Does reduction in mycophenolic acid dose compromise efficacy regardless of tacrolimus exposure level? An analysis of prospective data from the Mycophenolic Renal Transplant (MORE) Registry

Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus‐treated patients: 375 (43.1%) reduced tacrolimus (≤7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus (>7 ng/mL); enteric‐coated mycophenolate sodium 589 (67.7%) and mycophenolate mofetil 281 (32.3%). During baseline to month 1, months 1–3, months 3–6, and months 6–12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535) patients, respectively, required MPA dose changes. These patients experienced an increased risk of biopsy‐proven acute rejection at one yr with tacrolimus exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28–5.29, p = 0.008) or excluded (HR 2.58, 95% CI 1.28–5.23, p = 0.008). MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included (HR 2.23; 95% CI 1.01–4.89, p = 0.047) but not when tacrolimus exposure was excluded (HR 2.16; 95% CI 0.99–4.79; p = 0.054). These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels.     

Donation after Cardiac Death Liver Transplantation: Predictors of Outcome

We aimed to identify recipient, donor and transplant risk factors associated with graft failure and patient mortality following donation after cardiac death (DCD) liver transplantation. These estimates were derived from Scientific Registry of Transplant Recipients data from all US liver‐only DCD recipients between September 1, 2001 and April 30, 2009 (n = 1567) and Cox regression techniques. Three years post‐DCD liver transplant, 64.9% of recipients were alive with functioning grafts, 13.6% required retransplant and 21.6% died. Significant recipient factors predictive of graft failure included: age ≥ 55 years, male sex, African–American race, HCV positivity, metabolic liver disorder, transplant MELD ≥ 35, hospitalization at transplant and the need for life support at transplant (all, p ≤ 0.05). Donor characteristics included age ≥ 50 years and weight >100 kg (all, p ≤ 0.005). Each hour increase in cold ischemia time (CIT) was associated with 6% higher graft failure rate (HR 1.06, p < 0.001). Donor warm ischemia time ≥ 35 min significantly increased graft failure rates (HR 1.84, p = 0.002). Recipient predictors of mortality were age ≥ 55 years, hospitalization at transplant and retransplantation (all, p ≤ 0.006). Donor weight >100 kg and CIT also increased patient mortality (all, p ≤ 0.035). These findings are useful for transplant surgeons creating DCD liver acceptance protocols.     

The role of pre-emptive re-transplant in graft and recipient outcome.

BACKGROUND: The effect of the pre-emptive re-transplant, and of inter-transplant waiting time generally, on graft and recipient survival is not well established. METHODS: Analysis of the United States Renal Data System (USRDS) data (1/1/90 through 12/31/00; n = 92,844) was performed. Cox regression was used to analyse time to event, with an additional analysis to stratify by transplant era. RESULTS: Having a prior transplant, as well as the total number of transplants, was related to an increased risk of graft failure [hazard ratio (HR) 1.24, P<0.001 for history of prior transplant; HR 1.35 per transplant, P<0.001], but not to recipient death. The time waiting for re-transplant slightly worsened the risk for recipient mortality in the entire patient population and in the recipients of single re-transplant (HR 1.003 and 1.004 per month respectively, P<0.001), and for graft failure only in recipients of single re-transplant (HR 1.001 per month, P<0.05). Pre-emptive re-transplant (dialysis-free re-transplant or transplant within 6 days of last graft failure) increased the risk of graft failure (HR 1.36, P<0.001) and did not have any statistically significant effect on recipient survival. The longer duration of prior graft survival but not the type of the graft (living vs deceased) had protective effect on the consecutive graft and recipient survival. CONCLUSIONS: With the potential caveats associated with retrospective data analysis, these results suggest that pre-emptive re-transplantation is associated with increased risk of graft failure, while longer time on dialysis in between transplants is associated with negative effect upon graft and recipient survival in most patient subgroups. The optimal time in between graft failure and re-transplant was not evaluated in this study. Further prospective studies might be needed to confirm the observed effects.     

The association between recipient alcohol dependency and long-term graft and recipient survival.

