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Steven K Takemoto

Publications and source records attributed to Steven K Takemoto.

12 recordsLinked to original sources
PubMed2007

HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation.

The National Marrow Donor Program maintains a registry of volunteer donors for patients in need of a hematopoietic stem cell transplantation. Strategies for selecting a partially HLA-mismatched donor vary when a full match cannot be identified. Some transplantation centers limit the selection of mismatched donors to those sharing mismatched antigens within HLA-A and HLA-B cross-reactive groups (CREGs). To assess whether an HLA mismatch within a CREG group ("minor") may result in better outcome than a mismatch outside CREG groups ("major"), we analyzed validated outcomes data from 2709 bone marrow and peripheral blood stem cell transplantations. Three-hundred and ninety-six pairs (15%) were HLA-DRB1 allele matched but had an antigen-level mismatch at HLA-A or HLA-B. Univariate and multivariate analyses of engraftment, graft-versus-host disease, and survival showed that outcome is not significantly different between minor and major mismatches (P = .47, from the log-rank test for Kaplan-Meier survival). However, HLA-A, HLA-B, and HLA-DRB1 allele-matched cases had significantly better outcome than mismatched cases (P < .001). For patients without an HLA match, the selection of a CREG-compatible donor as tested does not improve outcome.

Alleles↗
PubMed2006

Outcomes of renal transplantation for recipients with lupus nephritis: analysis of the Organ Procurement and Transplantation Network database.

Prior analyses of transplant outcomes in lupus transplant recipients have not consisted of multivariate analyses in the modern immunosuppressive era. Here, we compared patient and graft outcomes in lupus and non-lupus recipients transplanted between 1996 to 2000 using the United Network of Organ Sharing/Organ Procurement Transplant Network database. We evaluated the impact of recipient and donor demographic factors, time on dialysis and the initial immunosuppression regimen on rejection rates and transplant outcomes. Univariate analysis showed similar graft but better patient survival rates for primary lupus and non-lupus transplant recipients (5-year patient survival rates for lupus cohort 85.2% for deceased donor transplants and 92.1% for living donor transplants as opposed to 82.1% and 89.8% respectively for the non-lupus cohort; P=0.05 and 0.03) but similar patient survival rates for deceased donor retransplant patients. After controlling for confounding factors, no differences in patient or graft survival were seen between the two groups. No difference in acute rejection rates were observed in deceased donor transplants, but there was a small but significant increase in the risk of acute rejection in living donor lupus transplant recipients (hazard ratio=1.19, P=0.05). Risk of graft failure was lower for deceased donor recipients receiving MMF (five-year graft loss rate=29.6% for MMF vs. 40.2% for those not receiving MMF, P<0.0001), but no differences were seen among living donor recipients. Outcomes were similar regardless of type of calcineurin inhibitor, induction therapy, and time on dialysis. We conclude that lupus transplant recipients have outcomes generally equivalent to non-lupus transplant recipients.

Adult↗
PubMed2006

Agreement of immunosuppression regimens described in Medicare pharmacy claims with the Organ Procurement and Transplantation Network survey.

The Organ Procurement and Transplantation Network (OPTN) collects intermittent survey data on immunosuppressive medication use that are studied frequently as research measures. Pharmacy billing claims may provide an accurate measure of immunosuppression use over time. Herein is characterized the agreement of Medicare pharmacy claims for immunosuppressive medications with OPTN reports. Data were drawn from the United States Renal Data System. Participants received a kidney transplant in 2000 to 2001 and had an OPTN record and a Medicare pharmacy claim for an immunosuppressive drug at transplant discharge and 6 mo and 1 yr after transplantation. The concordance (kappa) of the OPTN and claims (+/-30 d of survey) for indicated medication use was compared, and sensitivity, specificity, and predictive values for claims were computed, assuming OPTN as a "gold standard." Clinical trial participation and regimen changes were examined as explanations for discordance. A total of 4357 eligible subjects were identified. Concordance over observation ranged from excellent for calcineurin inhibitors (kappa > 0.86) to generally very good for adjunctive agents (kappa = 0.49 to 0.75) to poor for corticosteroids (kappa <0.15). Claims demonstrated high positive predictive values (> or =97%) but low negative predictive values (< or =13%) for OPTN-reported corticosteroid use. Regimen changes (28 to 75%) but not clinical trial participation (< or =21%) were identified frequently among cases with discordant indications of nonsteroid medication use. Close agreement of Medicare billing claims and the OPTN for indicated use of nonsteroid immunosuppressive medications supports both as useful measures of drug exposure. Low detection rates of OPTN-indicated corticosteroid use within claims require further examination.

