RESUMEN

Despite significant advancements in clinical transplantation, very few reports describe the long-term acceptance of transplanted solid organs without indefinite immunosuppression. The immunosuppressive agents used are nonspecific and have serious potential side effects. We present a patient who received a living-donor renal allograft from the same person who had donated bone marrow to her several years earlier. Tolerance was expected based on previous acceptance of full-thickness skin grafts from the donor. Indeed, there has been no evidence of rejection during a 6-year follow-up period, and no induction or maintenance immunosuppression has been given. All noninvasive parameters of graft function remain normal. This and similar reports prove that genetically disparate solid organs can coexist without pharmacological immunosuppression.

Asunto(s)

Trasplante de Médula Ósea/inmunología , Tolerancia Inmunológica , Trasplante de Riñón/inmunología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Donadores Vivos , Piel/patología , Trasplante de Piel/inmunología , Factores de Tiempo , Trasplante Homólogo

RESUMEN

UNLABELLED: It has been routine at the University of Alabama Medical Center to obtain a radionuclide renal function study immediately after transplantation (usually within 3 d) that includes estimation of effective renal plasma flow (ERPF) from a single plasma sample in addition to imaging. We present here the correlation between baseline measurements and the 1-y graft survival. METHODS: Two cohort years were reviewed: 1988, when 131I-orthoiodohippurate (OIH) was used; and 1995, when 99mTc-mercaptoacetyltriglycine (MAG3) was used. ERPF was measured concurrently with gamma-camera imaging by previously published single-injection, single-sample methods (converting MAG3 clearance to ERPF by means of a correction factor). RESULTS: Graft survival during the first postoperative year improved significantly in the interval between cohort years, from 74% of 147 cadaver (CD) grafts in 1988 to 91% of 200 CD grafts in 1995 (log rank test, P < 0.05). In contrast, for living related donor (LRD) grafts there was no significant change, from 91% of 66 in 1988 to 91% of 83 in 1995. The baseline ERPF was a significant predictor of graft survival in both 1988 and 1995 (Wilcoxon test, P > 0.05). For LRD grafts the association was not significant in either year. Using MAG3 (1995), the peak time and the ratio of counting rate (R) at 20 min to that at 3 min (R20:3) were also significant predictors for CD graft survival. Using OIH (1988 cohort), the correlation with peak time did not reach significance, and the R20:3 measurement was not available. Although multivariate combinations (Cox proportional hazards model) did not have significantly more predictive value at the 95% confidence level than ERPF or R20:3 alone, some statisticians suggest a 75% confidence level for adding an additional covariate to a multivariate model. Use of this level led to a model including both ERPF and R20:3. CONCLUSION: Single-sample ERPF measured in the immediate post-transplant period, whether from OIH clearance or MAG3 clearance, was a statistical predictor of graft survival for CD transplants. For MAG3, the peak time and R20:3 were also significant predictors. These associations held only for CD transplants and not for LRD transplants.

Asunto(s)

Supervivencia de Injerto , Trasplante de Riñón/fisiología , Radiofármacos , Circulación Renal , Estudios de Cohortes , Humanos , Radioisótopos de Yodo , Ácido Yodohipúrico/farmacocinética , Pruebas de Función Renal/métodos , Trasplante de Riñón/mortalidad , Tasa de Depuración Metabólica , Valor Predictivo de las Pruebas , Cintigrafía , Radiofármacos/farmacocinética , Flujo Sanguíneo Regional , Estudios Retrospectivos , Tasa de Supervivencia , Tecnecio Tc 99m Mertiatida/farmacocinética

RESUMEN

BACKGROUND: Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation pulsatile perfusion (PP) versus cold storage (CS) is debated. METHODS: Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( < or = 20 min, 21-40 min, or > 40 min) and total ischemic time (TIT) ( < or > or = 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. RESULTS: There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). CONCLUSIONS: Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

Asunto(s)

