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Journal ArticleDOI

Improved Graft Survival after Renal Transplantation in the United States, 1988 to 1996

02 Mar 2000-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 342, Iss: 9, pp 605-612
TL;DR: There has been a substantial increase in short-term and long-term survival of kidney grafts from both living and cadaveric donors since 1988.
Abstract: Background The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known. Methods We analyzed the influence of demographic characteristics (age, sex, and race), transplant-related variables (living or cadaveric donor, panel-reactive antibody titer, extent of HLA matching, and cold-ischemia time), and post-transplantation variables (presence or absence of acute rejection, delayed graft function, and therapy with mycophenolate mofetil and tacrolimus) on graft survival for all 93,934 renal transplantations performed in the United States between 1988 and 1996. A regression analysis adjusted for these variables was used to estimate the risk of graft failure within the first year and more than one year after transplantation. Results From 1988 to 1996, the one-year survival rate for grafts from living donors increased from 88.8 to 93.9 percent, and the rate for cadaveric grafts increased...
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Journal ArticleDOI
TL;DR: This review considers the use of immunosuppressive drugs in organ transplantation, focusing on renal transplantation.
Abstract: Suppression of allograft rejection is central to successful organ transplantation; thus, immunosuppressive agents are crucial for successful allograft function. Immunosuppressive drugs are used for induction (intense immunosuppression in the initial days after transplantation), maintenance, and reversal of established rejection. This review considers the use of immunosuppressive drugs in organ transplantation, focusing on renal transplantation.

1,342 citations

Journal ArticleDOI
TL;DR: This work analyzed data provided by the Scientific Registry of Transplant Recipients regarding all adult first renal transplants between 1995 and 2000 to investigate how acute rejection rates have evolved on a national level in the U.S and how this has impacted graft survival in the most recent era of kidney transplantation.

1,157 citations

Journal ArticleDOI
TL;DR: A systematic review of studies comparing adult chronic dialysis patients with kidney transplantation recipients for clinical outcomes found significantly lower mortality associated with transplantation, and the relative magnitude of the benefit seemed to increase over time.

1,027 citations

Journal ArticleDOI
TL;DR: Current antirejection therapy, including calcineurin blockers such as cyclosporine and tacrolimus, the interleukin-2 signal-transduction inhibitor sirolimus and the purine-synthesis inhibitor mycophenolate mofetil are discussed, which inhibits the proliferation of T cells and B cells.
Abstract: This article provides a comprehensive, up-to-date review of methods to prevent early and late renal-allograft loss and to improve long-term outcomes in patients. The authors focus particular attention on the problem of late graft loss and discuss current antirejection therapy, including calcineurin blockers such as cyclosporine and tacrolimus, the interleukin-2 signal-transduction inhibitor sirolimus, and the purine-synthesis inhibitor mycophenolate mofetil, which inhibits the proliferation of T cells and B cells.

830 citations

Journal ArticleDOI
TL;DR: Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation, and one-year creatinine and Delta Creatinine values predict long-term renal graft survival.

683 citations


Cites methods from "Improved Graft Survival after Renal..."

  • ...A recent analysis of the UNOS/OPTN transplant database, confirmed that long-term renal graft survival measured as graft half-life has improved from 1988 to 199...

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References
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Book ChapterDOI
TL;DR: In this article, the product-limit (PL) estimator was proposed to estimate the proportion of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t).
Abstract: In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed. For random samples of size N the product-limit (PL) estimate can be defined as follows: L...