BACKGROUND: The causative role of alcohol consumption in renal disease is controversial, and its effect on renal graft and recipient survival has not been previously studied. METHODS: We analysed the association between pre-transplant [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and renal graft and recipient survival. The United States Renal Data System (USRDS) records of kidney transplant recipients 18 years or older transplanted between 1 January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis and Cox regression models adjusted for covariates to analyse the association between pre-transplant alcohol dependency and graft and recipient survival. RESULTS: In an entire study cohort of 60 523, we identified 425 patients with a history of alcohol dependency. Using Cox models, alcohol dependency was found to be associated with increased risk of death-censored graft failure [hazard ratio (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency with recipient survival and death-censored graft survival in males (but not in females), and in both white and non-white racial subgroups. CONCLUSIONS: We concluded that alcohol dependency at the time of ESRD onset is a risk factor for renal graft failure and recipient death.     

The impact of CMV prevention on long-term recipient and graft survival in heart transplant recipients: analysis of the Scientific Registry of Transplant Recipients (SRTR) database

The association between cytomegalovirus immunoglobulin (CMVIG) and long-term clinical outcomes in heart transplantation has not been evaluated using data from large national databases. We examined the association between CMVIG, with and without antivirals, or antivirals alone, and long-term recipient and graft survival in heart transplantation using data from the Scientific Registry of Transplant Recipients. Recipients transplanted between January 1995 and October 2008, ≤80 yr old, of primary, single-organ heart transplants, recorded as receiving CMVIG with or without antivirals (n = 2112), antivirals without CMVIG (n = 12 089), or no prophylaxis (n = 14 661), at hospital discharge, were included. Kaplan-Meier analysis was used to examine death and graft loss at seven yr post-transplantation; Cox proportional hazards regression was used to estimate the adjusted risk of graft loss and death for prophylaxis vs. no prophylaxis. CMVIG use (± other antivirals) was associated with increased recipient (69% vs. 64%, p < 0.001) and graft (67% vs. 63%, p < 0.001) survival. Antivirals alone also demonstrated increased recipient (68% vs. 64%, p < 0.001) and graft survival (66% vs. 63%, p < 0.001). Cox models demonstrated that CMVIG (± other antivirals) was independently associated with decreased risk for death (hazard ratio, HR 0.79, p < 0.001) and graft loss (HR 0.78, p < 0.001) as were antivirals alone (mortality HR: 0.79, p < 0.001; graft loss: HR 0.78, p < 0.001).     

Daclizumab is associated with decreased rejection and improved patient survival in renal transplant recipients

The present study investigated the safety of induction therapy with daclizumab (compared with no induction treatment), in adult renal transplant patients reported to the Scientific Registry of Transplant Recipients (SRTR) database between January 1, 1998 and July 27, 2003. Patients who were discharged from the hospital on mycophenolate mofetil, azathioprine, or sirolimus were divided into two groups: induction treatment with daclizumab (n = 8203) and no induction treatment (n = 25,368). Patient survival, death due to infection and death due to malignancy were evaluated at 1 and 3 yr post-transplantation. Rejection and graft survival were also examined. Kaplan-Meier and Cox regression models were used to evaluate outcomes. No significant differences were found between patients treated with daclizumab compared with patients who received no induction therapy for death due to infection or malignancy at 1 and 3 yr post-transplantation. Patients treated with daclizumab (compared with no induction treatment) had statistically significantly better survival rates at 1 (96.9% vs. 96.2%, p = 0.003) and 3 yr (92.4% vs. 91.4%, p = 0.004) although absolute differences were minimal. This was confirmed in the multivariable Cox regression analysis for patient death at 1 (HR = 0.77, p < 0.001) and 3 yr (HR = 0.83, p = 0.001) post-transplantation. Patients treated with daclizumab compared to no induction had lower rejection rates at 1 (13.1% vs. 17.3%, p < 0.001) and 3 yr post-transplantation (16.7% vs. 21.3%, p < 0.001). Cox regression confirmed a decreased risk for rejection at 1 (HR = 0.74, p < 0.001) and 3 yr (HR = 0.75, p < 0.001). Treatment with daclizumab was associated with reduced risk for graft loss at 1 (HR = 0.82, p < 0.001) and 3 years (HR = 0.86, p < 0.001). In conclusion, daclizumab was associated with a significantly reduced risk for rejection and graft loss compared with no induction treatment, and improved patient survival. In addition, daclizumab was not associated with an increase in risk of death due to infection or malignancy, when compared with no induction therapy. These findings demonstrate the short and long-term safety and efficacy of daclizumab in patients transplanted between January 1998 and July 2003.     