Supervivencia de Injerto , Trasplante de Riñón , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Adenosina , Adulto , Alopurinol , Cadáver , Soluciones Cardiopléjicas , Frío , Estudios de Seguimiento , Glutatión , Humanos , Insulina , Flujo Pulsátil , Rafinosa

RESUMEN

BACKGROUND: The beneficial effects of donor specific transfusion (DST) have become controversial in the cyclosporine era. This study was performed to evaluate the potential benefits of a new protocol for administering DSTs in the perioperative period. METHODS: Non-HLA identical living donor kidney transplant recipients were randomized prospectively to control or to receive a DST 24 hr before transplant and 7-10 days posttransplant. All patients received similar immunosuppression according to protocol. RESULTS: The protocol had 212 evaluable patients (115 transfused and 97 control). There were no differences in 1- and 2-year graft and patient survival, causes of graft failure, incidence and types of infection, repeat hospitalization, or the ability to withdraw steroids. Immunological hyporesponsiveness (by mixed lymphocyte culture) occurred more frequently in transfused patients (18%) than controls (3%) (P = 0.04). Blood stored for > or =3 days was associated with fewer early rejections than blood stored < or =2 days. Overall, class II antigen mismatches were associated with more rejection episodes than class I antigen mismatches. However, transfused patients, but not control patients, with more class I antigen mismatches were more likely to have rejections. CONCLUSIONS: Administration of DSTs by the method described had no practical influence on patient or graft survival for up to 2 years. However, donor-specific hyporesponsiveness was more common in transfused patients (18 vs. 3%). Longer follow-up will be needed to determine whether DST will be associated with long-term benefit.

Asunto(s)

Transfusión Sanguínea , Ciclosporina/uso terapéutico , Prueba de Histocompatibilidad , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Donadores Vivos , Cuidados Posoperatorios , Cuidados Preoperatorios , Conservación de la Sangre , Femenino , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Antígenos de Histocompatibilidad Clase I/análisis , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Masculino , Estudios Prospectivos , Análisis de Supervivencia , Factores de Tiempo

RESUMEN

BACKGROUND AND OBJECTIVE: Cardiac disease is a common cause of death in renal transplant recipients. This study retrospectively analyzes the results of myocardial revascularization procedures in these patients and makes recommendations for managing coronary atherosclerosis in patients with renal disease who already have a transplanted kidney or who may receive a kidney transplant. METHODS: Patients who had myocardial revascularization (coronary artery bypass grafting [CABG] or percutaneous transluminal coronary angioplasty [PTCA]) and renal transplantation at the authors' institution between 1968 and 1994 were analyzed. Patient, procedural, and institutional variables were used for actuarial analyses of survival, as well as multivariate analyses of risk factors for death. RESULTS: Eighty-three of 2989 renal transplant patients required myocardial revascularization either before or after their transplant, and diabetes mellitus was the cause of renal failure in 42% of these patients. Standard coronary angiography, CABG, and PTCA techniques were used without periprocedural renal allograft loss. Actuarial patient survival was 89%, 77%, and 65% at 1, 3, and 5 years after the last procedure (transplantation or revascularization). Cardiac disease was the most common mode of death. Early-phase risk factors for death by multivariate analysis included hypertension and revascularization before 1989. Late-phase risk factors for death included diabetes mellitus, higher number of pre-CABG myocardial infarctions, renal transplantation before 1984, older age, and unstable angina before CABG. CONCLUSIONS: Myocardial revascularization can be performed with acceptable short- and long-term results in patients with renal disease who have renal transplantation either before or after the revascularization procedure. Diabetes mellitus was a highly prevalent condition among these patients, and cardiac disease was their most common mode of death. PTCA and CABG, as performed at this institution, posed little risk for renal allograft loss. Modification of risk factors for coronary atherosclerosis, rigorous cardiac evaluation of patients at risk for coronary artery disease before renal transplantation, and aggressive use of revascularization procedures to decrease the incidence of myocardial infarction are proposed as ways to prolong the survival of renal transplant patients with ischemic heart disease.

