Recipient-donor race mismatch for African American liver transplant patients with chronic hepatitis C

African American (AA) recipient-donor race mismatch has been associated with graft loss and mortality, but studies of an association between race mismatch and hepatitis C virus (HCV) disease severity are lacking. HCV-infected adults from 4 US centers who underwent liver transplantation for the first time (n = 1093) were followed for a median of 3.05 years to determine the rates of advanced HCV disease (bridging fibrosis or cirrhosis) and graft failure; 11% of the patients were AA. The unadjusted cumulative rate of advanced fibrosis was higher in AAs than non-AAs (56% and 40% at 4 years, respectively, (P < 0.01), and 59% and 56% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P = 0.89). In adjusted models, both AA recipient race [hazard ratio (HR) = 1.47, 95% CI = 1.06-2.03, P = 0.02] and AA recipient-donor mismatch (versus match; HR = 1.48, 95% CI = 1.03-2.12, P = 0.03) were significant predictors of advanced fibrosis; other independent predictors were donor age (HR = 1.21, P < 0.01) and cytomegalovirus infection (HR = 1.55, P < 0.01). The 4-year unadjusted cumulative rates for HCV-associated graft loss were 10% and 17% for non-AAs and AAs, respectively (P < 0.01), and 0% and 21% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P < 0.01). In adjusted models, AA recipient-donor-mismatched patients had a 62% higher rate of graft loss than non-AA recipients (HR = 1.62, 95% CI = 1.14-2.29, P < 0.01), and AA recipient-donor-matched patients had a 76% lower rate of graft loss/mortality (HR = 0.24, 95% CI = 0.06-0.97, P = 0.05). In conclusion, AA recipient-donor-mismatched patients who are infected with HCV are at high risk for advanced HCV disease and HCV-related graft loss and constitute a patient group that will benefit from new therapeutic strategies for preventing graft loss.     

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.     

Improved survival with statins, angiotensin receptor blockers, and steroid weaning after heart transplantation

Various immunosuppressive and adjunctive pharmacological regimens exist for cardiac transplantation, though the associations between these regimens and long-term survival are unclear. We reviewed demographic, clinical, and pharmacological data from 220 consecutive adult heart transplant recipients between 1986 and 2003 who survived beyond 3 months. Immunosuppression was cyclosporine-based (n=94) or tacrolimus-based (n=126), and 104 patients were weaned off steroids (all receiving tacrolimus). Covariates of mortality were assessed in a Cox proportional hazards analysis. The mean age was 5.2+/-13 years. Survival was 96%, 88%, and 81% at 1, 3, and 5 years, respectively. Significant covariates associated with mortality included pretransplant diabetes mellitus (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.45 to 5.04), black race (HR 1.41, 95% CI 1.01 to 1.94), higher pretransplant creatinine clearance (HR 0.99, 95% CI 0.98 to 1.00), steroid withdrawal (HR 0.60, 95% CI 0.39 to 0.85), and exposure to a statin (HR 0.53, 95% CI 0.40 to 0.70) or an angiotensin receptor blocker (HR 0.50, 95% CI 0.20 to 0.95) after transplantation. Treatment with a statin, an angiotensin receptor blocker, and steroid withdrawal were each associated with improved survival in heart transplant recipients. These findings warrant prospective study, with specific emphasis on identifying the clinical effects of these medications in transplant recipients.     

Preemptive kidney transplantation in systemic lupus erythematosus

Preemptive kidney transplantation is associated with superior outcomes. Patients who have kidney failure due to systemic lupus erythematosus (SLE) may not receive a preemptive kidney transplant because of the concern for risk of disease recurrence with shortened graft and patient survival. We identified 8001 patients in the United Network for Organ Sharing dataset who underwent kidney transplantation between October 1987 and February 2009 with kidney failure due to SLE. Seven hundred thirty patients received a preemptive kidney transplant with 7271 patients who were on dialysis before transplantation; their mean ages were 40.0 ± 11.6 years and 36.9 ± 11.7 years, respectively, (P < .01). Women constituted 82.5% of preemptive and 81.4% of non-preemptive groups (P = .47). Preemptive transplant recipients were more likely to receive a living donor kidney transplant (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 3.3–4.5; P < .01). In unadjusted analyses, preemptive transplantation was associated with lower risk of recipient death (hazard ratio [HR] = 0.52; 95% CI = 0.38–0.70; P < .01). The difference remained significant after adjustment fr covariates (HR = 0.55; 95% CI = 0.36–0.84; P < .01). Graft survival was also superior among preemptive kidney transplant recipients in both unadjusted (HR = 0.56; 95% CI = 0.49–0.68; P < .01), and adjustment analyses (HR = 0.69; 95% CI = 0.55–0.86; P < .01). We concluded that preemptive kidney transplantation among patients with SLE was associated with superior patient and graft outcomes and should be considered when feasible.     

