RESUMEN
PURPOSE: Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemodialysis access they do have significant problems due to initial non-maturation and a later venous stenosis. These problems appear to have been exacerbated following a push to increase AVF prevalence in the US. The reasons for both AVF non-maturation and the later venous stenoses are unclear but are thought to be related to abnormal hemodynamic wall shear stress (WSS) profiles. This technical note aims to describe the successful development of measurement techniques that can be used to establish a complete hemodynamic profile in a pig model with two different configurations of AVF. METHODS AND RESULTS: The curved and straight AVF configurations were created in an in vivo pig model. Flow and pressure in the AVFs were measured using the perivascular flow probes and Doppler flow wires while the pressure was recorded using a pressure transducer. The anatomical configuration was obtained using two different approaches: a) combination of intravascular ultrasound (IVUS) and angiograms, (b) 64 slice CT angiography. 3D models were reconstructed using image processing and computer modeling techniques. Numerical calculations were then performed by applying the measured flow and pressure data into the configurations to obtain the hemodynamic WSS profiles. CONCLUSION: The described methodologies will allow the calculation and optimization of WSS profiles in animal models. This information could then be translated to the clinical setting where it would have a positive impact on improving the early maturation rates of AVFs as well as reducing the late venous stenoses.
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Derivación Arteriovenosa Quirúrgica/normas , Velocidad del Flujo Sanguíneo/fisiología , Arteria Femoral/anatomía & histología , Arteria Femoral/fisiología , Vena Femoral/anatomía & histología , Vena Femoral/fisiología , Diálisis Renal/métodos , Angiografía/métodos , Animales , Simulación por Computador , Modelos Animales de Enfermedad , Endosonografía/métodos , Porcinos , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler/métodosRESUMEN
UNLABELLED: Early corticosteroid withdrawal has recently been shown to be possible in recipients of simultaneous pancreas kidney transplants; however, its feasibility in solitary pancreas recipients has not been documented. In the present study, we provide evidence that early withdrawal can be achieved in pancreas as well as pancreas-kidney recipients. METHODS: Twenty type I diabetics underwent 13 pancreas-kidney transplants and 7 pancreas-only transplants with early withdrawal (methylprednisone 6-day taper). Additional immunosuppression consisted of tacrolimus, mycophenolate mofetil, and thymoglobulin induction (five doses). RESULTS: Transplants included 13 pancreas-kidney, 6 pancreas after kidney transplant, and 1 pancreas after islet transplant. Overall mean follow-up was 7.3 months. One episode of pancreas transplant rejection after pancreas-only transplant was detected on protocol biopsy without biochemical abnormalities. One renal allograft rejection occurred 65 days posttransplant in a pancreas-kidney recipient and was graded as a Banff IA rejection. A single pancreas graft loss occurred due to thrombosis 6 days after pancreas-kidney transplantation. CONCLUSIONS: These results indicate that relatively short thymoglobulin induction (five doses) with tacrolimus and mycophenolate mofetil can allow early withdrawal in both pancreas-kidney and pancreas-only transplant recipients.
