Jonathan A. Morris

Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration.

Background. To evaluate the association of long-term continuous mycophenolate mofetil (MMF) versus azathioprine (AZA) therapy and renal allograft function, as measured by the slope of reciprocal creatinine, we analyzed 49,666 primary renal allograft recipients reported to the United States Renal Data System between October 31, 1988 and June 30, 1998. Methods. The primary study endpoint was defined as a greater than 20% decrease below a 6-month baseline of 1/serum creatinine (SCr) (slope of reciprocal creatinine) at or beyond 1 year after transplantation. A secondary endpoint was defined as reaching an SCr value greater than 1.6 mg/dL. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to investigate the risk of reaching the study endpoints. Multivariate analyses were corrected for potential confounding covariates. Results. According to the Cox proportional hazard model, 12-month continued therapy of MMF versus AZA was associated with a protective effect against declining renal function, as measured by the slope of reciprocal creatinine (relative risk [RR]=0.84, confidence interval 0.78–0.91, P <0.001). For 24-month continued therapy of MMF versus AZA, MMF was associated with a further decreased risk for a decline in renal function (RR=0.66, confidence interval=0.57–0.77, P <0.001). Furthermore, MMF was associated with a protective effect against reaching the SCr threshold of 1.6 mg/dL (RR=0.80, P <0.001) beyond 12 months posttransplantation. Conclusions. Continuous use of MMF versus AZA was associated with a protective effect against declining renal function beyond 1 year after transplantation. Further study is needed to confirm that continued MMF therapy is protective against long-term deterioration in renal function.

Long-Term Use of Mycophenolate Mofetil is Associated With a Reduction in the Incidence and Risk of Late Rejection

To evaluate the association of long‐term continuous (minimum 1 year) mycophenolate mofetil (MMF) vs. azathioprine (AZA) therapy with the incidence of late acute rejection, we analyzed 47 693 primary renal allograft recipients reported to the United States Renal Data System between 1988 and 1998.

Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with decreased renal allograft survival.

To evaluate the association between a regimen of cyclosporine microemulsion (CsA) + sirolimus (Rapa) treatment versus CsA and mycophenolate mofetil (MMF) and renal allograft survival, we analyzed 23 016 primary recipients reported to the Scientific Registry of Transplant Recipients between January 1, 1998 and July 26, 2003.

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

Abstract:  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.

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

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

Snydman DR, Kistler KD, Ulsh P, Bergman GE, Vensak J, Morris J. 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.
Clin Transplant 2011: 25: E455–E462.

Real-World Doxercalciferol Treatment in SHPT CKD Stage 3 and 4: An Analysis of Change in iPTH and Accordance to KDOQI Recommendations

Background: National Kidney Foundation’s Kidney Disease Outcome Quality Initiative (KDOQI) guidelines offer an outline for providing standardized care for best outcomes in chronic kidney disease (CKD). It is unknown whether real-world treatment practices follow these guidelines. Methods: The Hectorol® Registry Outcome in Chronic Kidney Disease (HeROICkd™), an observational patient registry, captured information on adult patients with CKD Stage 3 or 4 throughout US clinics during a 9-month observation period. Data were collected quarterly from patients’ medical records, throughout each patient’s normal treatment course. The proportion of patients with intact parathyroid hormone (iPTH) levels within KDOQI guidelines, change in iPTH, Ca, P, and Ca × P product over the 9-month observation period, incidence of hypercalcemia and hyperphosphatemia, and predictors of change in iPTH were examined. Results: 1,339 CKD Stage 3 and 4 patients from 78 nephrology and internal medicine clinics were included. 40% of CKD Stage 3 participants and 45% of Stage 4 had a 30% or greater reduction in iPTH levels from baseline to 9 months follow-up. While the proportion of CKD Stage 3 and 4 participants with iPTH levels within the KDOQI recommendations improved significantly over the 9 months, it was still modest, at 28% and 23%, respectively. Mean doxercalciferol dose was below that recommended in the package insert and a minority of patients had all mineral metabolism parameters (iPTH, Ca, P) regularly recorded in their medical records. Conclusions: The results of this registry, which examined iPTH treatment with doxercalciferol in CKD Stage 3 and 4, suggest that in the real-world treatment setting, the adherence to KDOQI guidelines is not optimal.

THE ASSOCIATION BETWEEN CYTOMEGALOVIRUS IMMUNE GLOBULIN (CMVIG) USE AND LONG-TERM RECIPIENT AND GRAFT SURVIVAL IN PEDIATRIC HEART TRANSPLANTATION RECIPIENTS: 543

D.R. Snydman1, K. Kistler2, J. Morris3, P. Ulsh4 1Division Of Geographic Medicine And Infectious Diseases And Hospital Epidemiologist, Tufts Medical Center, Tufts University School of Medicine, Boston/UNITED STATES OF AMERICA, 2Clin. Ops & Health Outcomes, ProSanos Corp., Harrisburg/UNITED STATES OF AMERICA, 3, ProSanos Corporation, Harrisburg/PA/UNITED STATES OF AMERICA, 4, CSL Behring, King of Prussia/UNITED STATES OF AMERICA