RESUMEN
The selectin antagonist known as recombinant P-selectin glycoprotein ligand IgG (rPSGL-Ig) blocks leukocyte adhesion and protects against transplantation ischemia reperfusion injury (IRI) in animal models. This randomized (1:1) single-center double-blind 47-patient phase 2 study with 6-month follow-up assessed rPSGL-Ig's safety and impact on early graft function at 1 mg/kg systemic dose with pretransplant allograft ex vivo treatment in deceased-donor liver transplant recipients. Safety was assessed in all patients, whereas efficacy was assessed in a prospectively defined per-protocol patient set (PP) by peak serum transaminase (TA) and bilirubin values, and normalization thereof. In PP patients, the incidence of poor early graft function (defined as peak TA >2500 U/L or bilirubin >10 mg/dL), average peak liver enzymes and bilirubin, normalization thereof and duration of primary and total hospitalization trended consistently lower in the rPSGL-Ig group compared to placebo. In patients with donor risk index above study-average, normalization of aspartate aminotransferase was significantly improved in the rPSGL-Ig group (p < 0.03). rPSGL-Ig treatment blunted postreperfusion induction versus placebo of IRI biomarker IP-10 (p < 0.1) and augmented cytoprotective IL-10 (p < 0.05). This is the first clinical trial of an adhesion molecule antagonist to demonstrate a beneficial effect on liver transplantation IRI and supported by therapeutic modulation of two hepatic IRI biomarkers.
Asunto(s)
Rechazo de Injerto/prevención & control , Trasplante de Hígado , Glicoproteínas de Membrana/farmacología , Proteínas Recombinantes/farmacología , Daño por Reperfusión/prevención & control , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Interleucina-10/metabolismo , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Many factors interact to determine genetic structure within populations including adult density, the mating system, colonization history, natural selection, and the mechanism and spatial patterns of gene dispersal. We examined spatial genetic structure within colonizing populations of Quercus rubra seedlings and Pinus strobus juveniles and adults in an aspen-white pine forest in northern Michigan, USA. A 20-year spatially explicit demographic study of the forest enables us to interpret the results in light of recent colonization of the site for both species. We assayed 217 Q. rubra seedlings and 171 P. strobus individuals at 11 polymorphic loci using nine allozyme systems. Plant genotypes and locations were used in an analysis of spatial genetic structure. Q. rubra and P. strobus showed similar observed levels of heterozygosity, but Q. rubra seedlings have less heterozygosity than expected. Q. rubra seedlings show spatial genetic clumping of individuals on a scale to 25 m and levels of genetic relatedness expected from the clumped dispersion of half-siblings. In contrast, P. strobus has low levels of genetic relatedness at the smallest distance class and positive spatial genetic structure at scales < 10 m within the plot. The low density of adult Q. rubra outside the study plot and limited, spatially clumped rodent dispersal of acorns is likely responsible for the observed pattern of spatial genetic structure and the observed heterozygote deficit (i.e. a Wahlund effect). We attribute weaker patterns observed in P. strobus to the longer dispersal distance of seeds and the historical overlap of seed shadows from adults outside of the plot coupled with the overlap of seed shadows from younger, more recently established reproductive adults. The study demonstrates the utility of long-term demographic data in interpreting mechanisms responsible for generating contemporary patterns of genetic structure within populations.
Asunto(s)
Pinus/enzimología , Pinus/genética , Quercus/enzimología , Quercus/genética , Variación Genética , Pinus/fisiología , Hojas de la Planta/enzimología , Quercus/fisiología , Reproducción , Plantones/enzimologíaAsunto(s)
Anemia/inducido químicamente , Antígenos CD55/genética , Ciclofosfamida/efectos adversos , Supervivencia de Injerto/fisiología , Trasplante de Corazón/inmunología , Trasplante de Riñón/inmunología , Complicaciones Posoperatorias/sangre , Animales , Animales Modificados Genéticamente , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos CD55/inmunología , Hemoglobinas/metabolismo , Humanos , Inmunosupresores/efectos adversos , Macaca fascicularis , Masculino , Porcinos , Factores de Tiempo , Trasplante HeterólogoRESUMEN
A novel bioequivalence testing approach was used to determine intrasubject variability and switchability of two ciclosporin formulations, SangCya (test) and Neoral (reference). Twenty healthy volunteers were enrolled into a single-dose, randomized, open-label, 4-period, 2-sequence study with a crossover replicate design. Subject-by-formulation interaction variances were compared using a mixed effects linear model. Intrasubject variability for ln AUC(0-infinity) and ln C(max) of SangCya and Neoral were not significantly different. The 95% confidence intervals of the intrasubject variability of AUC(0-infinity) (0.94) and C(max) (1.28) as determined using the bootstrap nonparametric percentile method (n = 2,000) were below the individual bioequivalence limit estimated at 2.25. We concluded equivalent intrasubject variability of ciclosporin pharmacokinetics and switchability between SangCya and Neoral.