Asunto(s)

Enfermedad de la Arteria Coronaria/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Revascularización Miocárdica , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Revascularización Miocárdica/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

PURPOSE: Renal transplantation is safe and effective for end stage renal disease in children with posterior urethral valves. We previously reported our 5-year post-transplantation results in boys with posterior urethral valves and matched controls. Graft survival was similar. However, we were concerned about elevated serum creatinine and the potential detrimental effects of hostile bladder dynamics in these children. We performed this study to determine whether our concern would be substantiated. MATERIALS AND METHODS: We retrospectively analyzed the clinical records and computerized transplantation database in 268 boys younger than 19 years who underwent renal transplantation from May 1968 through November 1988. The 18 children with posterior urethral valves were compared to a nonobstructed cohort of 18 boys in regard to age, number of transplants, donor type and immunosuppression. All children had at least 10 years of followup (range 10 to 19). RESULTS: The 10-year post-transplant patient survival in the posterior urethral valves and control groups was 94 and 100%, while 10-year graft survival was 54 and 41%, respectively. There was no statistically significant difference in graft survival when comparing immunosuppression type, donor source and pre-transplant proximal urinary diversion. The 10-year mean serum creatinine was 2.3 and 2.0 mg./dl. in the posterior urethral valve and control groups, respectively (not statistically significant). CONCLUSIONS: Our renal transplantation results in children with posterior urethral valves are comparable to those in children with nonobstructive end stage renal disease. The 10-year graft survival was better but not statistically significant in the posterior urethral valve group, while serum creatinine was similar. Our concern regarding renal transplantation in children with posterior urethral valves was not substantiated.

Asunto(s)

Fallo Renal Crónico/cirugía , Trasplante de Riñón , Uretra/anomalías , Adolescente , Niño , Preescolar , Creatinina/sangre , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Lactante , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Masculino , Estudios Retrospectivos , Factores de Tiempo

RESUMEN

OBJECTIVE: To review the experience with the operative treatment of tertiary hyperparathyroidism (TH) from a single renal transplant center. SUMMARY BACKGROUND DATA: Most patients with chronic renal failure show evidence of secondary hyperparathyroidism by the time maintenance hemodialysis begins. Persistent secondary hyperparathyroidism (i.e., TH) requiring surgical intervention is uncommon in the authors' experience. METHODS: Charts of patients who underwent parathyroidectomy for TH were reviewed retrospectively. Information obtained included demographics, laboratory data, symptoms, operative procedure (including morbidity and mortality rates), and pathology. Comparisons of demographic data and allograft survival were made between the transplant population as a whole and a matched cohort group of patients. RESULTS: Thirty-eight patients from 4344 renal transplant procedures during a 29-year period required parathyroidectomy for TH. All patients had hypercalcemia; 20 were asymptomatic and 18 had varying symptoms. Mean time from renal transplantation to parathyroidectomy was 997 +/- 184 days, with a mean preoperative calcium level of 12.2 +/- 0.14 mg/dl. Total parathyroidectomy with parathyroid autograft was performed in 26 of 34 primary procedures. There were no deaths. The operative morbidity rate was 6% (wound separation and vocal cord hemiparesis, one each). Pathology was reported in all patients and recently reviewed in 28 patients. Twenty-four had diffuse hyperplasia and nine had nodular hyperplasia; one had an adenoma. Parathyroid glands diagnosed as nodular hyperplasia were significantly larger by total mass than those with diffuse hyperplasia. Comparison of allograft survival between the study group and a matched cohort group of patients revealed no difference in long-term graft survival. CONCLUSIONS: Operative intervention is recommended in patients with an asymptomatic increase in serum calcium to >12.0 mg/dl persisting for >1 year after the transplant, acute hypercalcemia (calcium >12.5 mg/dl) in the immediate posttransplant period, and symptomatic hypercalcemia.

