RESUMEN
Preemptive kidney transplant (PKTx) and kidney transplant (KTx) within 1 year of dialysis initiation have been associated with superior outcomes. Wait times should be minimal for transplants with living donors; however, there is lack of literature studying utilization of timely KTx in this population. We designed this retrospective study using data from United Network for Organ Sharing Standard Transplant Analysis and Research files from 2000 to 2012 to assess the trends in utilization of PKTx and Early KTx (combination of PKTx or transplant within 1 year of dialysis initiation) in recipients of living donor KTx. Only 32.6% transplants were PKTx, and 61.9% were Early KTx. A significant improvement in proportion of PKTx was seen from 27.5% in 2000 to 35.4% in 2006, with no change since. Similarly, the proportion of Early KTx increased from 61.4% in 2000 to 63.6% in 2006, with no increase since. Similar results were seen after adjusted analysis and were independent of living donor type. Although there was some improvement in utilization of timely transplants in the early part of the last decade, there has been no improvement since. Considering the benefits of timely kidney transplant, it is important to understand the reasons behind the same and to improve utilization.
Asunto(s)
Fallo Renal Crónico/cirugía , Trasplante de Riñón , Donadores Vivos , Diálisis Renal , Obtención de Tejidos y Órganos/estadística & datos numéricos , Obtención de Tejidos y Órganos/normas , Adulto , Anciano , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
In this Phase 2b study, 331 low-to-moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of tofacitinib (CP-690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy-proven acute rejection (BPAR) with a serum creatinine increase of ≥0.3 mg/dL and ≥20% (clinical BPAR) at Month 6 and measured GFR at Month 12. Similar 6-month incidences of clinical BPAR (11%, 7% and 9%) were observed for MI, LI and CsA. Measured GFRs were higher (p < 0.01) at Month 12 for MI and LI versus CsA (65 mL/min, 65 mL/min vs. 54 mL/min). Fewer (p < 0.05) patients in MI or LI developed chronic allograft nephropathy at Month 12 compared with CsA (25%, 24% vs. 48%). Serious infections developed in 45%, 37% and 25% of patients in MI, LI and CsA, respectively. Anemia, neutropenia and posttransplant lymphoproliferative disorder occurred more frequently in MI and LI compared with CsA. Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side-effects at the doses evaluated.
Asunto(s)
Inmunosupresores/uso terapéutico , Janus Quinasa 3/antagonistas & inhibidores , Trasplante de Riñón , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Adulto , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Masculino , Persona de Mediana Edad , Piperidinas , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , Pirroles/efectos adversos , Pirroles/farmacocinéticaRESUMEN
Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1:2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (± standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 ± 22.3 vs. 49.5 ± 17.7 mL/min/1.73 m(2) , p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.
Asunto(s)
Trasplante de Riñón/fisiología , Proteína Quinasa C/antagonistas & inhibidores , Pirroles/uso terapéutico , Quinazolinas/uso terapéutico , Adulto , Inhibidores de la Calcineurina , Femenino , Humanos , Masculino , Ácido Micofenólico/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
Racial differences on the outcome of simultaneous pancreas and kidney (SPK) transplantation have not been well studied. We compared mortality and graft survival of African Americans (AA) recipients to other racial/ethnic groups (non-AA) using the national data. We studied a total of 6585 adult SPK transplants performed in the United States between January 1, 2000 and December 31, 2007. We performed multivariate logistic regression analyses to determine risk factors associated with early graft failure and immune-mediated late graft loss. We used conditional Kaplan-Meier survival and multivariate Cox regression analyses to estimate late death-censored kidney and pancreas graft failure and death between the groups. Although there was no racial disparity in the first 90 days, AA patients had 38% and 47% higher risk for late death-censored kidney and pancreas graft failure, respectively (p = 0.006 and 0.001). AA patients were twice more likely to lose the kidney and pancreas graft due to rejection (OR 2.31 and 1.86, p = 0.002 and 0.008, respectively). Bladder pancreas drainage was associated with inferior patient survival (HR 1.42, 95% CI 1.15, 1.75, p = 0.001). In the era of modern immunosuppression, AA SPK transplant patients continue to have inferior graft outcome. Additional studies to explore the mechanisms of such racial disparity are warranted.