Data Collection↗
PubMed2004

National conference to assess antibody-mediated rejection in solid organ transplantation.

The process of humoral rejection is multifaceted and has different manifestations in the various types of organ transplants. Because this process is emerging as a leading cause of graft loss, a conference was held in April 2003 to comprehensively address issues regarding humoral rejection. Though humoral rejection may result from different factors, discussion focused on a paradigm caused by antibodies, typically against donor HLA antigens, leading to the term 'antibody-mediated rejection' (AMR). Conference deliberations were separated into four workgroups: The Profiling Workgroup evaluated strengths and limitations of different methods for detecting HLA reactive antibody, and created risk assessment guidelines for AMR; The Diagnosis Workgroup reviewed clinical, pathologic, and serologic criteria for assessing AMR in renal, heart and lung transplant recipients; The Treatment Workgroup discussed advantages, limitations and possible mechanisms of action for desensitization protocols that may reverse AMR; and The Basic Science Workgroup presented animal and human immunologic models for humoral rejection and proposed potential targets for future intervention. This work represents a comprehensive review with contributions from experts in the fields of Transplantation Surgery, Medicine, Pathology, Histocompatibility, Immunology, and clinical trial design. Immunologic barriers once considered insurmountable are now consistently overcome to enable more patients to undergo organ transplantation.

Antibodies↗
PubMed2003

Graft survival following living-donor renal transplantation: a comparison of tacrolimus and cyclosporine microemulsion with mycophenolate mofetil and steroids.

BACKGROUND: Registry databases offer the statistical power to analyze differences in graft survival rates that may not be detected in randomized clinical trials. This study analyses 2-year graft survival using tacrolimus (tac) or cyclosporine (CsA) with mycophenolate mofetil (MMF) and steroids. METHODS: Data reported to the United Network for Organ Sharing Renal Transplant Registry for living-donor kidney patients receiving a transplant during 1998 to 1999 were included. The primary end point was graft survival after adjustment for confounding variables. A Cox model multivariate analysis was used to adjust for potential confounding factors. RESULTS: Patients receiving CsA-MMF (n=4,686) and tac-MMF (n=2,393) were included. Unadjusted all-cause 2-year graft survival rate was significantly higher with CsA-MMF than tac-MMF (94.3% vs. 92.2%, P=0.0006). After adjustment for potential confounding factors, risk of graft failure at 2 years was significantly higher in patients receiving tac-MMF versus CsA-MMF for both all-cause graft failure (hazards ratio [HR] 1.28, 95% confidence interval [CI] 1.09-1.49, P=0.002) and death-censored graft failure (HR 1.25, 95% CI 1.05-1.49, P=0.013). Other independent risk factors for graft failure were recipient or donor age greater than 55 years, female sex, pretransplant blood transfusions, one or two haplotype mismatches compared with zero haplotype mismatch, and panel reactive antibody (PRA) greater than 30%. CONCLUSIONS: Our findings demonstrate that 2-year renal allograft survival is significantly higher in living-donor recipients receiving CsA compared with tac as initial immunosuppression in combination with MMF.

Adolescent↗
PubMed2003

Report of the American Society of Transplantation conference on immunosuppressive drugs and the use of generic immunosuppressants.

Considerable economic and health-related costs are associated with the life-long maintenance immunosuppressive therapy required to prevent transplant rejection. Generic medications have the potential of providing equivalent therapeutic efficacy at a lower economic cost. In 2001, the American Society of Transplantation invited experts to review the data and issues associated with the approval and use of generic immunosuppressants. A summary of that meeting is reported here. The generic medication approval process has been in effect for more than 30 years. All marketed generic cyclosporin formulations have met FDA criteria demonstrating bioequivalence in healthy subjects, and some were also tested in transplant recipients. Most participants agreed that generic narrow therapeutic index immunosuppressive agents provide adequate de novo immunosuppression in low-risk transplant recipients. However, some participants expressed concern regarding the currently unquantified risk that may be associated with switching immunosuppressive agents under uncontrolled circumstances. There was broad agreement among the participants that generic medications should be clearly labeled and distinguishable from innovator drugs, and that patients should be educated to inform their physicians of any switch to or among generic alternatives. There was also strong support in favor of requiring studies to demonstrate bioequivalence in potentially at-risk patient populations, specifically African-Americans and pediatric patients.