Asunto(s)

Hiperparatiroidismo Secundario/cirugía , Trasplante de Riñón , Paratiroidectomía , Adulto , Estudios de Casos y Controles , Femenino , Supervivencia de Injerto , Humanos , Hipercalcemia/sangre , Hipercalcemia/etiología , Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/patología , Incidencia , Masculino , Registros Médicos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Only half the patients who lost a renal allograft either returned to the waiting list (32%) or were retransplanted (17%). One fifth died soon after allograft loss. Patients did not return to the waiting list for multiple reasons including patient choice, worsened medical condition and most commonly, interest but non-referral. Diabetics had a significantly diminished chance for survival on dialysis after graft loss. African-Americans had a better chance of survival after graft loss but a much worse opportunity to be retransplanted. The use of CellCept in triple immunosuppressive therapy, along with a flow cytometry crossmatch, has improved retransplant allograft survival commensurate with primary graft outcome. The incidence of retransplantation is decreasing at our institution even though the number of potential candidates for retransplantation remains stable.

Asunto(s)

Trasplante de Riñón/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Adulto , Alabama , Población Negra , Cadáver , Femenino , Supervivencia de Injerto , Hospitales Universitarios/estadística & datos numéricos , Humanos , Trasplante de Riñón/mortalidad , Trasplante de Riñón/fisiología , Donadores Vivos/estadística & datos numéricos , Masculino , Reoperación/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Donantes de Tejidos/estadística & datos numéricos , Resultado del Tratamiento , Población Blanca

RESUMEN

Tubular damage and loss associated with interstitial inflammation and fibrosis may be the most important determinants in chronic renal allograft rejection. To elucidate potential pathophysiologic mechanisms associated with tubulointerstitial lesions, we examined the expression of a fibrogenic cytokine, acidic fibroblast growth factor (FGF-1) and its high-affinity receptors, in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy after graft loss, secondary to chronic rejection. In situ hybridization and immunohistochemical analyses demonstrated minimal expression of FGF-1 mRNA and protein in the tubulointerstitial compartment of the normal human kidney. In contrast, tubulointerstitial lesions in kidney allografts experiencing chronic rejection demonstrated the exaggerated appearance of both FGF-1 protein and mRNA in resident inflammatory and tubular epithelial cells. Patterns of staining were consistent throughout tubular compartments and did not appear to be localized to any particular region. The tubulointerstitium in kidneys with findings of chronic rejection also exhibited increased immunodetection of proliferating cell nuclear antigen in the tubular epithelium, inflammatory cell infiltrate, and neovascular structures. The enhanced appearance of FGF-1 and readily detectable fibroblast growth factor receptors suggests that this polypeptide mitogen may serve as an important mediator of growth and repair responses, associated with development of angiogenesis and tubulointerstitial lesions during chronic rejection of human renal allografts.

Asunto(s)

Factor 1 de Crecimiento de Fibroblastos/análisis , Rechazo de Injerto , Trasplante de Riñón , Túbulos Renales/química , Receptores de Factores de Crecimiento de Fibroblastos/análisis , Biomarcadores/análisis , Enfermedad Crónica , Factor 1 de Crecimiento de Fibroblastos/genética , Humanos , Hibridación in Situ , Antígeno Nuclear de Célula en Proliferación/análisis , ARN Mensajero/análisis , Receptores de Factores de Crecimiento de Fibroblastos/genética , Estudios Retrospectivos , Trasplante Homólogo , Factor de von Willebrand/análisis

Asunto(s)

Población Negra , Fallo Renal Crónico/complicaciones , Trasplante de Riñón , Donadores Vivos , Población Blanca , Alabama , Distribución de Chi-Cuadrado , Hospitales Universitarios , Humanos , Fallo Renal Crónico/cirugía , Morbilidad , Selección de Paciente , Probabilidad , Estudios Prospectivos

Asunto(s)

Negro o Afroamericano/estadística & datos numéricos , Supervivencia de Injerto , Trasplante de Riñón/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Listas de Espera , Adulto , Alabama , Cadáver , Femenino , Rechazo de Injerto/epidemiología , Humanos , Trasplante de Riñón/fisiología , Masculino , Estudios Retrospectivos , Factores de Tiempo , Población Blanca/estadística & datos numéricos