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Corticoesteroides/administración & dosificación , Diabetes Mellitus Tipo 1/cirugía , Trasplante de Páncreas/fisiología , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Nefropatías Diabéticas/inmunología , Nefropatías Diabéticas/cirugía , Esquema de Medicación , Femenino , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/fisiología , Masculino , Ohio , Trasplante de Páncreas/inmunología , Proyectos Piloto , Grupos RacialesRESUMEN
INTRODUCTION: The purpose of this study was to determine whether incidentally discovered, small renal cell cancers (RCC) in donor kidneys can be excised and safely transplanted. METHODS: The Israel Penn International Transplant Tumor Registry database was searched and all small RCC that were identified and resected prior to transplantation of deceased and living donor kidneys were reviewed. Patient demographics, tumor characteristics, recurrence, and survival were examined. RESULTS: Fourteen kidneys were identified in which small RCC were noted at the time of procurement and where the tumors were excised ex vivo and then transplanted. Eleven kidneys were obtained from living related donors and three were from deceased donors. Median tumor size was 2 cm (range 0.5 to 4 cm). All 14 tumors were of histological Furhman grade II/VI (n = 8) or Furhman grade I/VI (n = 6). All kidneys had pathologically confirmed negative margins. The mean age of the recipients was 40.8 +/- 9.2 years, with the majority being men (11 men; 3 women). Median follow-up for this group was 69 months (range 14 to 200 months). There have been no recurrences of tumor in these recipients and the 1-, 3-, and 5-year patient and graft survivals are 100%, 100%, and 93%. CONCLUSIONS: These data represent the only data available (to our knowledge) on this issue. This experience indicates that donor kidneys with small, incidental RCC and low histological grade (Furhman grade I and II/IV) can be managed with excision and transplantation, with a low risk of tumor recurrence in the recipient.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Trasplante de Riñón/fisiología , Donantes de Tejidos/estadística & datos numéricos , Humanos , Selección de Paciente , Sistema de Registros , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
UNLABELLED: Experience with early corticosteroid withdrawal (CSWD) in renal transplant recipients with focal segmental glomerulosclerosis (FSGS) has not been previously reported. Since corticosteroids are used to treat primary FSGS, concern exists as to whether early CSWD regimens will be associated with an increased risk of FSGS recurrence posttransplant. The purpose of the present study was to evaluate the results of early CSWD in FSGS recipients and compare these results to a historic control group of FSGS patients who underwent renal transplantation under corticosteroid-based immunosuppression. METHODS: Forty-three patients with FSGS underwent renal transplantation with early CSWD. Results in these patients were compared to FSGS patients that underwent renal transplantation with chronic corticosteroid therapy. All rejection episodes were biopsy proven with grading by Banff criteria. Statistical analyses included Student's t test and chi square tests. RESULTS: Results in 43 patients with a median follow-up of 569 days were analyzed and compared to control patients. There was no significant difference in recurrent FSGS, time to recurrence, or graft loss. CONCLUSION: CSWD does not increase risk for recurrence of FSGS. These observations indicate that ECSW can be achieved in FSGS patients, thereby affording them the benefits of steroid elimination.
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Corticoesteroides/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/patología , Trasplante de Riñón/patología , Corticoesteroides/administración & dosificación , Adulto , Creatinina/sangre , Esquema de Medicación , Estudios de Seguimiento , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Humanos , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
BACKGROUND: The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein. METHODS: Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria. RESULTS: Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1). CONCLUSIONS: This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.
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Corticoesteroides/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Corticoesteroides/administración & dosificación , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Rechazo de Injerto/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Proyectos Piloto , Estudios ProspectivosRESUMEN
African Americans have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. Modern immunosuppression has reduced rejections and improved graft survival in African Americans and may allow successful corticosteroid withdrawal. Outcomes in 56 African Americans were compared to 56 non-African Americans enrolled in early withdrawal protocols. Results are reported as African American versus non-African American. Acute rejection at 1 year was 23% and 18% (P = NS), while patient and graft survival was 96% versus 98% and 91% versus 91% (P = NS), respectively. In conclusion, early withdrawal in African Americans is associated with acceptable rejection rates and excellent patient and graft survival, indicating that the risks and benefits of early withdrawal are similar between African Americans and non-African Americans. Additional followup is needed to determine long-term renal function, graft survival, and cardiovascular risk in African Americans with early steroid withdrawal.
