量持续升高,其中1例(3.3%,1/30)发展成为CMV病.预先控制组14例(46.7%,14/30)出现抗原血症,有4例(13.3%,4/30)的CMV DNA载量持续升高,其中2例(6.7%,2/30)发展为CMV病.普遍预防组和预先控制组急性排斥反应发生率分别为16.7%(5/30)和6.7%(2/30);其它感染总的发生率分别为16.7%(5/30)和20%(6/30).两个组6个月时的人、肾存活率均为100%,其血肌酐的差异也无统计学意义(P＞0.05).结论 根据受者风险状态采取预先治疗策略能有效防治肾移植术后CMV感染,其效果与普遍预防策略相当.