Calcineurin inhibitor avoidance versus steroid avoidance following kidney transplantation: Postoperative complications.

This study compared early postoperative complications in kidney transplant recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free regimen or a tacrolimus-based steroid-free regimen. We used a single-center, prospective, sequential but nonrandomized study design. Consecutive recipients of primary cadaveric or non-HLA identical kidney transplant recipients received either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning postoperative day 3, mycophenolate mofetil 1 gm twice a day, and methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome measures were patient and graft survival, BPAR, surgical and wound complications, viral infections and posttransplant diabetes mellitus (PTDM). Both groups had excellent early outcomes with no significant difference in patient or graft survival, early renal function, BPAR, surgical or wound complications, or viral infections between the two groups. Patients in the sirolimus-based CNI-free group had a significantly higher incidence of PTDM and a trend toward more discontinuation due to drug toxicity. Whether either regimen improves long-term outcomes awaits longer follow-up.

Short-term results under three different immunosuppressive regimens at one center.

We examined short-term outcomes and posttransplant medical complications under three different immunosuppressive regimens at a single center. The study design was a randomized, prospective, open-label trial comparing a calcineurin inhibitor-free (CNI) protocol to standard triple therapy with tacrolimus, prednisone, and mycophenolate mofetil. They were also compared to a concurrent but nonrandomized third cohort treated with a prednisone-free protocol. All three groups had excellent early outcomes with no significant difference in patient or graft survival or biopsy-proven acute rejection. Serum creatinine was significantly lower in the CNI-free recipients. Lipid panels and posttransplant diabetes mellitus were significantly lower in the prednisone-free patients. Prednisone-free kidney transplant recipients have improved early glucose metabolism and hyperlipidemia compared to CNI-free or standard triple therapy recipients with comparable rejection and graft survival rates.

Kidney transplantation in a veterans administration medical center: 40 years' experience.

OBJECTIVES: Advances in immunosuppressive therapy have led to substantial improvements in kidney transplant outcomes in the past 20 years. Kidney transplantation activity started in 1963 at the Veterans Administration Medical Center in Nashville, Tennessee, and continues to grow with increasing numbers of transplants from living-related and unrelated donors. In this study, patient and graft survival rates during 2 different periods were evaluated and compared with non-veterans-administration centers. MATERIALS AND METHODS: Six hundred fourteen kidney transplants were performed between March 1963 and December 2002. For analytic purposes, the 40-year experience was divided into 2 eras based on the immunosuppressive agents used. Azathioprine and prednisone were the immunosuppressive agents used in era 1. A calcineurin-inhibitor-based triple immunosuppressive regimen initially including azathioprine and prednisone and later, mycophenolate mofetil and prednisone, was the preferred immunosuppressive regimen in era 2. RESULTS: In era 1, 1-year patient and graft survival rates were 72.5% and 50%, and 89% and 75% for deceased-donor and living-donor transplants respectively. In era 2, patient survival rates increased to 95.1% and 87.8% for 1 and 3 years respectively, while graft survival increased to 87.6% and 74.9%. Forty-three percent of deceased-donor and 21% of living-donor kidneys were lost owing to rejection in era 1. In era 2, the incidence of acute rejection was 14.5% overall. CONCLUSIONS: Overall, our results are comparable with non-veterans-administration centers and the national average and show that kidney transplantation offers veteran patients with end-stage renal disease a safe and effective treatment with increased quality of life.

Life satisfaction in renal transplant recipients: preliminary results from the transplant learning center.