Asunto(s)
Negro o Afroamericano , Supervivencia de Injerto , Trasplante de Riñón/etnología , Trasplante de Riñón/mortalidad , Trasplante de Páncreas/etnología , Trasplante de Páncreas/mortalidad , Adulto , Femenino , Rechazo de Injerto/etnología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3-8 and 6-12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab +/- corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m(2) in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: -1.7, 6.4 and -5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA.
Asunto(s)
Trasplante de Riñón/métodos , Ácido Micofenólico/administración & dosificación , Corticoesteroides , Adulto , Anticuerpos Monoclonales , Basiliximab , Biopsia , Inhibidores Enzimáticos , Everolimus , Femenino , Humanos , Inmunosupresores/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Proteínas Recombinantes de Fusión , Seguridad , Sirolimus/efectos adversos , Sirolimus/análogos & derivados , Resultado del TratamientoRESUMEN
Mycophenolate mofetil (MMF) was developed with cyclosporine as a fixed-dose immunosuppressant. More recent data indicate a relationship between mycophenolic acid (MPA) exposure in individuals and clinical endpoints of rejection and toxicity. This 2-year, open-label, randomized, multicenter trial compared the efficacy and safety of concentration-controlled MMF (MMF(CC)) dosing with a fixed-dose regimen in 720 kidney recipients. Patients received either (A) MMF(CC) and reduced-level calcineurin inhibitor (MMF(CC)/CNI(RL)); (B) MMF(CC) and standard-level CNI (MMF(CC)/CNI(SL)); or (C) fixed-dose MMF and CNI(SL) (MMF(FD)/CNI(SL)). Antibody induction and steroid use were according to center practice. The primary endpoint was noninferiority (alpha= 0.05) of group A versus group C for treatment failure (including biopsy-proven acute rejection [BPAR], graft loss and death) at 1 year. Although mean CNI trough levels in group A did not reach the prespecified targets, they were statistically lower than those in groups B and C (p < or = 0.01 for each comparison). BPAR rates (8.5%) were low across groups. Group A had 19% fewer treatment failures (23% vs. 28%, p = 0.18). MMF doses were highest (p < 0.05), with withdrawals for adverse events the fewest (p = 0.02), in group A. Of the 80% of subjects taking tacrolimus (Tac), those with higher MPA exposure had significantly less rejection (p < 0.001) and diarrhea correlated with Tac, but not with MPA levels. Thus, MMF(CC) with low-dose CNI resulted in outcomes not inferior to those with standard CNI exposure and MMF(FD), indicating potential utility of MMF(CC) in CNI-sparing regimens.
Asunto(s)
Inhibidores de la Calcineurina , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Adulto , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Trasplante de Riñón/inmunología , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/farmacocinética , Estudios Prospectivos , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Resultado del TratamientoRESUMEN
New onset diabetes after transplantation (NODAT) and impaired fasting glucose (IFG) are common in kidney transplant recipients (KTRs). Calcinuerin inhibitor (CNI) therapy is a causal risk factor. NODAT is associated with increased mortality and diminished graft survival. We studied the incidence of NODAT and IFG in KTRs before and after a medically indicated switch of CNI therapy from cyclosporine (CsA) to tacrolimus (Tac). The study population consisted of 704 nondiabetic KTRs. Of them, 171 underwent conversion from CsA to Tac (group I) and 533 remained on the CsA since transplantation (Group II). Time-dependent Cox regression and generalized estimating equations were used to account for sequential CNI exposure. NODAT and IFG occurred in 15.2% and 22.1% of group I subjects and 15.6% and 25.8% of group II subjects, respectively (p = 0.90 for NODAT and p = 0.38 for IFG). Accounting for equal follow-up time since conversion from CsA to Tac, the adjusted 5-year NODAT-free survival was 87.4% and 91.4% in group I and group II, respectively (p = 0.90). In conclusion, conversion to Tac, compared to continuous exposure to CsA, carries quantitatively similar risk of impaired glucose metabolism in KTRs in the late posttransplant period.