RESUMEN

Financial circumstances force some stable renal transplant recipients to discontinue cyclosporine (CsA). Previous results from our center document a subgroup of these patients at increased risk for acute rejection and allograft loss, namely, those of African ancestry. After 1988, such disadvantaged recipients have been able to receive CsA at no charge through the National Organization for Rare Disorders (NORD). At the University of Alabama at Birmingham, 54 patients were enrolled in the NORD program between 1988 and 1994. Acute rejection, allograft survival, and patient survival in these patients were compared with those in 42 patients who, prior to 1988, were withdrawn from CsA for financial reasons. Both groups were similar socioeconomically. The mean follow-up was 69 +/- 33 months (+/-SD) in the withdrawal group and 45 +/- 14 months in those entering the NORD program. Acute rejections occurred with similar frequency in both groups before CsA withdrawal (45%) or NORD enrollment (48%). In contrast, acute rejections were more common in patients after the onset of CsA withdrawal (38%) than after NORD enrollment (11%) (P < 0.01). Black patients withdrawn from CsA experienced more acute rejections than their counterparts in the NORD program (57% v 15%) (P < 0.01). White NORD recipients also experienced fewer acute rejections, although the difference was not statistically significant (withdrawal group 16% v NORD group 4%; P = 0.29). Rejection episodes were accompanied by reduced graft survival in black patients withdrawn from CsA, while significant improvement was seen in those remaining on CsA-based therapy (P < 0.05). No difference in allograft survival was seen among white patients in either group (withdrawal group 74% v NORD group 82%; P = 0.33). Thus, long-term access to CsA through the NORD program reduced acute rejections and improved allograft survival in an economically disadvantaged subgroup of renal transplant recipients. These findings emphasize the importance of continued access to CsA in black renal transplant recipients and its influence on long-term allograft survival.

Asunto(s)

Ciclosporina/uso terapéutico , Trasplante de Riñón , Asistencia Médica , Indigencia Médica , Enfermedad Aguda , Adulto , Negro o Afroamericano/estadística & datos numéricos , Ciclosporina/economía , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Humanos , Trasplante de Riñón/economía , Masculino , Población Blanca/estadística & datos numéricos

Asunto(s)

Técnicas de Transferencia de Gen , Trasplante de Riñón/inmunología , Transfección/métodos , beta-Galactosidasa/biosíntesis , Adenoviridae , Animales , Secuencia de Bases , Cartilla de ADN , Vectores Genéticos , Supervivencia de Injerto , Humanos , Riñón/metabolismo , Trasplante de Riñón/métodos , Trasplante de Riñón/fisiología , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Datos de Secuencia Molecular , Polilisina , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-Dawley , Trasplante Isogénico , beta-Galactosidasa/análisis

RESUMEN

Despite recognition of chronic vasculo-occlusive disease in solid organ transplantation, the exact pathophysiologic events resulting in neointima formation remain to be elucidated. Since acidic fibroblast growth factor (FGF-1) is an established modulator of vascular cell function, we examined the expression of this growth factor and its high affinity receptors in both relevant renal transplant controls (n = 5) and tissue from patients (n = 19) who underwent nephrectomy following graft loss secondary to chronic rejection. In situ hybridization and immunohistochemical studies demonstrated minimal vascular expression and distribution of FGF-1 and FGF high affinity receptors in the normal human kidney. In contrast, vascular lesions in kidney allografts experiencing chronic rejection demonstrated the exaggerated appearance of FGF-1 ligand and receptors. Immunoreactive FGF-1 readily was detected in medial smooth muscle cells and focal areas of intimal hyperplasia, particularly in association with the presence of inflammatory infiltrate. Enhanced staining for FGF-1 mRNA primarily was associated with the appearance of resident inflammatory cells. Medial smooth muscle cells of hyperplastic vascular structures demonstrated the greatest immunoappearance of FGF receptors-however, diffuse immunostaining also was observed in areas of intimal hyperplasia. The enhanced appearance of both FGF-1 and FGF receptors in the vascular wall suggests that this polypeptide mitogen may serve as an important mediator of growth responses associated with neointima development and angiogenesis during chronic rejection of human renal allografts.