The Transplant Learning Center (TLC) was designed to improve quality of life (QOL) and preserve graft function in solid-organ transplant recipients. To meet the specific goals of the program, the Life Satisfaction Index and Transplant Care Index were designed to serve as composite measures for measuring transplant-specific QOL and the ability to care for a transplant, respectively. In this study, we analyzed self-reported health information to examine relationships between comorbidities and individual posttransplantation side effects, life satisfaction, and transplant care, defined by renal transplant recipients. Patients entered the TLC through self-referral or referral by a health professional. Included in the analysis were 3,676 TLC enrollees with a mean time since transplantation of 4.8 years. Comorbidities and adverse effects were common, with high blood pressure reported by 89% of respondents and unusual hair growth reported by 70%. Sexual dysfunction and headache had a greater impact on QOL than more common adverse effects, such as changes in body and facial shape, hirsutism, and tremor. Regression modeling was used to identify the most significant associations between QOL indices and structural (nonmedical), medical, and psychosocial factors. Greater life satisfaction was most strongly associated with being in control of one's health and living a normally active life with satisfying emotional relationships. Management of such clinical problems as adverse effects of medication and nonadherence should be informed by the patient's perspective. Clinicians should actively solicit information about physical activity, appearance concerns, side effects of medications, nonadherence, and sexual and relationship issues when evaluating renal transplant recipients.

Renal transplantation.

Renal Transplantation has progressed from an experiment in surgery, nephrology, and immunology to the preferred means of renal replacement therapy for patients with end-stage renal disease. Patient and graft survival rates are spectacular in the short run and improving steadily in the long. The current state of the art reflects deepened understanding of the alloimmune response and the T lymphocyte activation cascade in part driving the discovery of ever more potent immunosuppressive agents. Important issues remain such as chronic allograft dysfunction, the organ shortage, and tolerance induction. In this review, we will look at the history, the expanding treatment options based on better understanding of the immunobiology of alloantigen response, and the persistent challenges awaiting.

Prophylaxis and treatment of gastrointestinal complications following transplantation.

Most transplant recipients will experience some type of gastrointestinal (GI) complication. These effects often are caused by infectious damage induced by a variety of opportunistic organisms, but they also may be due to mechanical injury during surgery or to metabolic or organ toxicity associated with immunosuppressive regimens. Although some of these GI complications can substantially impair quality of life or even carry significant mortality risk, many of them can be prevented, and most of them can be treated medically without the need to stop immunosuppression and expose the patient to the risk of rejection. Limiting the use of steroids, giving prophylactic antiviral and antifungal agents (particularly to patients at risk) and adopting a low threshold for endoscopy are among the most important measures that can be used to avoid GI complications after transplantation.

Transplantation for the millennium: attaining tolerance in our time--the Holy Grail.

Despite tremendous advances in organ transplantation over the past 40 years, life-long immunosuppression is still required to maintain the transplanted organ. The induction of human tolerance to defined foreign antigens while maintaining completely intact all the rest of the immune repertoire, in the absence of maintenance immunosuppression, continues to be the dream of the transplant scientist and clinician, the "Holy Grail," the quest which energizes much recent research. This article presents an overview on recent developments on transplantation tolerance.

Drug substitution in transplantation: a National Kidney Foundation White Paper.

Specific safeguards to guide the approval process and substitution practices for generic immunosuppressive agents are necessary for the effective delivery of patient care. Currently, the Food and Drug Administration (FDA) requires the demonstration of bioequivalence of generic drugs to innovator drugs in normal healthy subjects, a criterion that may be insufficient for critical-dose drugs. For generic equivalents of critical-dose drugs and for innovator critical-dose drugs, there should be a requirement for replicate studies measuring intrasubject variability and subject-treatment interactions to establish that bioequivalence holds true. Extensive testing of generic drugs in all target patient types is impractical and should not be required. However, when evidence suggests that the bioavailability of a critical-dose drug may vary substantially in certain subgroups, the FDA should require a demonstration of bioequivalence of generic versions to innovator products in these representative target populations. Changes in the approval process for generics should be accompanied by more consistent substitution practices. Pharmacists should notify the prescribing physician and patient whenever a critical-dose drug (generic or brand name) is dispensed in a different formulation from the one the patient has been taking. Therapeutic substitution for such drugs should not be made unless the prescribing physician has granted approval. The health care provider should consider instituting appropriate monitoring whenever patients are switched between generic formulations or between innovator drugs and generic formulations. Patients should be well informed about generic substitutes so that they can participate in treatment choices.