Asunto(s)
Ciclosporina/inmunología , Glucosa/metabolismo , Inmunosupresores/inmunología , Trasplante de Riñón/inmunología , Tacrolimus/inmunología , Glucemia/análisis , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Ayuno , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Guías como Asunto , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Cytomegalovirus (CMV) disease is relatively common following solid organ transplant, particularly if a serologically negative recipient receives an organ from a serologically positive donor (D+/R-). Although valganciclovir is approved for the treatment of CMV retinitis in AIDS patients and is used for the prophylaxis against CMV infection in solid organ transplant patients, the current standard treatment for CMV disease in solid organ transplant recipients remains intravenous ganciclovir. We retrospectively reviewed our experience using valganciclovir as treatment for CMV disease in CMV D+/R- kidney and/or pancreas transplant recipients from March 2002 to June 2005. A total of 37 cases with primary CMV disease were diagnosed and treated with either intravenous ganciclovir as induction followed with valganciclovir or valganciclovir from the beginning. We compared clinical outcomes and viremia between the two groups. Our data suggest that valganciclovir is an effective treatment modality for primary CMV disease in kidney and/or pancreas transplant recipients. It led to the resolution of disease and undetectable viremia. Valganciclovir allowed for early initiation of treatment and for treatment to be given as an outpatient. These advantages of valganciclovir have both health and economic impact for patients with CMV disease.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/análogos & derivados , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias/virología , Adulto , Infecciones por Citomegalovirus/epidemiología , ADN Viral/aislamiento & purificación , ADN Viral/orina , Quimioterapia Combinada , Femenino , Ganciclovir/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/epidemiología , Uremia/virología , ValganciclovirRESUMEN
INTRODUCTION: Fabry's disease is an X-linked error of glycosphingolipid metabolism. Clinical manifestations of the disease are secondary to accumulation of glycosphingolipids in various tissues. Renal failure and vascular complications are common. There are conflicting reports regarding the outcomes of patients with Fabry's disease after renal transplantation. METHODS: We reviewed the United States Renal Data System Registry database from 1988 and 1998, and found 93 patients with Fabry's disease who had received a renal transplant. Case-matched patients were identified to serve as controls. RESULTS: Patients with Fabry's disease demonstrated equivalent 5-year patient and graft survival, compared with controls (83% and 75%, respectively, for those with Fabry's disease vs. 82% and 67% for controls). CONCLUSION: Despite their high risk for cardiovascular complications, patients with Fabry's disease have excellent outcomes after renal transplantation.
Asunto(s)
Enfermedad de Fabry/cirugía , Trasplante de Riñón , Adulto , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Riñón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Sistema de Registros , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an analysis of the United States Renal Transplant Data Registry (USRDS). METHODS: All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. RESULTS: A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P<0.001). For both AZA and MMF three-year graft survival improved with fewer HLA donor-recipient mismatches. Comparing zero antigen mismatches to six antigen mismatches, the relative improvement was comparable for both patients on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard model the relative risk for graft loss decreased significantly in both the AZA and MMF treated patients with increased HLA matching. CONCLUSION: The use of MMF does not obviate the benefits of HLA matching, while HLA matching does not minimize the benefits of MMF on long term graft survival. Our study would suggest that HLA matching and MMF therapy are additive factors in decreasing the risk for renal allograft loss.