First case of toxoplasmosis following small bowel transplantation and systematic review of tissue-invasive toxoplasmosis following noncardiac solid organ transplantation

BACKGROUND: Toxoplasmosis prophylaxis is standard following heart and heart lung transplantation, when an increased risk of allograft transmitted Toxoplasma is well-recognized. In contrast, prophylaxis and routine serologic evaluation of donors and recipients for Toxoplasma in noncardiac solid organ transplantation (SOT) is not recommended. We report the first case of disseminated toxoplasmosis following small bowel transplantation, presumably transmitted via the transplanted intestine and systematically review reported cases of toxoplasmosis in noncardiac SOT recipients to determine if current guidelines should be reconsidered. METHODS: Systematic MEDLINE review was performed for tissue invasive toxoplasmosis in noncardiac SOT recipients and analysis of clinical features, serologic status, and treatment regimens with respect to mortality. RESULTS: Fifty-two cases of toxoplasmosis in noncardiac SOT recipients were identified. Eighty-six percent developed disease within 90 days of transplantation. Presentation was nonspecific and consisted of fever (77%), respiratory distress (29%), neurologic manifestations (29%), and bone marrow suppression (26%). Multivariate analyses demonstrated that localized disease (odds ratio [OR]=37.36, 95% CI 1.85-754.85), treatment received (OR=1.814, 95% CI 1.193-3.480) and donor and recipient serostatus (OR=1.39, 95% CI 1.068-1.815) were predictors of survival. High-risk recipients (donor seropositive/recipient seronegative) developed disease earlier (16 days vs. 31 days P=0.002) and were less likely to survive (OR=0.14, 95% CI 0.03-0.69) than standard-risk recipients. CONCLUSIONS: Toxoplasmosis is recognized following noncardiac SOT. Reduction of morbidity and mortality necessitates knowledge of donor and recipient Toxoplasma serostatus, prophylaxis, early diagnosis, and treatment. The findings support a reconsideration of pretransplantation evaluation and prophylaxis strategies in SOT recipients.     

Early posttransplant serum osteoprotegerin levels predict long-term (8-year) patient survival and cardiovascular death in renal transplant patients

The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.     

Risk factors for allograft failure in United kingdom renal transplant recipients treated with cyclosporine A

BACKGROUND: After the introduction of cyclosporine A (CsA), 2-year graft survival of transplanted kidneys improved from less than 60% to more than 80%, but long-term graft survival and graft half-life have shown less change. This study investigates the impact of a range of demographic and treatment factors on long-term graft survival in renal recipients treated with CsA from all renal transplant centers in the United Kingdom. METHODS: Data were obtained from the Long-Term Efficacy and Safety Surveillance study of renal transplant recipients receiving CsA (Neoral; Novartis, Basel, Switzerland). A total of 1,757 de novo patients with a functioning graft at 1 year were evaluated. The endpoints considered were the need for regular dialysis or death. A stepwise stratified Cox model was used to identify the factors associated with outcome. RESULTS: Seven independent risk factors for allograft failure were identified: older recipient (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.6), male recipient (HR 1.8, 95% CI 1.2-2.7), younger donor (HR 1.7, 95% CI 1.2-2.5), above average creatinine (HR 1.9, 95% CI 1.3-2.8), chronic allograft nephropathy (HR 7.0, 95% CI 4.7-10.4), diabetic recipient (HR 2.2, 95% CI 1.2-4.1), and neoplasm after transplant (HR 1.7, 95% CI 1.2-2.6). CONCLUSION: Seven independent risk factors were found to influence graft survival. Only two of these can be modified by clinical intervention, elevated serum creatinine at 1 year and the occurrence of chronic allograft nephropathy. To influence these two factors, the optimization of immunosuppressive therapy is essential.     

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case‐control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty‐eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38‐0.58), with the highest rate in lung (1.48, 95% CI 0.93‐2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29‐6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03‐10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15‐4.37; P = .02). These findings may help to improve the management of SOT recipients.     