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Corticoesteroides/uso terapéutico , Negro o Afroamericano , Supervivencia de Injerto/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/fisiología , Corticoesteroides/administración & dosificación , Suero Antilinfocítico/uso terapéutico , Esquema de Medicación , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Análisis de Supervivencia , Factores de TiempoRESUMEN
Dietary supplementation with fatty acids was carried out to examine whether the type and timing of dietary manipulation would have an effect on transfusion-induced immunosuppression in a rat cardiac transplant model. Linoleic acid (LA), oleic acid (OA), and fish oil (FO) were used because of their different effects on arachidonic acid (AA) metabolism. Pretransplant inhibition of AA metabolism (OA) shortened graft survival when compared with water-fed controls. Posttransplant LA (AA precursor) significantly prolonged graft survival. Pre- and posttransplant supplementation of LA and OA resulted in even more prolongation and shortening of graft survival, respectively. These findings suggest that transfusion-induced immunosuppression is partially mediated by AA metabolites, which are necessary for the pretransplant induction and posttransplant maintenance of the suppressed state. Dietary immunoregulation of transfusion induced immunosuppression is possible. The timing of dietary intervention and type of lipid supplementation is important in regulation of the immune response.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Dieta , Terapia de Inmunosupresión , Animales , Transfusión Sanguínea , Supervivencia de Injerto , Tolerancia Inmunológica , Ácido Linoleico , Ácidos Linoleicos/administración & dosificación , Masculino , Ratas , Ratas Endogámicas BUF , Ratas Endogámicas Lew , Factores de Tiempo , Trasplante HomólogoRESUMEN
Increased prostaglandin production is a possible mechanism for the immunosuppressive effects of both cyclosporine and blood transfusions. Therefore, dietary supplementation with linoleic acid, a prostaglandin precursor, combined with either modality could act synergistically. Intraabdominal cardiac allografts were performed from Buffalo rat donors to Lewis recipients. Transplant recipients received a single donor-specific transfusion, low-dose cyclosporine (CsA, 1 mg/kd/d x 7 days), dietary supplementation with linoleic acid (LA, 16% of total calories) or a combination of the three modalities. CsA, DST or LA alone significantly prolonged allograft survival. Both CsA and LA acted synergistically with DST in further prolongation of survival--however, animals receiving all three modalities achieved 100% long-term survival. Augmentation of transfusion- and cyclosporine-induced immunosuppression with dietary prostaglandin precursor is possible.
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Transfusión Sanguínea , Ciclosporinas/uso terapéutico , Grasas de la Dieta/uso terapéutico , Refuerzo Inmunológico de Injertos , Ácidos Linoleicos/uso terapéutico , Donantes de Tejidos , Animales , Terapia Combinada , Sinergismo Farmacológico , Quimioterapia Combinada , Refuerzo Inmunológico de Injertos/métodos , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón , Ácido Linoleico , Masculino , Ratas , Ratas Endogámicas BUF , Ratas Endogámicas LewRESUMEN
Exocrine secretions of 16 of 22 pancreas allografts were drained into the urinary tract. Seven of these 16 patients have functioning allografts, six with pancreaticocystostomies and one with duct-to-ureter anastomosis. A notable problem has been a chronic metabolic acidosis, along with weight loss and hypotension, secondary to chronic bicarbonate loss and volume depletion through the urinary pancreatic fistula. This occurred as early as one week posttransplant, and intermittently thereafter up to four years. The syndrome was aggravated by episodes of renal dysfunction (acute tubular necrosis or rejection), and febrile syndromes. An inverse relationship between serum and urine bicarbonate concentrations existed, with a correlation coefficient, r = -0.746, (P less than 0.05). A negative correlation was also noted between serum bicarbonate and serum creatinine, r = 0.726, (P less than 0.05). Hyperchloremic metabolic acidosis with normal anion gap occurred despite periods of marginal pancreas allograft function resulting from ongoing rejection. Treatment consisted of intravenous and/or oral bicarbonate supplementation, and bicarbonate dialysis for uremic patients. In addition, one patient was first seen with severe balanitis and urethritis due to documented activation of trypsinogen and chymotrypsinogen, presumably caused by recurrent episodes of urinary tract infection. Urinary assay revealed a 10(2-3) increase in activated trypsin and chymotrypsin in comparison with other asymptomatic allograft recipients. Conversion to ductal enteric drainage led to resolution of both the balanitis and bicarbonate wasting. Measurement of urinary amylase levels were gross indicators of graft viability since no correlation could be found between these levels, onset of hyperglycemia, and eventual graft rejection confirmed by pathological examination.
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Trasplante de Páncreas , Sistema Urinario/cirugía , Acidosis/fisiopatología , Adulto , Amilasas/orina , Bicarbonatos/metabolismo , Glucemia/metabolismo , Quimotripsina/orina , Creatinina/sangre , Activación Enzimática , Femenino , Supervivencia de Injerto , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Páncreas/fisiología , Jugo Pancreático/fisiología , Tripsina/orina , Sistema Urinario/patología , Sistema Urinario/fisiopatologíaRESUMEN
A rat heart allograft model employing donor-specific transfusions (DSTs) was used to investigate several questions relevant to their clinical usage. The effects of varying blood storage duration (stored vs. fresh), number and timing of DSTs as well as use of concomitant azathioprine and cyclosporine (CsA) were assessed in terms of allograft survival and recipient sensitization. A comparison of stored and fresh-blood DSTs revealed that blood stored for up to 5 weeks was as effective as fresh blood and that a 2-week storage was optimal. Increased storage appeared to be associated with decreased sensitization. Multiple DSTs were more effective than a single DST and the peak effect appeared after six. Transfusions given at the time of transplantation were ineffective. The addition of concomitant (preoperative) azathioprine or CsA resulted in a further decrease in sensitization but also resulted in a dose-dependent diminution of the transfusion effect.