Asunto(s)
Antígenos HLA-A/farmacología , Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacología , Azatioprina/uso terapéutico , Estudios de Cohortes , Interacciones Farmacológicas , Femenino , Supervivencia de Injerto/efectos de los fármacos , Antígenos HLA-A/inmunología , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
BACKGROUND: Despite the known differences in immunological reactivity between males and females, no differences in graft survival have been described among renal transplant recipients with regard to gender. To address this paradox, we analyzed data from 73,477 primary renal transplants collected in the US Renal Data System database. METHODS: Logistic regression and Cox proportional hazard models were used to investigate the primary study end points, graft loss secondary to acute rejection (AR) or chronic allograft failure (CAF). CAF was defined as graft loss beyond 6 months, not attributable to death, recurrent disease, acute rejection, thrombosis, infection, noncompliance, or technical problems. The models adjusted for 15 covariates including immunosuppressive regimen, and donor and recipient characteristics. RESULTS: The overall 8-year graft and patient survivals were significantly better in female renal transplant recipients compared with male recipients. However graft survival censored for death was not significantly different by gender. By multivariate analysis, females had a 10% increased odds of AR (OR=1.10, CI 1.02-1.12), but conversely a 10% lower risk of graft loss secondary to CAF (RR=0.9, CI 0.85-0.96). The risk for CAF increased significantly with increasing age for both males and females, but this effect was greater for males than for females (P<0.001). CONCLUSION: Although female renal transplant recipients have a similar death censored graft survival compared with males, there are important differences in immunological behavior. Females have a higher risk of AR while having a decreased risk of graft loss secondary to CAF.
Asunto(s)
Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Enfermedad Crónica , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores Sexuales , Trasplante Homólogo/inmunologíaRESUMEN
BACKGROUND: Acute rejection (AR) remains a major risk factor for the development of chronic renal allograft failure (CAF), which is a major cause of late graft loss. With the introduction of several newer immunosuppressive agents (e.g., mycophenolate mofetil, tacrolimus and neoral) acute rejection rates have been steadily decreasing. However, the incidence of CAF has not decreased as dramatically as the incidence of acute rejection. One possible explanation is that the impact of AR on CAF is changing. The goal of this study was to analyze the relative impact of AR era on the development of CAF. METHODS: We evaluated 63,045 primary renal transplant recipients reported to the USRDS from 1988 to 1997. CAF was defined as graft loss after 6 months posttransplantation, censored for death, acute rejection, thrombosis, infection, surgical complications, or recurrent disease. A Cox proportional hazard model correcting for 15 possible confounding factors evaluated the relative impact of AR on CAF. The era effect (years 1988-1989, 1990-1991, 1992-1993, 1994-1995 and 1996-1997) was evaluated by an era versus AR interaction term. RESULTS: An AR episode within the first 6 months after transplantation was the most important risk factor for subsequent CAF (RR=2.4, CI 2.3-2.5). Compared with the reference group (1988-89 with no rejection), having an AR episode in 1988-89, 1990-1991, 1992-1993, 1994-1995, and 1996-1997, conferred a 1.67, 2.35, 3.4, 4.98 and 5.2-fold relative risk for the subsequent development of CAF (P<0.001). CONCLUSIONS: Independently of known confounding variables, the impact of AR on CAF has significantly increased from 1988 to 1997. This effect may in part explain the relative lack of improvements in long term renal allograft survival, despite a decline in AR rates.
Asunto(s)
Rechazo de Injerto/fisiopatología , Trasplante de Riñón/inmunología , Enfermedad Aguda , Adulto , Femenino , Supervivencia de Injerto/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Trasplante Homólogo/inmunologíaRESUMEN
BACKGROUND: The elderly are the fastest growing segment of the end stage renal disease (ERSD) population. Older renal transplant recipients experience fewer acute rejection episodes than do younger patients. Despite this, death censored graft survival is no better in these older transplant recipients than in younger recipients. We examined the United States Renal Data System (USRDS) database to determine whether recipient age itself has an independent effect on the development of chronic allograft failure (CAF). METHODS: We analyzed 59,509 patients from the files of the USRDS. To determine whether age was an independent risk factor for CAF, the population was analyzed separately for Caucasians, African-Americans, and other ethnic groups. All renal transplant recipients from 1988 to 1997 were examined. Both univariate and multivariate analysis were performed using chronic allograft failure as the outcome of interest. RESULTS: Actuarial 8-year censored graft survival was significantly decreased in the older age groups 67% for ages 18-49 vs. 61.8% for ages 50-64 vs. 50.7% for ages 65+ (P<0.001). In the multivariate analysis, recipient age was a strong and independent risk factor for the development of chronic allograft failure in Caucasians (RR 1.29 for ages 50-64, RR 1.67 for ages older than 65). These findings were reinforced by an analysis that was restricted to living donor transplants without acute rejection. CONCLUSION: In Caucasians increased recipient age is an independent risk factor for the development of chronic renal allograft failure.