Incidence of and Risk Factors for Posttransplant Diabetes Mellitus after Pancreas Transplantation

Posttransplant diabetes mellitus (PTDM) after pancreas transplantation (PTX) has not been extensively examined. This single center, retrospective analysis of 674 recipients from 1994 to 2005 examines the incidence of and risk factors for PTDM after PTX. PTDM was defined by fasting plasma glucose level ≥126 mg/dL, confirmed on a subsequent measurement or treatment with insulin or oral hypoglycemic agent for ≥30 days. The incidence of PTDM was 14%, 17% and 25% at 3, 5 and 10 years after PTX, respectively and was higher (p = 0.01) in solitary pancreas (PAN) versus simultaneous kidney pancreas (SPK) recipients (mean follow‐up 6.5 years). In multivariate analysis, factors associated with PTDM were: older donor age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.03–1.06, p < 0.001), higher recipient body mass index (HR 1.07,CI 1.01–1.13, p = 0.01), donor positive/recipient negative CMV status (HR 1.65,CI 1.03–2.6, p = 0.04), posttransplant weight gain (HR 4.7,CI 1.95–11.1, p < 0.001), pancreas rejection (HR 1.94.CI 1.3–2.9, p < 0.001) and 6 month fasting glucose (HR 1.01,CI 1.01–1.02, p < 0.001), hemoglobin A₁c, (HR 1.12,CI 1.05–1.22, p = 0.002) and triglyceride to high‐density lipoprotein (TG/HDL) ratio (HR 0.94,CI 0.91–0.96, p < 0.001). This study delineates the incidence and identifies risk factors for PTDM after PTX.     

The 90-Day Mortality After Pancreatectomy for Cancer Is Double the 30-Day Mortality: More than 20,000 Resections From the National Cancer Data Base

Background

Operative mortality traditionally has been defined as the rate within 30 days or during the initial hospitalization, and studies that established the volume–outcome relationship for pancreatectomy used similar definitions.

Methods

Pancreatectomies reported to the National Cancer Data Base (NCDB) during 2007–2010 were examined for 30- and 90-day mortality. Unadjusted mortality rates were compared by type of resection, stage, comorbidities, and average annual hospital volume. Hierarchical logistic regression models generated risk-adjusted odds ratios for 30- and 90-day mortality.

Results

After 21,482 pancreatectomies, the unadjusted 30-day mortality rate was 3.7 % (95 % confidence interval [CI] 3.4–3.9 %), which doubled at 90 days to 7.4 % (95 % CI 7.0–7.8). The unadjusted and risk-adjusted mortality rates were higher at 30 days with increasing age, increasing stage, male gender, lower income, low hospital volume, resections other than distal pancreatectomy, Medicare or Medicaid insurance coverage, residence in a Southern census division, history of prior cancer, and multiple comorbidities. The lowest-volume hospitals (<5 per year) performed 19 % of the pancreatectomies, with a risk-adjusted odds ratios for mortality that were 4.2 times higher (95 % CI 3.1–5.8) at 30 days and remained 1.9 times higher (95 % CI 1.5–2.3) at 30–90 days compared with hospitals that had high volumes (≥40 per year).

Conclusion

Mortality rates within 90 days after pancreatic resection are double those at 30 days. The volume–outcome relationship persists in the NCDB. Reporting mortality rates 90 days after pancreatectomy is important. Hospitals should be aware of their annual volume and mortality rates 30 and 90 days after pancreatectomy and should benchmark the use of high-volume hospitals.     

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma,Aspergillus Colonization,Invasive Aspergillosis and Death in Lung Transplant Recipients

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all‐cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04–2.88; p = 0.03), with each additional 30‐day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02–1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34–0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all‐cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13–0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient‐specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.     

C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease

BACKGROUND: High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. METHODS: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. RESULTS: Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. CONCLUSION: Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.     

Preventive Strategies Against Cytomegalovirus and Incidence of α‐Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella‐zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person‐years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5–5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7–14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2–4] versus 9.8% [95% CI 8.4–11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus‐positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.     