Asunto(s)
Ciclosporina/farmacocinética , Inhibidores Enzimáticos/farmacocinética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Equivalencia TerapéuticaAsunto(s)
Intestino Delgado/trasplante , Protoporfirinas/uso terapéutico , Daño por Reperfusión/prevención & control , Trasplante Isogénico/fisiología , Animales , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Preservación de Órganos , Premedicación , Ratas , Ratas Endogámicas Lew , Donantes de Tejidos , Trasplante Isogénico/patologíaRESUMEN
BACKGROUND: Recently, peptides derived from the heavy chain of HLA-B2702 have been shown to modulate immune responses. In this study, we examined the use of these peptides for immunosuppression in a pig to mouse islet xenograft model. METHODS: Purified porcine islets were transplanted in autoimmune (non-obese diabetic) and non-autoimmune (streptozotocin-injected CBA or C57/Bl6) diabetic mice. Various dosing regimens of HLA-derived peptides with and without antilymphocyte therapy were administered to recipient mice. Graft rejection was determined by daily serum glucose determinations, and, at selected time points, grafts were removed to demonstrate function and provide immunohistochemical examination. RESULTS: HLA-derived peptides were demonstrated to prolong graft survival in both pretransplant and posttransplant treatment regimens. This effect was increased with concomitant antilymphocyte therapy. CONCLUSIONS: Further elucidation of the mechanism of action of these immunomodulatory peptides may help in the development of novel immunosuppressive protocols.
Asunto(s)
Trasplante de Islotes Pancreáticos/inmunología , Trasplante Heterólogo , Adyuvantes Inmunológicos/uso terapéutico , Animales , Suero Antilinfocítico/uso terapéutico , Supervivencia de Injerto/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/fisiología , Antígenos de Histocompatibilidad/uso terapéutico , Inmunosupresores/uso terapéutico , Ratones , Ratones Endogámicos CBA , Ratones Endogámicos NOD , Porcinos , Regulación hacia ArribaAsunto(s)
Supervivencia de Injerto/inmunología , Intestino Delgado/trasplante , Prueba de Cultivo Mixto de Linfocitos , Complejo Mayor de Histocompatibilidad , Péptidos/uso terapéutico , Trasplante Homólogo/inmunología , Animales , Ciclosporina/uso terapéutico , Terapia de Inmunosupresión/métodos , Isoantígenos/inmunología , Transfusión de Linfocitos , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas Lew , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Rechazo de Injerto/terapia , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Enfermedad Aguda , Adolescente , Adulto , Anciano , Animales , Suero Antilinfocítico/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , ConejosRESUMEN
Post-transplantation lymphoproliferative disorders (PTLD) are a clinicopathologically heterogeneous group of lymphoid proliferations. The majority are of B-cell origin and associated with Epstein-Barr virus (EBV) infection. In contrast, the development of T-cell PTLD is much less common and EBV does not appear to be involved in pathogenesis. In this report we describe three patients who developed large granular lymphocyte (LGL) leukaemia after renal transplantation. These patients had clonal expansion of CD3+, CD8+, CD57+, CD56- LGL. We were unable to detect CMV antigen or find evidence for EBV or human T-cell leukaemia/lymphoma virus genome in the LGL from these patients. These data show that LGL leukaemia should be included as one of the types of T-cell proliferations which can occur post transplant.