52,450 citations

Journal ArticleDOI
TL;DR: This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients.
Abstract: Mycophenolate mofetil (MMF), a new immunosuppressant that selectively inhibits proliferation of T and B lymphocytes, may reduce the frequency and severity of acute graft rejection. Acute graft rejection is the leading cause of graft loss in cadaveric renal transplantation. The purpose of this randomized, double-blind, multicenter study was to evaluate the efficacy and safety of MMF for the prevention of acute rejection episodes in adult patients during the first 6 months after renal transplantation. A total of 499 patients who were to receive a primary cadaveric renal allograft as their first transplant were randomized to receive MMF 1.0 g b.i.d. (MMF 2 g treatment group), MMF 1.5 g b.i.d. (MMF 3 g treatment group), or azathioprine 1-2 mg/kg/day. CsA, corticosteroids, and antithymocyte globulin (ATGAM®) were administered as part of a quadruple sequential induction protocol. The primary efficacy endpoint was biopsy-proven rejection or treatment failure (defined as graft loss, death, or premature withdrawal from the study for any reason) during the first 6 months after transplant. All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat. The 495 patients who received study drug were included in the safety and secondary efficacy analyses. Biopsy-proven acute rejection episodes or treatment failure occurred in 47.6% of patients in the azathioprine group compared with 31.1% (P=0.0015) and 31.3% (P=0.0021) of patients in the MMF 2 g and 3 g treatment groups, respectively. Time to first biopsy-proven rejection episode or treatment failure was significantly longer for MMF 2 g versus azathioprine (P=0.0036) and MMF 3 g versus azathioprine (P=0.0006). First biopsy-proven rejection alone occurred in 38.0% of patients who received azathioprine compared with 19.8% and 17.5% of patients who received MMF 2 g and 3 g, respectively. Patients in the azathioprine group received a greater number of full courses of antirejection treatment as compared with the MMF 2 g and MMF 3 g groups (44.5%, 24.8%, and 21.1%, respectively). The use of antilymphocyte agents to treat rejection was greater in the azathioprine group (20.1%) compared with the MMF 2 g group (10.3%) and the MMF 3 g group (5.4%). At 6 months after transplant, graft and patient survival were similar in all 3 treatment groups. The incidence and types of adverse events were similar among treatment groups, with the exception of a higher incidence of diarrhea, certain other infrequent gastrointestinal adverse events, clinically important leukopenia, and tissue-invasive CMV disease in the MMF groups, particularly in the MMF 3 g group. Three patients who received MMF developed lymphoma/lymphoproliferative disorder. This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients. This regimen also has an acceptable adverse event profile. The MMF 3 g dosage was considered to be somewhat less well tolerated than the MMF 2 g dosage.

1,278 citations

Journal ArticleDOI
TL;DR: Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations.
Abstract: Background. Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants. Methods. A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection. Results. One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. Conclusions. Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.

1,060 citations

Journal ArticleDOI
TL;DR: In this article, the authors found that acute rejection, CsA dosage < 5 mg/kg/day at 1 year, and infection are the major risk factors for the development of chronic rejection.
Abstract: Chronic rejection is a major barrier to long-term renal allograft survival. Cyclosporine, though effective at reducing graft loss to acute rejection, has had little impact on the incidence of chronic rejection. Between June 2, 1986 and January 22, 1991, 587 kidney-alone transplants (566 patients) were performed, and had been entered into our renal transplant database and had at least 1 year of follow-up: 103 with biopsy-proven chronic rejection (37 living-related donor, 66 cadaver) and 484 without chronic rejection (236 LRD 248 CAD). The 5-year patient survival was 84% for recipients with biopsy-proven chronic rejection vs. 89% without (P = .08). The 5-year graft survival was 31% for recipients with biopsy-proven chronic rejection vs. 81% without (P 50 years), gender, human leukocyte antigen matching, peak and transplant panel-reactive antibody, acute rejection episodes, infections (including cytomegalovirus, viral, and bacterial), donor age, and CsA dosage at 1 year ( or = 5 mg/kg). Logistic regression models were fit to the data using a forward stepwise selection procedure. In this analysis, risk factors included an acute rejection episode (P < .001), CsA dosage < 5 mg/kg/day at 1 year (P = .007), infection (P = .023), female gender (P = .042), and retransplant (P = .103). Individual analyses were done for CAD and LRD recipients. For both groups, important variables were acute rejection, infection, CsA dosage at 1 year, and age at transplant. In conclusion, acute rejection, CsA dosage < 5 mg/kg/day at 1 year, and infection are the major risk factors for the development of chronic rejection, suggesting that chronic rejection may be the result of inadequate immunosuppression (acute rejection episodes and low CsA dosage) or the production of inflammatory cytokines (infections).

662 citations

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