The impact of employment status on recipient and renal allograft survival

Abstract: Background:  With the improved median survival of kidney transplant recipients, there has been an increased focus on quality of life after transplantation. Employment is a widely recognized component of quality of life. To date, no study has demonstrated a link between post-transplant employment status and recipient and allograft survival after transplant.
Methods:  The records from the United States Renal Data System (USRDS) and the United Network for Organ Sharing (UNOS) from January 1, 1995, through December 31, 2002, were examined in this retrospective study. Two outcomes, allograft survival time (time between the transplantation and allograft failure or censor) and recipient survival time (time between the transplantation and recipient death or censor), were analyzed using Cox models adjusted for potential confounding factors.
Results:  Compared to patients working full time at the time of transplantation, those not working by choice have a greater risk to graft [hazard ratio (HR) 1.27, p < 0.001] but not to recipient survival. A similar trend was observed in patients not working at 12 months post-transplant (HR 1.30, p < 0.001 for graft survival but not for recipient survival). However, at five-yr post-transplant not working by choice was protective to the graft (HR 0.47, p < 0.01) as compared to working full time. Results of the analysis in the patient subgroups based on the comorbidities and the overall health status were similar.
Conclusion:  Employment status at the time of transplantation and in post-transplant period has a strong and independent association with the graft and recipient survival. Full time employment at the time of transplant and at one-yr post-transplant is associated with lower risk for graft failure and recipient mortality. However, working beyond the time covered by Medicare might be associated with potential risk for graft survival.     

Living donor age and kidney transplant outcomes: an assessment of risk across the age continuum

Detailed data on living donor age, and its interplay with recipient age, in predicting allograft and recipient outcomes are wanting. We used the Scientific Registry of Transplant Recipients (2000–2009, n = 49 589) to assess the effect of living donor age on delayed graft function (DGF), total graft failure, death‐censored graft failure, death with graft function, and graft failure with death as a competing risk using logistic and Cox proportional hazards models. Potential nonlinear associations were modeled using fractional polynomial functions. There was a significant 1.87‐fold increase in the adjusted odds of DGF in the oldest versus youngest age groups. The 10‐year adjusted hazard ratios (HR) for total graft failure, death‐censored graft failure, and death with graft function increased in a nonlinear fashion across the range of living donor age studied. Graft failure was most accentuated in the youngest recipient age groups in competing risk models. Adjustment for renal function at 6‐ and 12‐months post‐transplant markedly attenuated the association between living donor age and graft/patient outcomes. Our findings confirm the important influence of living donor age on transplant outcomes and provide detailed estimates of risk across the living donor age continuum.     

Education is associated with reduction in racial disparities in kidney transplant outcome

In this study, we hypothesized that higher level of education might be associated with reduced racial disparities in renal transplantation outcomes. We used data from the United States Renal Data System (September 1, 1990–September 1, 2007) (n = 79 223) and analyzed two outcomes, graft loss and recipient mortality, using Cox models. Compared with whites, African Americans had increased risk of graft failure (HR, 1.48; p < 0.001) and recipient mortality (HR, 1.06; p = 0.004). Compared with recipients who graduated from college, all other education groups had inferior graft survival. Specifically, compared with college‐graduated individuals, African Americans who never finished high school had the highest risk of graft failure (HR, 1.45; p < 0.001), followed by high school graduates (HR, 1.27; p < 0.001) and those with some college education (HR, 1.18; p < 0.001). A similar trend was observed in whites. In African Americans (compared with whites), the highest risk of graft failure was associated with individuals who did not complete high school (HR, 1.96; p < 0.001) followed by high school graduates (HR, 1.47; p < 0.001), individuals with some college education (HR, 1.45; p < 0.001), and college graduates (HR, 1.39; p < 0.001). A similar trend was observed with recipient mortality. In sum, higher education was associated with reduced racial disparities in graft and recipient survival.     

Anemia Is Associated with Mortality in Kidney-Transplanted Patients—A Prospective Cohort Study

Although anemia is a known risk factor of mortality in several patient populations, no prospective study to date has demonstrated association between anemia and mortality in kidney-transplanted patients. In our prospective cohort study (TransQol-HU Study), we tested the hypothesis that anemia is associated with mortality and graft failure (return to dialysis) in transplanted patients. Data from 938 transplanted patients, followed at a single outpatient transplant center, were analyzed. Sociodemographic parameters, laboratory data, medical history and information on comorbidity were collected at baseline. Data on 4-year outcome (graft failure, mortality or combination of both) were collected prospectively from the patients' charts. Both mortality and graft failure rate during the 4-year follow-up was significantly higher in patients who were anemic at baseline (for anemic vs nonanemic patients, respectively: mortality 18% vs. 10%; p < 0.001; graft failure 17% vs 6%; p < 0.001). In multivariate Cox proportional hazard models the presence of anemia significantly predicted mortality (HR = 1.690; 95% CI: 1.115-2.560) and also graft failure (HR = 2.465; 95% CI: 1.485-4.090) after adjustment for several covariables. Anemia, which is a treatable complication, is significantly and independently associated with mortality and graft failure in kidney-transplanted patients.     