Asunto(s)
Trasplante de Riñón/efectos adversos , Leucemia Linfoide/virología , Adulto , Anciano , Antígenos CD/análisis , Western Blotting , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/complicaciones , ADN Viral/análisis , Femenino , Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T , Genoma Viral , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-II/complicaciones , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Virus Linfotrópico T Tipo 2 Humano/aislamiento & purificación , Humanos , Terapia de Inmunosupresión/efectos adversos , Masculino , Infecciones Oportunistas/complicaciones , Receptores de Antígenos de Linfocitos T/análisisRESUMEN
BACKGROUND: Treatment of fetal pancreas (FP) isografts with insulin-like growth factor-I greatly improves the rate of conversion to euglycemia in diabetic rats. Complete knowledge of other factors that may facilitate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers. ALR has trophic effects on regenerating liver. We studied the effects of in situ administration of this agent on FP isografts in rats. METHODS: Streptozotocin-diabetic Lewis rats (blood glucose > 300 mg/dl) received 16 FP isografts transplanted intramuscularly. ALR was delivered from day 1 through day 14, in doses of 40 or 400 ng/kg/d. Animals were followed for 3 months with serial weights and blood glucose monitoring. These animals were compared with those treated with vehicle alone. RESULTS: Of the group treated with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) were euglycemic (P=0.0003). Of the group treated with ALR at 400 ng/kg/day for 14 days, 88% (seven of eight) were euglycemic (P=0.0007). Of the group treated with vehicle alone, none of the six were euglycemic. Euglycemia is defined here as glucose < 200 mg/dl for 3 days. Pathology of the intramuscular transplant site showed patches of islet tissue embedded in fat. These patches demonstrated insulin immunoreactivity. CONCLUSIONS: Diabetes was reversed in a significantly greater proportion of FP + ALR-treated recipients than those animals treated with vehicle alone. Local delivery of growth factors may be used as an adjunct to FP transplantation to improve the rate of success. This in situ model may be useful to further evaluate other soluble factors.
Asunto(s)
Sustancias de Crecimiento/farmacología , Trasplante de Islotes Pancreáticos , Regeneración Hepática , Páncreas/embriología , Proteínas , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/terapia , Factor I del Crecimiento Similar a la Insulina/farmacología , Páncreas/patología , Ratas , Ratas Endogámicas LewRESUMEN
We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable. A renal biopsy showed massive tubular necrosis associated with a prominent granulomatous reaction. The process had a striking regional distribution within the kidney with the injury and inflammation limited to the outer medulla. Adenovirus type 11 was isolated from renal tissue by culture, and adenovirus was demonstrated by immunofluorescence and electron microscopy in the kidney biopsy. Immunosuppression may result in unusual patterns of response to infectious agents. This case demonstrated tropism of the adenovirus to only selected tubules within the kidney, with sparing of other organ function including, specifically, the pancreas allograft. The differential diagnosis of a granulomatous reaction in the transplant kidney must be expanded to include viral infection, in particular, adenovirus.
Asunto(s)
Infecciones por Adenovirus Humanos/complicaciones , Trasplante de Riñón , Trasplante de Páncreas , Complicaciones Posoperatorias/virología , Infecciones por Adenovirus Humanos/patología , Adulto , Diabetes Mellitus Tipo 1/cirugía , Retinopatía Diabética/complicaciones , Diagnóstico Diferencial , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Riñón/patología , Riñón/virología , Enfermedades Renales/diagnóstico , Trasplante de Riñón/patología , Túbulos Renales/ultraestructura , Microscopía Electrónica , Páncreas/patología , Páncreas/virología , Trasplante de Páncreas/patologíaRESUMEN
Previous reports from other investigators demonstrate prolongation of allogeneic heart graft survival and decrease in CTL responses in rats treated with a small synthetic peptide corresponding to residues 75-84 of the human HLA-B7-01 molecule (Allotrap 07R). We wished to determine the efficacy of these peptides in the highly immunogenic ACI > LEW and LEW > ACI small bowel transplant models. Animals were divided into treatment groups: I, none; II, Allotrap (20 mg/kg/day on Days 0-4); III, cyclosporine (CsA; 10 mg/kg/day on Days 0-4); IV, Allotrap + CsA (as in groups II and III); V, Allotrap (40 mg/kg/day every other day on Days -19 to 4); VI, Allotrap + CsA (as in groups III and V); VII, Allotrap + CsA (as in groups III and V, with Allotrap administered intragraft Days 0-4). The animals were sacrificed at the time of graft rejection (defined by dusky, necrotic stoma and increased stomal output). Peripheral blood, spleen, native bowel, and allograft intraepithelial and lamina propria lymphocytes were harvested and mixed lymphocyte culture (MLC) reactivity against self, donor, and third-party splenocytes was assessed. Statistical analysis was performed by ANOVA with Dunnett's t for multiple comparisons against a control as a post hoc test. We found a very slight, but significant prolongation of graft survival in with treatment protocol V for both strain combinations. In addition, MLC response of splenocytes to donor antigen was decreased with combined CsA and Allotrap, but not with Allotrap alone. We conclude that Allotrap decreases response to alloantigens, and slightly, but significantly prolongs graft survival in the hihgly immunogenic small bowel transplant model.