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Transfusión Sanguínea , Trasplante de Corazón , Animales , Azatioprina/uso terapéutico , Ciclosporinas/uso terapéutico , Supervivencia de Injerto/efectos de los fármacos , Masculino , Preservación de Órganos , Ratas , Ratas EndogámicasRESUMEN
This study details 11 pancreas transplant recipients (10 combined kidney and pancreas and 1 pancreas after kidney) who were converted to tacrolimus (FK506) due to acute severe cyclosporine nephrotoxicity in 8 cases and persistent rejection with cyclosporine toxicity in three cases. Arteriolopathy was documented by renal histology in all cases. Cyclosporine was discontinued for 24 hr immediately prior to initiation of tacrolimus. Tacrolimus was started orally at 0.1 mg/kg twice daily with dose adjustments to maintain whole blood trough levels of 8-15 ng/mL by IMx. Tacrolimus was initiated a mean of 14.5 months (range 1-81) after pancreas transplantation. The mean serum creatinine level had increased to 2.9 mg/dl from 1.0 mg/dl at the diagnosis of cyclosporine arteriolopathy (P=0.003). The mean serum creatinine and blood glucose levels at the time of initiation of tacrolimus were 2.1 mg/dl and 104 mg/dl, respectively. Serum creatinine was 1.7 mg/dl, 1.9 mg/dl, 1.8 mg/dl, and 1.7 mg/dl after 1, 2, 3, and 6 months of tacrolimus therapy, respectively; ANOVA (P = 0.02). The corresponding blood glucose levels were 117 mg/dl, 112 mg/dl, 109 mg/dl, and 116 mg/dl, respectively (P=NS). Normal C-peptide levels were present before (5.9 ng/ml) and after (6.2 ng/ml), the initiation of tacrolimus therapy (P=NS), and mean HbA1C was 6.1% before and 6.3% after tacrolimus therapy, (P=NS). There were 4 episodes of acute rejection, 3 responded to intravenous methylprednisolone, and 1 required OKT3 during tacrolimus therapy. Reversible tacrolimus nephrotoxicity was noted in three patients without any evidence of progressive vasculopathy. All 11 patients are alive, and 10/11 kidney and pancreas grafts are functioning with a mean follow-up of 7.7 months (range 5-10). In this study, conversion from cyclosporine to tacrolimus in kidney and pancreas recipients resulted in improvement and stabilization of renal function while maintaining stable blood glucose, C peptide, and HbA1C levels.
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Ciclosporina/toxicidad , Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Riñón/patología , Trasplante de Páncreas , Tacrolimus/administración & dosificación , Administración Oral , Adulto , Femenino , Humanos , Inmunosupresores/toxicidad , Masculino , Persona de Mediana EdadRESUMEN
A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. Twenty-one patients had received kidneys from living-related donors, the remaining 56 from cadaveric donors. The cause of proteinuria in these 77 patients was as follows: transplant glomerulopathy (30), allograft glomerulonephritis (22), chronic rejection (21), renal vein thrombosis (2), diabetic glomerulosclerosis (1), and hypertensive nephrosclerosis (1). Of the 22 patients who developed glomerulonephritis in the transplanted kidney, 6 had recurrent disease (3--membranous glomerulopathy, 2--focal sclerosis and hyalinosis, 1--membranoproliferative glomerulonephritis); 6 developed de novo glomerulonephritis; and in 10 the type of glomerulonephritis could not be classified as recurrent or as de novo because of lack of characterization of the original kidney disease. Renal vein thrombosis occurred in association with other lesions in an additional 5 cases (3--chronic rejection; 2--membranous glomerulopathy). In follow-up only 23.4% (18 of 77) of the patients maintained prolonged graft function; the majority of grafts being lost within one year of the development of persistent, heavy proteinuria. Of the 18 patients who retained their grafts, 8 had glomerulonephritis, 5 transplant glomerulopathy, and 5 chronic rejection. This study confirms the poor prognosis that has been reported with the development of nephrotic-range proteinuria in renal allograft recipients.