Cyclosporine versus Tacrolimus Treated Liver Transplant Recipients with Chronic Hepatitis C: Outcomes Analysis of the UNOS/OPTN Database

Recurrent hepatitis C virus (HCV) remains a problematic cause of morbidity and mortality for liver transplant patients. Immunosuppression including calcineurin‐inhibitors has been implicated in the acceleration of recurrent HCV. Recent studies suggest that outcomes may be better with cyclosporine (CSA‐ME) compared to tacrolimus (TAC), but the data are inconclusive. We retrospectively analyzed data received from the United Network for Organ Sharing on 8809 chronic HCV liver transplant recipients receiving either cyclosporine microemulsion (CSA‐ME) or tacrolimus (TAC) as maintenance immunosuppression prior to discharge. We analyzed patient death, graft failure, failure due recurrent disease and acute cellular rejection (ACR) for CSA‐ME versus TAC treated patients. Three‐year unadjusted patient and graft survival rates were 76.8% and 71.5%, respectively, in the CSA‐ME group versus 79.9% and 75.0% in the TAC group. Propensity score‐adjusted results suggest CSA‐ME treated patients are at increased risk of patient death and graft failure [Hazards ratio (HR) = 1.17; 95% CI = 1.01–1.36 and HR = 1.19; 95% CI = 1.04–1.35, respectively] and biopsy‐confirmed AR (HR = 2.03; 95% CI = 1.54–2.67) compared to TAC treated patients. These results provide evidence to reconsider the targeted administration of CSA‐ME to HCV‐infected liver transplant recipients.     

Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre-transplant diabetes

Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)-treated renal transplant patients with pre-transplant diabetes. Outcomes were compared between MMF- (n = 14 144) and AZA- (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan-Meier survival analysis, Cox multivariable regression and chi-square tests. MMF patients had less AR compared with AZA-treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any-cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies.     

Mycophenolate mofetil combination therapy improves long-term outcomes after liver transplantation in patients with and without hepatitis C.

To evaluate the impact of mycophenolate mofetil (MMF) on long-term outcomes of tacrolimus and corticosteroids, we analyzed data reported to the Scientific Registry of Transplant Recipients for 11,670 adult patients (3463 with hepatitis C [HCV]) who underwent primary, single-organ, liver transplantation between 1995 and 2001. Patients who were discharged from the hospital on tacrolimus-based immunosuppression with (n = 4466; n = 1323 HCV) or without MMF (n = 7204; n = 2140 HCV) were included in the analysis. Recipients treated at discharge with MMF, tacrolimus, and corticosteroids had significantly increased patient survival (81.0% vs. 77.0% at 4 years, P < 0.0001) and graft survival (76.4% vs. 72.9%, P < 0.0001), and lower rates of acute rejection (29.0% vs. 33.4%, P < 0.001) as compared to recipients treated at discharge with tacrolimus and corticosteroids alone. A trend toward lower rates of death from infection was observed (6.1% at 4 years for MMF vs. 7.1% at 4 years for tacrolimus and corticosteroids, P = 0.0508), but this result did not reach statistical significance. In multiple regression analyses, MMF triple therapy at discharge was associated with a reduced risk of death (hazard ratio [HR] = 0.77, P < 0.001), graft loss (HR = 0.81, P < 0.001), acute rejection (HR = 0.89, P = 0.002), and death from infectious complications (HR = 0.80, P = 0.007). Outcomes were similar for the cohort with HCV.In conclusion, the addition of MMF at discharge to tacrolimus-based immunosuppression is associated with improved long-term outcomes after liver transplantation in patients with and without HCV.     