Asunto(s)

Vasos Sanguíneos/metabolismo , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Trasplante de Riñón/inmunología , Enfermedades Vasculares Periféricas/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Adulto , Anciano , Vasos Sanguíneos/patología , Niño , Enfermedad Crónica , Femenino , Rechazo de Injerto , Humanos , Inmunohistoquímica , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/patología , Persona de Mediana Edad , Donantes de Tejidos

RESUMEN

Glomerular lesions are considered one of the more detrimental pathologic changes associated with chronic rejection of renal allografts. To elucidate potential pathophysiologic mechanisms associated with transplant glomerulopathy, we examined the expression of acidic fibroblast growth factor (FGF-1) and its high-affinity receptors (FGFR) in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy following graft loss secondary to chronic rejection. In situ immunohistochemical analyses demonstrated minimal staining and distribution of FGFR and FGF-1, which was localized to the mesangial matrix in glomeruli from normal human kidneys. In situ hybridization failed to detect the presence of FGF-1 mRNA in control tissue. In contrast, each stage of the developing glomerular lesion associated with chronic rejection demonstrated the exaggerated appearance of FGF-1 protein in visceral and parietal epithelial cells. Intense staining for FGF-1 protein did not correlate with the increased appearance of FGF-1 mRNA, which was restricted to circulating inflammatory cells. Glomeruli in kidneys with findings of chronic rejection also exhibited increased immunodetection of both FGFR and PCNA in mesangial and epithelial cells. Immunogold labeling of chronically rejected visceral epithelial cells revealed both cytoplasmic and nuclear/localization of FGF-1, thereby establishing mitogenic potential of the growth factor. The enhanced appearance of both biologically active FGF-1 and FGFR suggests that this polypeptide may serve as an important mediator of growth responses associated with glomerular lesion development during chronic rejection.

Asunto(s)

Factor 1 de Crecimiento de Fibroblastos/análisis , Glomerulonefritis/etiología , Glomerulonefritis/patología , Rechazo de Injerto/metabolismo , Glomérulos Renales/patología , Trasplante de Riñón/inmunología , Proteínas Tirosina Quinasas Receptoras , Receptores de Factores de Crecimiento de Fibroblastos/análisis , Adolescente , Adulto , Anciano , Femenino , Factor 1 de Crecimiento de Fibroblastos/inmunología , Glomerulonefritis/metabolismo , Rechazo de Injerto/complicaciones , Rechazo de Injerto/inmunología , Humanos , Hibridación in Situ , Riñón/química , Riñón/patología , Riñón/ultraestructura , Glomérulos Renales/química , Glomérulos Renales/citología , Masculino , Persona de Mediana Edad , Nefrectomía , ARN Mensajero/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/inmunología , Valores de Referencia , Estudios Retrospectivos

RESUMEN

Advances in systemic immunosuppressive therapy for solid organ transplantation have done little to decrease the percentage of allografts that eventually will develop chronic rejection. However, one of the promises of modern molecular biology includes the ability to introduce new genetic information into mammalian hosts. The ability to deliver genes and control their expression in the adult kidney has been described in appropriate animal models. Consequently, gene transfer technology represents a realistic therapeutic approach to modify the allogeneic kidney before engraftment in an effort to decrease the incidence of posttransplant dysfunction. To bridge the gap between animal studies and the clinical application of this technology, we report the first genetic transfection of isolated human kidneys under conditions of organ preservation. Polymerase chain reaction, reversed transcription polymerase chain reaction, and in situ hybridization techniques demonstrated that an adenovirus-polylysine-deoxyribonucleic acid (DNA) complex can be used to insert a complementary DNA expression vector encoding beta-galactosidase into the intact human kidney. Immunohistochemical and in situ enzymatic analyses determined further that gene delivery and expression were localized in proximal tubular epithelial cells. Consequently, targeting of genes to perturb mediators of the local inflammatory response may represent a rational therapeutic interventional strategy in chronic rejection of the kidney.