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Trasplante de Riñón , Proteinuria/etiología , Supervivencia de Injerto , Humanos , Riñón/patología , Pronóstico , Proteinuria/patologíaRESUMEN
Kidney and patient survival of 351 consecutive patients undergoing first cadaveric renal transplants since 1968 were reviewed to determine the effects of splenectomy on outcome. Special emphasis was given to analysis of 106 splenectomized and 102 nonsplenectomized patients treated since 1975. During the first two years after transplant, kidney survival was better in the splenectomized patients, with no adverse effect on patient survival. However, after the first two years, patient survival became significantly worse in splenectomized patients (35.5% vs. 60.5% at 84 months). Of the deaths, infection was the cause in 26.7% of nonsplenectomized patients compared with 50% of splenectomized patients (P less than 0.07). Of patients alive at one year posttransplant, death rates were not different in patients splenectomized before 1975 or after 1975. Timing of splenectomy (prior vs. concurrent) had no effect on outcome. The adverse effect of splenectomy on mortality appeared to be more pronounced in younger (less than or equal to 45 year-old) than in older (greater than 45 year-old) patients. Splenectomy should not be performed routinely in preparation for a cadaveric transplant because of an unacceptably high late mortality that is primarily from sepsis.
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Trasplante de Riñón , Esplenectomía/efectos adversos , Adulto , Factores de Edad , Anciano , Infecciones Bacterianas/mortalidad , Supervivencia de Injerto , Humanos , Persona de Mediana Edad , Pronóstico , Factores de TiempoRESUMEN
OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)
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Anticuerpos Antiidiotipos/biosíntesis , Anticuerpos Monoclonales/uso terapéutico , Inmunoglobulina G/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Ciclosporinas/farmacología , Humanos , Terapia de Inmunosupresión , RatonesRESUMEN
OKT3 is a murine monoclonal antibody to the CD3 antigen of human T lymphocytes. The production of human antimurine antibodies after treatment with OKT3 has been perceived as a major limitation to its extended use and reuse. Treatment of 142 patients with 168 courses of OKT3 resulted in the development of antimouse antibody in 28% of the patients. Twenty-six patients (16 kidney, 6 liver, 3 heart, 1 pancreas) have been retreated with 27 courses of OKT3. Eighteen patients had no antimurine antibodies present, and the rejection reversal rate was 83% (15/18). Six patients had a low-titer antimurine antibody present, and rejection reversal occurred in 5 (83%). Rejection was not reversed in 2 patients with a high-titer antibody. Development of antimurine antibody was more frequent in renal transplant recipients (33%) than in hepatic (12%) or cardiac transplant recipients (18%). We believe that this reflects the fact that concomitant immunosuppressive therapy is more likely to be reduced during OKT3 therapy in renal transplant recipients than in hepatic or cardiac transplant recipients. Retreatment of patients with no anti-OKT3 antibody resulted in depletion of CD3+ cells from the peripheral blood, but it took longer than in patients being treated with OKT3 for the first time. Similarly, serum OKT3 levels rose more slowly in retreated patients compared to first treatment. In retreating patients with a low-titer antimurine antibody, it often was necessary to increase the dose of OKT3 in order to achieve adequate serum OKT3 levels and to deplete CD3+ cells. De novo antimurine antibody developed in 4 of the 18 (22%) antibody-negative patients who were retreated. In conclusion, retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low-titer antibodies does not preclude successful retreatment with OKT3; however, alternate antirejection therapy should be used in patients with high-titer antimurine responses.
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Anticuerpos Antiidiotipos/biosíntesis , Anticuerpos Monoclonales/uso terapéutico , Antígenos de Diferenciación de Linfocitos T/inmunología , Rechazo de Injerto , Receptores de Antígenos de Linfocitos T/inmunología , Anticuerpos Monoclonales/inmunología , Antígenos de Diferenciación de Linfocitos T/análisis , Complejo CD3 , Humanos , Terapia de Inmunosupresión/métodos , Trasplante de Riñón , Trasplante de Hígado , Linfocitos/clasificación , Linfocitos/inmunología , Factores de TiempoRESUMEN
A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.