Diabetes Mellitus after Kidney Transplantation in the United States

New onset diabetes is a major complication after kidney transplantation. However, the incidence, risk factors and clinical relevance of post-transplant diabetes mellitus (PTDM) vary among reports from single-center observational studies and clinical trials. Using data from the United Renal Data System we identified 11 659 Medicare beneficiaries who received their first kidney transplant in 1996-2000. The cumulative incidence of PTDM was 9.1% (95% confidence interval = 8.6-9.7%), 16.0% (15.3-16.7%), and 24.0% (23.1-24.9%) at 3, 12, and 36 months post-transplant, respectively. Using Cox's proportional hazards analysis, risk factors for PTDM included age, African American race (relative risk = 1.68, range: 1.52-1.85, p < 0.0001), Hispanic ethnicity (1.35, range: 1.19-1.54, p < 0.0001), male donor (1.12, range: 1.03-1.21, p = 0.0090), increasing HLA mismatches, hepatitis C infection (1.33, range: 1.15-1.55, p < 0.0001), body mass index >or=30 kg/m2 (1.73, range: 1.57-1.90, p < 0.0001), and the use of tacrolimus as the initial maintenance immunosuppressive medication (1.53, range: 1.29-1.81, p < 0.0001). Factors that reduced the risk for PTDM included the use of mycophenolate mofetil, azathioprine, younger recipient age, glomerulonephritis as a cause of kidney failure, and a college education. As a time-dependent covariate in Cox analyses that also included multiple other risk factors, PTDM was associated with increased graft failure (1.63, 1.46-1.84, p < 0.0001), death-censored graft failure (1.46, 1.25-1.70, p < 0.0001), and mortality (1.87, 1.60-2.18, p < 0.0001). We conclude that high incidences of PTDM are associated with the type of initial maintenance immunosuppression, race, ethnicity, obesity and hepatitis C infection. It is a strong, independent predictor of graft failure and mortality. Efforts should be made to minimize the risk of this important complication.     

The Effect of Everolimus Versus Mycophenolate Upon Proteinuria Following Kidney Transplant and Relationship to Graft Outcomes

Although mTOR inhibitor use has been associated with proteinuria in kidney transplant recipients, dose dependency and impact on allograft function are unknown. In a post hoc analysis, we compared rates of proteinuria 3 months posttransplant among everolimus (EVR) and mycophenolate (MPA) treatment arms and used a time‐dependent model to correlate the risk of proteinuria to EVR trough levels up to 24 months posttransplant. eGFR and graft loss was compared by proteinuria status at 3 months. Of 833 randomized patients, 24%, 36% and 19% of lower exposure EVR (1.5 mg/day), higher exposure EVR (3.0 mg/day) and MPA‐treated patients had proteinuria ≥ 300 mg/g Cr at 3 months, respectively. EVR 1.5 was not associated with an increase in risk of proteinuria (HR 1.20; p = 0.19) unlike EVR 3.0 (HR 1.84; p < 0.001) versus MPA. EVR trough levels >8 ng/mL were significantly associated with proteinuria compared to 3–8 ng/mL (HR 1.86; p < 0.001). Those patients with proteinuria at 3 months and those who developed proteinuria thereafter had lower eGFR and higher graft loss at 24 months, regardless of treatment arm. We identify a dose‐dependent effect of EVR with the risk of proteinuria; however, its independent impact upon eGFR and graft survival at 2 years was not evident.     

Analysis of survival after liver transplantation in Galicia, Spain

BACKGROUND: Transplantation is the treatment of choice for many patients with end-stage liver disease. We evaluated the results of liver transplantation in Galicia, an autonomous community in Northwest Spain. METHODS: We analyzed 452 patients and 490 grafts from 1996 to 2000 for causes of loss with respect to recipient and donor variables using the actuarial method, Kaplan-Meier curves, log-rank test, and Cox proportional risks model. RESULTS: The overall graft survival was 77% and 64% at 1 and 5 years, respectively; while that of the patients was 83% and 69%. The risk factors for graft loss were donation in heart failure (HR = 4.91, CI:2.51-9.61); donor age (HR = 1.70, CI:1.01-2.85 between 40 and 60 years; HR = 2.37, CI:1.37-4.10 in those over 60 years, as compared to patients under 40); urgent transplant (HR = 3.95, CI:2.07-7.54); and transplant due to acute liver failure (HR = 3.53, CI:1.72-7.25) as compared to alcoholic cirrhosis. For patient death the risk factors were age of recipient over 60 years, compared to those under 40 (HR = 2.42, CI:1.11-5.28); foreign place of origin (HR = 2.02, CI:1.14-3.59); transplant due to viral cirrhosis (HR = 1.76, CI:1.03-3.02) and transplant due to acute liver failure (HR = 4.62, CI:2.12-10.06), as compared to alcoholic cirrhosis; urgent transplant (HR = 2.65, CI:1.48-4.72), and age of donor over 60 years, as compared to those under 40 (HR = 2.65, CI:1.48-4.72). Infections were the principal cause of death (45%), mostly in the first month (72%); while after the first year, 74% were due to recurrence of the primary disease and de novo malignancy. CONCLUSIONS: Graft and patient survivals were comparable to international registries. The donor characteristics had a greater influence on graft survival than on patient survival.     