Mortality after kidney transplant failure: the impact of non-immunologic factors

BACKGROUND: One third of cadaveric kidney transplant recipients suffer graft loss within five years of transplantation. Non-immunologic factors that predict mortality among non-transplant patients also may be potentially modifiable risk factors for mortality among patients with transplant failure. METHODS: Applying multivariate survival analysis to data from the United States Renal Data System, we determined the effect of immunologic or transplant related factors and non-immunologic factors on mortality in patients who initiated dialysis after kidney transplant failure in the United States between April 1995 and September 1998. RESULTS: A total of 4741 patients were followed for a median +/- standard deviation of 15 +/- 11 months after initiation of dialysis after transplant failure. The majority of the 1016 (21%) deaths were due to cardiac (36%) or infectious (17%) causes. Patients in the following groups had an increased risk for all-cause mortality: older patients [hazard ratio (HR) = 1.04 per year, 95% confidence interval (95% CI) 1.03-1.04], women (HR = 1.31, 95% CI 1.10-1.56), patients of white race (HR = 1.94, 95% CI 1.32-2.84), patients with diabetes (HR = 1.76, 95% CI 1.43-2.16), peripheral vascular disease (HR = 1.94, 95% CI 1.54-2.43), congestive heart failure (HR = 1.26, 95% CI 1.05-1.53), drug use (HR = 2.23; 95% CI 1.08-4.60), smokers (HR = 1.35, 95% CI 1.01-1.81), first transplant recipients (HR = 1.32, 95% CI 1.02-1.69), and patients with a higher glomerular filtration rate (GFR) at dialysis initiation (HR = 1.04 per mL/min higher, 95% CI 1.02-1.06). Those with private insurance (HR = 0.67, 95% CI 0.49-0.93) and higher serum albumin (HR = 0.73 per g/dL higher, 95% CI 0.64-0.83) had a decreased risk for all-cause mortality. Acute rejection, antibody induction, donor source, duration of graft survival and the maximum attained GFR during transplantation did not predict all-cause mortality. CONCLUSIONS: Non-immunologic factors predicted mortality among patients with transplant failure but immunologic and transplant related factors did not. Prevention, early diagnosis and treatment of co-morbid conditions and the complications of chronic kidney disease may improve the survival of patients with transplant failure.     

Multivariate analysis of the effectiveness of using antibody induction therapy according to the degree of HLA mismatches

OBJECTIVE: HLA mismatches have a strong impact on acute rejection and renal allograft survival. The objective of this study was to evaluate the effectiveness of antibody induction according to the degree of HLA mismatches. METHODS: Of 20,429 deceased donor (DD) transplantations and 12,859 living donor (LD) transplantations reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% of DD and 45% of LD transplant recipients received induction therapy. Propensity scores (PS) were calculated to indicate independent factors associated with the use of induction. Levels of HLA match examined for DD transplant recipients were 0 ABDR (n = 3239), 0 DR (n = 4210), and DR mismatched transplants (n = 12,980), and 0 (n = 1133), 1 (n = 3836), and 2 (n = 7890) haplotype mismatches for LD transplant recipients. Outcome parameters were reported as hazard ratios (HR) for graft loss and odds ratios (OR) for first-year acute rejection. RESULTS: Recipients with HLA mismatches were more likely to receive induction antibody for DR mismatch in DDs (PS = 1.11, 95% confidence interval [CI] 1.04-1.19) and for haplotype mismatch in LDs (PS = 1.36, 95% CI 1.22-1.52). Induction reduced the likelihood of acute rejection for DD transplant recipients regardless of the level of HLA mismatch (OR = 0.70; 95% CI 0.57-0.85 in 0 ABDR MM; OR = 0.76, 95% CI 0.64-0.89 in 0 DR MM; and OR = 0.69, 95% CI 0.62-0.77 in DR MM), and for 2 haplotype mismatched LD transplant recipients (OR = 0.82, 95% CI 0.70-0.96); in other LD transplant recipients, reductions in acute rejection rates were observed but not statistically significant. Induction reduced the risk of graft loss for DR mismatched DD transplant recipients by about 12% (HR = 0.88; 95% CI 0.80-0.97). CONCLUSIONS: Antibody induction resulted in a significant reduction of acute rejection and graft loss for patients with HLA mismatch.     

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06–1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74–1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long‐term mortality (HR, 1.14; 95% CI 1.01–1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.     

Posttransplantation anemia at 12 months in kidney recipients treated with mycophenolate mofetil: risk factors and implications for mortality