Asunto(s)
Transfusión Sanguínea , Ciclosporina/uso terapéutico , Trasplante de Riñón/inmunología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Adulto , Cadáver , Relación Dosis-Respuesta a Droga , Epítopos , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Hepatitis/prevención & control , Humanos , Inmunidad/efectos de los fármacos , Inmunosupresores/administración & dosificación , Trasplante de Riñón/mortalidad , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Donantes de TejidosRESUMEN
Thallium-201 was used to image a patient with a pancreatic transplant. Incomplete visualization of the graft on the 201Tl scan, compared to CT, led to the diagnosis of segmental necrosis of the tail of the graft. Due to the low background and favorable target-to-non-target ratio, 201Tl pancreas scintigraphy may be useful in the follow-up of pancreatic transplants.
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Trasplante de Páncreas/patología , Páncreas/diagnóstico por imagen , Adulto , Humanos , Masculino , Necrosis , Páncreas/patología , Cintigrafía , Pentetato de Tecnecio Tc 99m , Radioisótopos de TalioRESUMEN
UNLABELLED: The purpose of this study was to evaluate the feasibility of using 99mTc-sestamibi in the assessment of pancreatic transplant. METHODS: Ten transplant recipients with a history of insulin-dependent diabetes mellitus were studied. Fourteen 99mTc-sestamibi studies were performed. Each patient was injected intravenously with 10 mCi of 99mTc-sestamibi. Two-second frames were obtained for 1 min, followed by serial dynamic and static images every 5 min for 30 min. Technetium-99m sestamibi studies, read by two nuclear medicine physicians, were correlated with clinicopathologic findings and compared to the ten 201Tl studies obtained in seven of these patients. RESULTS: On 99mTc-sestamibi images, normally functioning grafts showed adequate perfusion on the angiogram and good uptake followed by clearance on static images. Time-activity curves showed an initial upslope followed by a downslope after the initial uptake peak. The quality of 99mTc-sestamibi images was superior to those of 201Tl in five, similar in four and marginally inferior in one paired study. Technetium-99m-sestamibi was used for both flow and static images, whereas a 99mTc radiotracer angiogram was needed to accompany the 201Tl study. CONCLUSION: Our preliminary experience indicates that 99mTc-sestamibi helps evaluate pancreatic transplants and provides high count statistics, which result in better image quality and diagnostic detail. Extensive quantitative studies are being performed to further evaluate this agent's role in the clinical management of pancreatic transplant patients.
Asunto(s)
Trasplante de Páncreas , Páncreas/diagnóstico por imagen , Tecnecio Tc 99m Sestamibi , Adulto , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Diabetes Mellitus Tipo 1/cirugía , Femenino , Rechazo de Injerto/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/efectos adversos , Cintigrafía , Radioisótopos de TalioRESUMEN
Atheroembolic disease is a known cause of renal failure following invasive vascular procedures in patients with atherosclerosis. It is, however, not generally associated with renal transplant dysfunction. We report on a case of donor-transmitted atheroembolic renal disease, which led to an immediate loss of the transplant kidney in the operating room. Risk factors associated with this condition and methods to prevent this complication are discussed.
Asunto(s)
Enfermedades Renales/patología , Trasplante de Riñón/patología , Riñón/patología , Tromboembolia/patología , Cadáver , Femenino , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Fallo Renal Crónico/cirugía , Persona de Mediana Edad , Donantes de Tejidos , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
A case of synchronous kidney and pancreas transplantation in which a whole pancreas graft had been drained to the urinary bladder is discussed. On the 137th postoperative day, the patient presented with symptomatic balanitis and urethritis. Documented enzymatic activation of the trypsinogen/chymotrypsinogen, which is not present in symptom-free control patients, was thus thought to be responsible for these symptoms. Conversion to enteric drainage by means of a Roux-en-Y loop resulted in resolution of both symptoms and urinary enzymatic activation. Recurrent urinary tract infections were thought to be the most likely mechanism responsible for these findings.