Asunto(s)
Supervivencia de Injerto/efectos de los fármacos , Intestino Delgado/trasplante , Péptidos/farmacología , Animales , Rechazo de Injerto/tratamiento farmacológico , Antígenos de Histocompatibilidad Clase I/farmacología , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas Lew , Trasplante HomólogoAsunto(s)
Diabetes Mellitus Experimental/cirugía , Supervivencia de Injerto , Antígenos de Histocompatibilidad Clase I/inmunología , Trasplante de Islotes Pancreáticos/inmunología , Péptidos/uso terapéutico , Trasplante Heterólogo/inmunología , Animales , Glucemia/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/sangre , Ratones , Ratones Endogámicos CBA , Ensayo de Capsula Subrrenal , Porcinos , Factores de Tiempo , Trasplante Heterólogo/fisiologíaAsunto(s)
Trasplante de Tejido Fetal , Supervivencia de Injerto , Terapia de Inmunosupresión/métodos , Trasplante de Islotes Pancreáticos/fisiología , Trasplante de Hígado , Trasplante de Páncreas , Trasplante Heterólogo/fisiología , Animales , Glucemia/metabolismo , División Celular , Técnicas de Cocultivo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/cirugía , Islotes Pancreáticos/citología , Masculino , Ratones , Ratones Endogámicos CBA , Ensayo de Capsula Subrrenal , Porcinos , Trasplante IsogénicoRESUMEN
Transplantation of fetal pancreas (FP) is a potential treatment for diabetes mellitus. FP has remarkable proliferative capacity and may be induced to expand sufficiently to provide a functional beta cell mass in adult recipients. We have demonstrated that local delivery of recombinant insulin-like growth factor-I (IGF-I) onto FP isografts is sufficient to reverse streptozotocin-induced diabetes in animals receiving as few as 4 fetal pancreata. In this current study we investigated other regimens of IGF-I delivery in an attempt to define whether its effects on FP required local delivery or whether other, more clinically feasible, forms of treatment would suffice. In our model, diabetic Lewis rats received isografts of 16 FP into the anterior thigh intramuscular (IM) site. In the group of FP recipients treated with vehicle alone, no animals converted to euglycemia (0/8). When the IM site was pretreated locally with 14 days of continuous IGF-I administration (69 micrograms/kg per day) prior to FP transplantation, 100% of the recipients (10/10) became euglycemic with a mean interval from transplant to euglycemia of 35 +/- 15 days (P < 0.001 when compared to vehicle alone). No significant advantage over the vehicle alone group was gained either when the FP tissue was cultured for 48 hr in the presence of IGF-I (100 micrograms/ml) and then implanted (27% conversion to euglycemia, 3/11) or when FP isografts were treated with continuous subcutaneous delivery of IGF-I (69 micrograms/kg per day over 14 days) distant from the transplant site (0% conversion to euglycemia, 0/6). IGF-I increased the rate of conversion to euglycemia either when delivered locally to FP isografts or when delivered to the transplant bed prior to transplantation. This suggests an active role of the IGF-I-treated transplant bed in the success of FP transplantation.