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.     

Renal transplantation outcome and social deprivation in the French healthcare system: a cohort study using the European Deprivation Index

The study objective was to estimate the effect of social deprivation estimated by the European Deprivation Index (EDI) on the risk of death and graft failure on renal transplantation in France. EDI was calculated for 8701 of 9205 patients receiving a first renal transplantation between 2010 and 2014. Patients were separated in EDI quintiles of the general population. A Cox model (cs‐HR: cause‐specific hazard ratio of death or graft failure) and a Fine and Gray model (sd‐HR: subdistribution hazard ratio of death and graft failure) were used for the analysis. The 5th quintile group (most deprived) accounted for 32% of patients [2818 of 8701]. In the multivariate analysis, compared with quintile 1, the risk of death was higher for the 5^th quintile group in the complete cohort [cs‐HR: 1.31, 95% CI: (1.01–1.70), sd‐HR: 1.29, 95% CI: (1.00–1.68)], in the deceased donor group [cs‐HR: 1.31, 95% CI: (1.00–1.71), sd‐HR: 1.30, 95% CI: (1.00–1.70)] but not in living donor transplant patients. There was no association between the EDI groups and the risk of transplant failure. Social deprivation estimated by the EDI is associated with an increased risk of death in transplantation in France but not with the chance of allograft loss.     

Randomized Controlled Trial of Tacrolimus Versus Microemulsified Cyclosporin (TMC) in Liver Transplantation: Poststudy Surveillance to 3 Years

The 1-year results of the tacrolimus versus microemulsified cyclosporin (TMC) study found a benefit with tacrolimus immunosuppression after primary liver transplants in adults with respect to freedom from graft loss and immunological failure. The integrity of the randomization process was preserved for a further 2 years for poststudy surveillance. The data after 3 years confirms the significant difference between tacrolimus and cyclosporin with tacrolimus less likely to meet the composite primary endpoint (log rank p = 0.01; relative risk 0.75; 95% CI 0.60-0.95; p = 0.016). However, freedom from death or retransplantation no longer achieves statistical significance (relative risk 0.79; 95% CI 0.62-1.02; p = 0.065). A total of 62.1% of patients randomized to tacrolimus were alive at 3 years with their original graft and still on their allocated study medication, as compared with only 41.6% in the cyclosporin limb (p < 0.001). No difference was detected between tacrolimus and cyclosporin in hepatitis-C-positive patients with the available data. The TMC study confirms after 3 years of follow-up the benefits of tacrolimus-based immunosuppression over cyclosporin using C(0) monitoring.     

Impact of Immunosuppressive Medication on the Risk of Renal Allograft Failure due to Recurrent Glomerulonephritis

Recurrent glomerulonephritis is a major problem in kidney transplantation but the role of immunosuppression in preventing this complication is not known. We used data from the United States Renal Data System to examine the effect of immunosuppressive medication on allograft failure due to recurrent glomerulonephritis for 41 272 patients undergoing kidney transplantation from 1990 to 2003. Ten-year incidence of graft loss due to recurrent glomerulonephritis was 2.6% (95% confidence interval [CI]: 2.3–2.8%). After adjusting for important covariates, the use of cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, sirolimus or prednisone was not associated with graft failure due to recurrent glomerulonephritis. There was no difference between cyclosporine and tacrolimus or between azathioprine and mycophenolate mofetil in the risk of graft failure due to recurrent glomerulonephritis. However, any change in immunosuppression during follow-up was independently associated with graft loss due to recurrence (adjusted hazard ratio 1.30, 95% CI: 1.06–1.58, p = 0.01). In patients with a pretransplant diagnosis of glomerulonephritis, the risk of graft loss due to recurrence was not associated with any specific immunosuppressive medication. The selection of immunosuppression for kidney transplant recipients should not be made with the goal of reducing graft failure due to recurrent glomerulonephritis.