Asunto(s)
Envejecimiento/fisiología , Rechazo de Injerto/etiología , Rechazo de Injerto/fisiopatología , Trasplante de Riñón/inmunología , Adulto , Anciano , Población Negra , Cadáver , Enfermedad Crónica , Femenino , Humanos , Donadores Vivos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Donantes de Tejidos , Trasplante Homólogo/inmunología , Población BlancaRESUMEN
INTRODUCTION: African-American renal transplant recipients tend to experience more acute rejection episodes and have shorter graft survival than Caucasian renal transplant recipients. Various factors have been posited to be responsible for this difference, including relative under immunosuppression. We reasoned that by looking at the balance of acute rejections versus death due to infection, we could ascertain whether African-American renal recipients might have more reserve to tolerate an increase in pharmacological immunosuppression. METHODS: We analyzed the United States Renal Data System (USRDS) data from 1987 to 1997 regarding acute rejection episodes and infectious deaths. All other pertinent factors were gathered for a multivariate analysis. A total number of 68,885 adult renal transplant recipients were analyzed. RESULTS: When corrected for all covariates, the relative risk for acute rejection (1.3) was higher although the relative risk for infectious death was lower (0.7) in African-Americans as compared with Caucasians (P<0.01). CONCLUSION: Our study would indicate that relative to Caucasians, African-American renal transplant recipients are at decreased risk for infectious death and therefore may tolerate the more intensive immunosuppression that may be necessary to narrow the gap in acute rejection rates between African-Americans and Caucasian renal transplant recipients.
Asunto(s)
Población Negra , Trasplante de Riñón/mortalidad , Adulto , Infecciones Bacterianas/etiología , Enfermedad Crónica , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Modelos Logísticos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Población Blanca , Infección de Heridas/epidemiologíaRESUMEN
BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation. We evaluated mortality risks associated with SPK, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. METHODS: A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. RESULTS: Adjusted 10-year patient survival was 67% for SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001). The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was 2-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001). However, the adjusted 5-year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients > or =50 years old (RR=1.38, P=0.81). CONCLUSIONS: Among patients with type 1 DM with end-stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis.
Asunto(s)
Trasplante de Riñón/mortalidad , Trasplante de Páncreas/mortalidad , Adulto , Creatinina/orina , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Tasa de SupervivenciaRESUMEN
BACKGROUND: Mycophenolate Mofetil (MMF) has been shown to significantly decrease the number of acute rejection episodes in renal transplant recipients during the 1st year. A beneficial effect of MMF on long-term graft survival has been more difficult to demonstrate. This beneficial effect has not been detected, despite the impact of acute rejection on the development of chronic allograft nephropathy and experimental evidence that MMF may have a salutary effect on chronic allograft nephropathy independent of that of rejection. METHODS: Data on 66,774 renal transplant recipients from the U.S. renal transplant scientific registry were analyzed. Patients who received a solitary renal transplant between October 1, 1988 and June 30, 1997 were studied. The Cox proportional hazard regression was used to estimate relevant risk factors. Kaplan-Meier analysis was performed for censored graft survival. RESULTS: MMF decreased the relative risk for development of chronic allograft failure (CAF) by 27% (risk ratio [RR] 0.73, P<0.001). This effect was independent of its outcome on acute rejection. Censored graft survival using MMF versus azathioprine was significantly improved by Kaplan-Meier analysis at 4 years (85.61% v. 81.9%). The effect of an acute rejection episode on the risk of developing CAF seems to be increasing over time (RR=1.9, 1988-91; RR=2.9, 1992-94; RR=3.7, 1995-97). CONCLUSION: MMF therapy decreases the risk of developing CAF. This improvement is only partly caused by the decrease in the incidence of acute rejection observed with MMF; but, is also caused by an effect independent of acute rejection.
Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Enfermedad Aguda , Azatioprina/uso terapéutico , Rechazo de Injerto/etiología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Ácido Micofenólico/uso terapéutico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Trasplante HomólogoRESUMEN
From the early 1960s, the mainstay of immunosuppression for kidney transplantation has been corticosteroids. Since then, many new drugs have been developed to maintain the renal allograft. Current maintenance immunosuppression commonly consists of corticosteroids, antiproliferative agents and calcineurin inhibitors (e.g. cyclosporin). More recently, antihuman antibodies, either monoclonal or polyclonal, have been developed to use for induction at the time of transplantation or to treat rejection. With the advances in molecular technology, a new class of antihuman antibodies [the anti-interleukin-2 receptor (IL-2R) antibodies] has emerged that incorporate a murine antigen-binding site on to a human immunoglobulin backbone. Such methodology creates antihuman antibodies with high affinity for the epitope and with prolonged serum antibody half-lives. Interleukin-2 and its receptor are central to lymphocyte activation and are the main targets of calcineurin inhibitors. In addition, the anti-IL-2R antibodies inhibit a key target in immune activation. Daclizumab and basiliximab have been shown to significantly reduce the incidence of acute rejection in kidney transplantation. Since these anti-IL-2R antibodies are well tolerated and since calcineurin inhibitors are intrinsically nephrotoxic, anti-IL-2R antibodies have been used in an attempt to avoid cyclosporin after transplantation. Data from clinical trials seem to indicate that the addition of an anti-IL-2R antibody is not sufficient to warrant complete withdrawal of calcineurin inhibitors for more than a very short period after transplantation. A more promising role for anti-IL-2R antibodies may be in renal transplant recipients with delayed graft function (DGF). Recent data on the use of either low-dose calcineurin inhibitors or sirolimus (rapamycin) in conjunction with the anti-IL-2R antibodies for patients with DGF showed no increased risk of acute rejection. Long-term graft survival with use of these low-dose calcineurin inhibitor protocols has yet to be established.
Asunto(s)
Anticuerpos/fisiología , Trasplante de Riñón/inmunología , Receptores de Interleucina-2/inmunología , Animales , Anticuerpos/uso terapéutico , Anticuerpos Monoclonales/fisiología , Anticuerpos Monoclonales/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Receptores de Interleucina-2/antagonistas & inhibidoresRESUMEN
BACKGROUND: Limited long-term data exist on US kidney transplant patients who have received everolimus at time of transplantation. METHODS: Using data from the United Network for Organ Sharing/Organ Procurement Transplant Network database, we described patient characteristics and outcomes among adult patients who received a kidney transplant between 1998 and 2007 and received everolimus maintenance immunosuppression (n = 392) at time of discharge. Outcomes included acute rejection, new-onset diabetes posttransplant, primary graft failure, and serum creatinine. We included single-organ, first-time transplants between 1998 and 2007 as a reference group. RESULTS: Primary graft survival at 3 and 5 years posttransplantation was 87.2% ± 2.1% (95% confidence interval [CI]: 82.5%-90.7%) and 77.4% ± 3.0% (95% CI: 70.8%-82.7%), respectively, in the everolimus-treated group. Improved graft survival with everolimus seemed to be more pronounced in recipients of deceased donor transplants despite the fact that everolimus-treated patients quantitatively had a higher rate of acute rejection at 3 years posttransplant versus the reference group. CONCLUSION: Although the incidence of acute rejection was slightly higher in the everolimus-treated patients, graft survival at 3 and 5 years posttransplantation favored everolimus, with the effect being particularly notable in the recipients who received deceased donor renal transplants.