Asunto(s)
Diabetes Mellitus Experimental/cirugía , Trasplante de Tejido Fetal , Supervivencia de Injerto/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Trasplante de Páncreas/fisiología , Animales , Glucemia/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/prevención & control , Femenino , Masculino , Páncreas/embriología , Trasplante de Páncreas/patología , Embarazo , Ratas , Proteínas RecombinantesAsunto(s)
Intestino Delgado/trasplante , Trasplante Homólogo/inmunología , Trasplante Homólogo/métodos , Anastomosis Quirúrgica , Animales , Aorta Abdominal/cirugía , Ciclosporina/uso terapéutico , Hurones , Supervivencia de Injerto/inmunología , Enfermedad Injerto contra Huésped , Humanos , Inmunosupresores/uso terapéutico , Recién Nacido , Masculino , Arteria Mesentérica Superior/cirugía , Vena Porta/cirugía , Trasplante Heterotópico , Trasplante Homólogo/patologíaAsunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Trasplante de Riñón/efectos adversos , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Trasplante de Páncreas/efectos adversos , Adulto , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/cirugía , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/cirugía , Femenino , Rechazo de Injerto/etiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Humanos , MasculinoRESUMEN
Portal venous (PV) injection of alloantigen can result in tolerance. We have previously reported that this effect is abrogated by pretreatment with gadolinium (Gd), an element known to inhibit Kupffer cell phagocytosis. To further elucidate the role of Kupffer cells (KC) in PV tolerance, the present study examined the ability of KC to present alloantigen in vitro to syngeneic responder lymphocytes after in vivo PV administration of alloantigen with or without pretreatment with Gd. Wistar Furth (WF) rats were pretreated 24 hr prior to KC harvest with a PV injection of 1 x 10(7) allogeneic Lewis (LEW) rat lymphocytes (KC-L) or saline (KC-N). Another group received Gd intravenously 24 h prior to the PV injection of LEW cells (KC-L + Gd). KC were isolated from the WF rats using collagenase digestion and Percoll (90% pure by morphologic criteria and by monoclonal antibodies KU-1 and ED-2). Responder WF lymphocytes were cocultured with media alone, or with KC as prepared above, for 72 hr. KC-L demonstrated significant stimulation of the WF responders (P = 0.02 vs KC-N). Gd abrogated this stimulation (P = 0.04, KC-L vs KC-L + Gd) but not by nonspecific inhibition of the cocultures (KC-N vs KC-L + Gd, P > 0.05, no difference). This study demonstrates that KC can effectively present PV alloantigen for the activation of naive syngeneic T lymphocytes, thereby further supporting the hypothesis that KC play an integral role in the induction of PV tolerance by presentation of antigen to responder T cells.
Asunto(s)
Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Gadolinio/farmacología , Isoantígenos/inmunología , Macrófagos del Hígado/efectos de los fármacos , Macrófagos del Hígado/inmunología , Animales , Células Cultivadas , Inyecciones Intravenosas , Prueba de Cultivo Mixto de Linfocitos , Transfusión de Linfocitos , Masculino , Vena Porta , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Bazo/citologíaRESUMEN
Within the past year at our transplant center we have had the experience of performing renal allografts in two patients older than 65 years, each of whom had been on hemodialysis more than 10 years. Both resulted in patient mortality within 90 days of transplant (one due to myocardial infarction, the other due to visceral ischemia with infarction). This prompted us to review retrospectively our own data (n = 204) and the national (UNOS) data (n = 10,971) regarding transplant outcome, patient age, and length of time on dialysis prior to renal transplantation. This review revealed that patient mortality after transplant increased with the length of end-stage renal disease (dialysis, regardless of type) independent of age, the greatest mortality occurring within the first 6 months of transplant (and not thereafter); graft survival was similar for all age cohorts analyzed. Our review of the literature reveals a paucity of articles pertaining to post-transplant mortality and length of time on dialysis prior to transplant. Our results indicate the following possible conclusions. (1) The length of time of end-stage renal disease therapy prior to renal transplantation is a significant and independent risk factor for post-transplant mortality. (2) Higher priority should be given to this factor when formulating strategies for allocation of scarce resources. (3) Patients on dialysis for extended periods of time who are elderly may be at particularly high risk. (4) Patients being considered for renal transplant should be informed of their individual risk factors for mortality post-transplant based on length of ESRD therapy. (5) Renal transplantation should be considered as early as possible in patients with ESRD (or imminent ESRD).