Cyclosporine↗
PubMed2003

HLA matching in the new millennium.

Despite increasing graft survival rates associated with advances in immunosuppression, the relative risk of graft loss for transplants with HLA mismatches has remained at about 25% higher than those with 0 ABDR-mismatches. The percentage of 0 DR-mismatched transplants peaked at 25% in 1994 and has decreased yearly to 15% in 2003. The percentage of transplants with a flow crossmatch increased from 5% in 1988 to 38% in 2003. Prior to 1995, a flow crossmatch was associated with a decreased risk of graft loss. Antigen distributions of HLA-A, -B, -DR and CREGs are summarized and reveal many differences between Whites and Blacks. HLA matching models with 9, 18 and 36 CREGs are presented. The more complex models yielded fewer cases but outcomes approached that achieved for 0 ABDR-mismatched transplanted.

Blood Group Incompatibility↗
PubMed2003

Multivariate analyses of antibody induction therapies.

1. Between 1997-2002 a 3-fold increase in induction therapy was attributed to surging use of Simulect, Zenapax and Thymoglobulin. 2. Induction therapy reduced the hazard ratio by 8% in deceased and 13% in living donor transplants and reduced the risk of rejection by 26% in deceased and 13% in living donor allografts. 3. Thymoglobulin was used more often in sensitized and retransplanted recipients and those with delayed graft function. Zenapax was used more often in pediatric recipients and those receiving MMF. Simulect was used more often in recipients not receiving MMF. 4. Simulect was associated with increased risk of rejection, perhaps due to a negative association with MMF maintenance immunosuppression. On the other hand, recipients not given MMF had a decreased hazard ratio with Simulect induction. 5. Induction reduced the risk of rejection in deceased donor allografts with delayed graft function, and sensitized and Black recipients. However a resultant impact on hazard ratio was not observed in these high-risk cohorts. 6. When considering HLA compatibility, induction reduced the hazard ratio only for DR-mismatched deceased donor allografts. Thymoglobulin induction increased the hazard ratio for zero-haplotype-mismatched living donor transplants.

Graft Rejection↗
PubMed2002

All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies.

BACKGROUND: Recent studies show that almost all patients who have rejected a kidney transplant had human leukocyte antigen (HLA) antibodies. In this study, we sought to determine whether patients develop HLA antibodies before chronic rejection. METHODS: For the past 8 years, 139 patients who had undergone kidney transplantation were systematically examined, using an enzyme-linked immunosorbent assay-based method, for the development of class-I and class-II HLA antibodies 3 months, 6 months, and yearly after transplantation. Chronic rejection was diagnosed by biopsy. RESULTS: Among 29 patients with chronic rejection, 100% of the patients had HLA antibodies before rejection. Of these patients, 14 patients developed antibodies de novo. In contrast, among 110 patients with stable function, 27% of the patients developed HLA antibodies posttransplant (P<0.001). CONCLUSIONS: HLA antibodies were found in 29 consecutive cases of chronic rejection failures as much as one year before the loss of grafts. We conclude that HLA antibodies may be a prerequisite for chronic immunologic rejection.

Autoantibodies↗
PubMed2002

Patterns of administration of antibody induction therapy and their associated outcomes.

1. There was a dramatic shift in the type of induction therapy used between 1996-2000. In 2000, more than half of recipients received induction therapy. 2. The type of transplants strongly influenced the use of antibody induction. LD recipients were least likely to receive antibody induction followed by unsensitized, sensitized cadaveric and SPK recipients. 3. Pan-T antibody induction was used more frequently in patients with DGF and in high immunologic risk groups. 4. IL-2 receptor antagonists have become the dominant induction therapy; even for recipients with high immunologic risk or those with DGF. 5. We cannot demonstrate the effects of pan-T antibody induction on the resolution of DGF. Pan-T antibody induction did not improve graft survival in any cohorts, although it was associated with lower acute rejection rates in LD and unsensitized groups. 6. IL-2R antibody induction therapy was associated with lower acute rejection and graft failure at one year in LD and unsensitized groups. However, this trend cannot be demonstrated in higher immunologic risk groups ie., sensitized cadaveric and SPK.

Adolescent↗