Asunto(s)

Técnicas de Transferencia de Gen , Trasplante de Riñón , Riñón/metabolismo , Adenoviridae/genética , Adulto , Secuencia de Bases , Femenino , Vectores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , beta-Galactosidasa/genética

RESUMEN

OBJECTIVE: To determine the efficacy and relative effectiveness of conjugated entrogens (CE) and fresh-frozen plasma (FFP) in normalizing prolonged preoperative bleeding times during renal transplantation. DESIGN: Prospective, randomized trial. SETTING: A university regional referral center for transplantation. PATIENTS: Patients scheduled for renal transplantation with preoperative bleeding times greater than 10 minutes (normal, < 7 minutes) following informed consent were asked to participate in the randomized protocol. Those with bleeding times of 8 to 9.5 minutes were asked, following informed consent, to be a control group receiving neither CE nor FFP. INTERVENTIONS: Following induction of anesthesia and drawing of baseline laboratory tests, patients were administered randomly, using a table of random numbers, either 50 mg of CE or 2 U of FFP. MAIN OUTCOME MEASURES: Bleeding time measurements and other laboratory tests were repeated at the end of surgery as well as at 24 and 48 hours postoperatively. RESULTS: Treatment with CE and FFP decreased the patients' bleeding times from 16.68 +/- 0.8 (SEM) and 17.13 +/- 0.85 minutes to 7.67 +/- 0.79 (P < .001) and 10.50 +/- 1.27 minutes (P < .001), respectively, by the end of surgery. At 24 and 48 hours postoperatively, the CE group had bleeding times of 9.77 +/- 0.99 and 9.81 +/- 1.24 minutes (P < .001 for both), respectively, whereas the FFP group bleeding times were 12.76 +/- 1.57 (P = .003) and 12.14 +/- 1.56 minutes (P = .001), respectively. There were no statistical differences for the control group compared with baseline either at the end of surgery or at 24 hours. CONCLUSIONS: Although both CE and FFP significantly decreased prolonged preoperative bleeding times during renal transplantation, CE might be preferred because of lower risk and cost, as well as a longer duration of action.

Asunto(s)

Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/terapia , Coagulantes/uso terapéutico , Estrógenos Conjugados (USP)/uso terapéutico , Trasplante de Riñón , Plasma , Adulto , Pruebas de Coagulación Sanguínea , Transfusión Sanguínea , Coagulantes/administración & dosificación , Coagulantes/economía , Costos de los Medicamentos , Estrógenos Conjugados (USP)/administración & dosificación , Estrógenos Conjugados (USP)/economía , Humanos , Consentimiento Informado , Cuidados Posoperatorios , Cuidados Preoperatorios , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Interest in nonimmunologic factors affecting longterm graft survival has focused on adequacy of nephron dosing. Body surface are (BSA) is a reliable surrogate for nephron mass. In a retrospective study of 378 primary recipients of paired kidneys from 189 cadaveric donors, we assessed the impact of matching donor and recipient BSA on outcome over 7 years. BSA of donors was 1.82 +/- 0.26 m2. Initially, paired recipients of kidneys from a single donor were divided into two groups. Group 1 included the recipient with the larger BSA of the pair (1.97 +/- 0.17 m2), while group 2 consisted of smaller BSA recipients (1.69 +/- 0.19 m2). Although early function was better in group 2 patients, graft survival at 1 year (77% vs. 79%) and 5 years (54% vs. 55%) was identical between groups, as were most recent serum creatinine levels (2.0 +/- 0.1 vs. 2.1 +/- 0.1 mg/dl). A second analysis divided patients with a functioning allograft at discharge from initial transplant hospitalization (n = 345) into three groups based solely on donor to recipient BSA ratio: the ratio of group A (n = 30) was < or = 0.8, that of group B (n = 255) was between 0.81 and 1.19, and that of group C (n = 51) was > or = 1.2. Graft survival and kidney function over 5 years did not differ among groups. In multivariate analysis of 17 variables, donor:recipient BSA, independent of other risk factors, did not affect risk allograft loss. These data indicate that including nephron mass as a criterion for cadaveric organ allocation is unlikely to improve long-term results in renal transplantation.