Although posttransplantation anemia (PTA) is common in the mycophenolate mofetil era, its impact on patient survival is unknown. This retrospective cohort study characterized factors that are associated with PTA 12 mo after transplantation in mycophenolate mofetil-treated kidney recipients and explored whether 12-mo PTA affects outcomes. The records of 626 kidney recipients were examined for presence of anemia (hemoglobin <12 g/dl). Multivariate regression models, fit with covariates that had unadjusted relationships, investigated both risk factors for 12-mo PTA and whether 12-mo PTA contributes to mortality. Anemia prevalence was 72, 40, and 20.3% at 1, 3, and 12 mo, respectively. By multivariate logistic regression, anemia at 3 mo (odds ratio [OR] 10.0; 95% confidence interval [CI] 5.3 to 17.1; P = 0.0001), donor age (OR 1.0; 95% CI 1.1 to 1.3; P = 0.005), and 3-mo creatinine (OR 2.0; 95% CI 1.2 to 3.3; P = 0.044) were associated with 12-mo PTA. The PTA cohort had inferior patient survival (P = 0.02, log rank) and a higher proportion of cardiovascular deaths (6.3 versus 2.2%; P = 0.017) than nonanemic patients. By Cox regression, 12-mo PTA (hazard ratio [HR] 3.0; 95% CI 1.3 to 6.7; P = 0.009), 12-mo creatinine (HR 1.3; 95% CI 1.1 to 1.4; P = 0.008), age at transplantation (HR 1.1; 95% CI 1.1 to 1.2; P = 0.004), and hepatitis C seropositivity (HR 2.8; 95% CI 1.1 to 7.0; P = 0.03) were associated with mortality. There was no interaction between 12-mo PTA and serum creatinine. In conclusion, 12-mo PTA is associated with an increased risk for patient death. The presence of anemia 3 mo after kidney transplantation is a major determinant of 12-mo PTA. PTA in kidney recipients therefore should be defined by its persistence or occurrence beyond the third posttransplantation month.     

Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation.

With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.     

Incidence and Risk Factors for Cytomegalovirus Disease in a Colombian Cohort of Kidney Transplant Recipients

Incidence and risk factors for cytomegalovirus (CMV) disease in a Colombian cohort of kidney transplant recipients. CMV infection and disease are important causes of morbidity and mortality in kidney transplant recipients, and its prevalence varies with economic, geographic, and ethnic factors. Among 1620 records from a Colombian reference center, CMV immunoglobulin (Ig)G seroprevalence was found to be 90.9% among recipients and 90.2% among donors. In 86% (n = 264) of the cases, CMV disease occurred during the first 6 months after the transplantation, and the most frequent clinical presentation was CMV syndrome, followed by gastrointestinal disease. The following parameters were independent predictors of CMV disease: serological status of D+/R+ (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.03–2.63) and D+/R− (HR, 2.72; 95% CI, 1.49–4.93), age of the recipient (HR, 1.02; 95% CI, 1.01–1.03), and receiving more than 30 mg of prednisolone by the end of the first month after transplantation (HR, 1.59; 95% CI, 1.22–2.07). Acyclovir prophylaxis or other antiviral agents significantly decreased the risk of disease (HR, 0.41; 95% CI, 0.29–0.58 and HR, 0.34; 95% CI, 0.20–0.58, respectively). In conclusion, we found a high prevalence of CMV infection in a cohort of Latin American transplant recipients. In accord with findings from other regions, serological status is the main risk factor, prophylaxis with acyclovir is effective, and induction with alemtuzumab does not increase the risk of CMV disease.     

Death in the first year after kidney transplantation: implications for patients on the transplant waiting list

BACKGROUND: As the kidney transplant waiting list continues to expand, maintaining the medical fitness of transplant candidates will become increasingly difficult. METHODS: To identify patients who are at greatest risk during the wait-list period, we performed a Cox regression analysis to determine risk factors for mortality in the first posttransplantation year among 23,546 adult first kidney transplant recipients recorded in the United States Renal Data System between January 1995 and September 1997. RESULTS: In this study population, 4.6% of the patients died in the first posttransplantation year, and cardiac causes were the leading cause (27%) of death. Patients with diabetes (hazard ratio [HR]=1.58; 95% confidence interval [CI], 1.39-1.80), peripheral vascular disease (HR=1.41; 95% CI, 1.11-1.80), or angina (HR=1.38; 95% CI, 1.15-1.65), and patients with a longer duration of end-stage renal disease (HR=1.06 per year; 95% CI, 1.04-1.09) had a higher risk for mortality. Additionally, patients with early acute rejection (HR=1.47; 95% CI, 1.23-1.76), delayed graft function (HR=1.46; 95% CI, 1.25-1.71), and a lower glomerular filtration rate after transplantation were also at increased risk for death within the first posttransplantation year. CONCLUSIONS: Patients with comorbid disease, patients with a long duration of end-stage renal disease, and potential recipients of organs at high risk for graft dysfunction should be carefully screened for medical complications before transplantation to achieve the most favorable outcomes. Alternate organ allocation strategies that facilitate patient assessment close to the time of transplantation or that prioritize high-risk patients may also improve outcomes.