Asunto(s)

Trasplante de Riñón/métodos , Adulto , Superficie Corporal , Cadáver , Creatinina/sangre , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Riñón/patología , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos

RESUMEN

Removal of a failed primary renal allograft was found by some groups to adversely affect the outcome of a second kidney transplant. Recent data does not support this view and fail to show any such effect. Such data, however, are limited by small numbers or univariate analysis. The records of 192 patients receiving a primary and a subsequent kidney transplant between January 1980 and July 1992 were retrospectively reviewed. Immunosuppression initially included azathioprine and prednisone; cyclosporine was introduced in December 1983 with Minnesota antilymphocyte globulin (MALG) added for induction in May 1987. Regraft survival rates were 66% at one year and 60% at two years. Using Kaplan-Meier survival analysis patients having primary transplant nephrectomy had a worse second allograft outcome than patients who kept their failed grafts (P = 0.0003). Multivariate analysis showed a significant relationship between primary allograft survival and retransplant outcome. To eliminate this influence, patients whose first graft failed within six months of transplantation were excluded from the analysis. This resulted in 90 patients whose first graft functioned for more than 6 months. Graft survival was 80% at one year and 73% at 2 years in this select population. Patients with prior transplant nephrectomy still had a worse retransplant outcome than those who kept their failed grafts (P = 0.05). Multivariate analysis identified primary allograft nephrectomy, older donor age, longer interval from nephrectomy to retransplant, and lack of MALG at induction as negative risk factors. In conclusion, primary allograft nephrectomy may have a negative influence on second renal transplant outcome. This result may be improved by reducing donor age and the time interval from nephrectomy to retransplantation, and using MALG at induction.

Asunto(s)

Trasplante de Riñón , Nefrectomía , Adulto , Suero Antilinfocítico/uso terapéutico , Femenino , Supervivencia de Injerto , Humanos , Masculino , Reoperación , Factores de Riesgo , Trasplante Homólogo

RESUMEN

OBJECTIVE: The study analyzed 3359 consecutive renal transplant operations for patient and graft survival, including living related, cadaveric, and living unrelated patients. The analysis was separated into three groups according to immunosuppression and date of transplant. SUMMARY BACKGROUND DATA: Improvements in renal transplantation in the past 25 years have been the result of better immunosuppression, organ preservation, and patient selection. METHODS: A single transplant center's experience over a 25-year period was analyzed regarding patient and graft survival. Potential risk factors included patient demographics, tissue typing, donor characteristics, number of transplants, acute and chronic rejection, acute tubular necrosis, primary disease, and malignancy. RESULTS: The primary cause of graft loss was rejection. Improvement in cadaveric graft survival since 1987 with quadruple therapy was not apparent in living donor patients. Race continued to be a negative factor in graft survival. Avoiding previous mismatched antigens and the use of flow cytometry improved allograft survival. The leading cause of death in the past 7 years in cadaveric recipients was cardiac (52%). CONCLUSIONS: Improved graft survival in the past 25 years was related to 1) advances in immunosuppression, 2) better methods of cytotoxic antibody detection, and 3) human lymphocyte antigen match.

Asunto(s)

Fallo Renal Crónico/cirugía , Trasplante de Riñón/inmunología , Inmunología del Trasplante , Adolescente , Adulto , Anciano , Cadáver , Niño , Preescolar , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Lactante , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo