RESUMEN
INTRODUCTION: Basiliximab is a monoclonal antibody directed to the interleukin-2 receptor. Several studies have demonstrated both its efficacy and safety. Even with the use of polyclonal antibodies in renal pediatric transplant recipients, the local incidence of steroid-resistant rejections has been close to 10% of the total incidence of acute rejection episodes (AREs). An open, multicenter prospective study was performed to assess the safety tolerability, and efficacy of induction with basiliximab in renal pediatric transplant patients receiving cyclosporine, mycophenolate, and steroids. MATERIALS AND METHODS: Eighteen patients (8 boys) of mean age 11.9 +/- 4.5 years and body weight 32 +/- 15 kg received cadaveric (n = 7) or living (n = 11) donor grafts. Simulect was administered on days 0 and 4. Efficacy was assessed by the incidence of biopsy-proven acute rejection (BPAR). Safety assessment consisted of a description of the adverse events (AEs). RESULTS: Six BPAR (Banff I and II) occurred in 5, (27.7%) children all of which were steroid responsive. Creatinine levels at day 7 and months 3, 6, and 12 were 1.6 +/- 1.5 mg/dL, 1.0 +/- 0.4 mg/dL, 1.0 +/- 0.5 mg/dL, and 1.0 +/- 0.4 mg/dL, respectively. Schwartz calculation at 12 months was 71 +/- 15 mL/1.73 m2 AEs were hypertension (12), anemia (9), abdominal pain (8), metabolic acidosis (8), nausea (7), diarrhea (2), gingival hypertrophy (2), hirsutism (2), lymphocele (2), and infections (15). No deaths, graft losses, PTLDs, or malignancies were observed. CONCLUSIONS: No steroid-resistant AREs, were observed in this pediatric group using basiliximab. The Schwartz calculation at 12 months was 71 +/- 15 mL/min/1.73 m2.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Rechazo de Injerto/patología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Corticoesteroides/uso terapéutico , Basiliximab , Biopsia , Cadáver , Niño , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Prueba de Histocompatibilidad , Humanos , Donadores Vivos , Masculino , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Seguridad , Donantes de TejidosRESUMEN
Transforming growth factor (TGF)-beta1 is important in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy (CAN). The angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopressor angiotensin II. Angiotensin II is also a growth factor and a profibrogenic cytokine. It mediates the induction of TGF-beta1. We studied the relationship among the intragraft expression of AGT, TGF-beta1, and CAN in stable renal transplant patients (RTP). We used a competitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)-ELISA assay to identify intragraft amounts of AGT expression in RTP and correlated it with TGF-beta1 mRNA expression. We studied and performed kidney biopsies on 12 RTP with long-functioning grafts and 6 RTP in the immediate posttransplantation period (7 days) who had acute tubular necrosis as control. Histology was based on Banff working classification criteria. Total RNA was isolated from biopsy specimens. For RT-PCR-ELISA, we created heterologous RNA competitors that coamplified with the same primers as AGT and TGF-beta1. Six of 12 long RTP had proteinuria >1000 mg/24 hr and 6 had proteinuria <1000 mg/24 hr. The differences between Banff grades (P =0.03), AGT, and TGF-beta1 levels by RT-PCR-ELISA were statistically significant between both groups (106.2+/-60.7 vs. 34.1+/-11.9 pg/microg total RNA [P =0.01] and 5954+/-5612 vs. 436+/-517 transcripts/microg total RNA [P =0.01], respectively). The control group showed AGT levels of 25+/-12.2 pg/microg total RNA and TGF-beta1 levels of 228+/-111 transcripts/microg total RNA, significant only for the higher proteinuria group (P=0.01 and P=0.04, respectively). There was a correlation between AGT and TGF-beta1 in both groups (r=0.96, P=0.001). We showed a relationship between mRNA expression of AGT and TGF-beta1 in kidney transplant patients with different grades of CAN and proteinuria.
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Angiotensinógeno/genética , Trasplante de Riñón/fisiología , ARN Mensajero/genética , Transcripción Genética , Factor de Crecimiento Transformador beta/genética , Adulto , Cadáver , Enfermedad Crónica , Ciclosporina/uso terapéutico , Femenino , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/patología , Donadores Vivos , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Trasplante HomólogoRESUMEN
BACKGROUND: Host immunity plays an important role in the development of human papillomavirus (HPV)-associated disease. The HPV infection in oral cyclosporin-induced gingival overgrowth in renal transplant recipients has not been investigated previously. The aim of this study was to establish the HPV infection of cyclosporin-induced gingival hyperplasia in renal transplant recipients through morphological changes and use of the in situ hybridization technique. METHODS: We examined 13 renal transplant recipient biopsies with gingival overgrowth lesions and 4 healthy mucosa samples of these patients. The histopathological diagnoses were established on the basis of widely accepted criteria, and the pathologist was not aware of the HPV result. An in situ molecular hybridization was carried out under low stringent conditions to detect HPV species with mixed biotin-labeled probes of HPV 6 and HPV 11, and under high stringent conditions with HPV 6, HPV 11, HPV 16, and HPV 18 probes for HPV typing. RESULTS: The HPV prevalence among the 13 samples studied was 92.31% (12/13), of which 4 tested positive for HPV 6-11 and 1 for HPV 16. The 4 biopsies of normal mucosa from gingival overgrowth patients were also reactive for HPV DNA. In 11/12 (91.7%) HPV-positive cases, koilocytotic atypia was found. CONCLUSIONS: The suppression of T-cell function by cyclosporin therapy can result in an increase of HPV infection, adding to the proliferative activity of cyclosporin in the oral mucosa.
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Ciclosporina/efectos adversos , Sobrecrecimiento Gingival/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón , Papillomaviridae , Infecciones por Papillomavirus/clasificación , Infecciones Tumorales por Virus/clasificación , Adolescente , Adulto , Núcleo Celular/ultraestructura , Colorantes , Citoplasma/ultraestructura , ADN Viral/análisis , Femenino , Encía/patología , Encía/virología , Sobrecrecimiento Gingival/patología , Sobrecrecimiento Gingival/virología , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Mucosa Bucal/virología , Papillomaviridae/clasificación , Papillomaviridae/genética , Trasplante Homólogo , Vacuolas/ultraestructuraRESUMEN
The aim of this study was to report on the occurrence of conventional and emerging viral agents as well as their etiological link with diarrhea in kidney transplanted subjects from Cordoba, Argentina. A total of 42 stool samples were analysed. They were obtained from both ambulatory and hospitalized kidney transplanted patients with and without diarrhea after transplant. All patients were under immunosuppressive treatment with steroids, azatioprine and cyclosporine or tacrolimus. Results revealed the presence of group A rotavirus and picobimavirus in three patients suffering from severe diarrhea (33.33%). No enteric bacterial agent was isolated from these patients. The presence of viral agents was related to high levels of cyclosporine in blood (> 290 ng/ml) or prolonged immunosuppressive treatment. On the other hand, no virus was detected in any of the samples collected from asymptomatic individuals (p < 0.05). These findings suggest that viruses are implicated in the etiology of diarrheal disease in these patients.
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Diarrea/virología , Trasplante de Riñón , Infecciones por Rotavirus/complicaciones , Adulto , Argentina/epidemiología , Femenino , Gastroenteritis/virología , Humanos , Masculino , Persona de Mediana Edad , Picobirnavirus , Rotavirus , Infecciones por Rotavirus/epidemiologíaAsunto(s)
Hepatitis C/mortalidad , Trasplante de Riñón/mortalidad , Carga Viral , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/diagnóstico , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/análisis , Resultado del TratamientoRESUMEN
The aim of this study was to report on the occurrence of conventional and emerging viral agents as well as their etiological link with diarrhea in kidney transplanted subjects from Cordoba, Argentina. A total of 42 stool samples were analysed. They were obtained from both ambulatory and hospitalized kidney transplanted patients with and without diarrhea after transplant. All patients were under immunosuppressive treatment with steroids, azatioprine and cyclosporine or tacrolimus. Results revealed the presence of group A rotavirus and picobimavirus in three patients suffering from severe diarrhea (33.33
). No enteric bacterial agent was isolated from these patients. The presence of viral agents was related to high levels of cyclosporine in blood (> 290 ng/ml) or prolonged immunosuppressive treatment. On the other hand, no virus was detected in any of the samples collected from asymptomatic individuals (p < 0.05). These findings suggest that viruses are implicated in the etiology of diarrheal disease in these patients.
RESUMEN
BACKGROUND: Chronic allograft nephropathy (CAN) remains a major problem in clinical transplantation. It has been associated with increased transforming growth factor (TGF-beta1). Our goal was to correlate CAN and levels of TGF-beta1 by using a novel competitive quantitative for reverse transcription-polymerase chain reaction-ELISA (RT-PCR-ELISA) assay. METHODS: We studied 12 transplantation patients (posttransplant time: 36.5+/-11.2 months, range (r): 13-52) with stable creatinine and blood pressure and varied proteinuria. A Kidney biopsy was performed in all patients. Six patients with acute tubular necrosis (ATN) immediately after transplantation were used as controls. Histopathological evaluation was based on Banff working classification criteria. We designed an heterologous RNA competitor (IC) for RT-PCR-ELISA, which co-amplified with the same primer as TGF-beta1. Products were viewed on 96-well plates labeled with probes for IC at the desired sequence. RESULTS: Results were expressed as the number of TGF-beta1 copies/microg of total RNA. Six patients showed more than 1000 mg/24 hr proteinuria (2446+/-1421 mg/24 hr, r: 1200-5000) higher CAN Banff scores, and the other six presented <1,000 mg/24 hr (348+/-267 mg/24 hr, r: 114-800). This difference was significant (P=0.01). There were not significant differences in posttransplant time, creatinine, or blood pressure between groups. TGF-beta1 levels by RT-PCR-ELISA were statistically significant (6038+/-5317, r: 1239-12100 versus 177+/-119.7, r: 51-400, P=0.04). The control group showed levels of 228+/-111, r. 140-444, P=0.04) with significant difference only for the higher proteinuria group (P=0.03). CONCLUSIONS: This study showed that those patients with elevated CAN scores and higher proteinuria levels had higher TGF-beta1 intragraft expression.
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Trasplante de Riñón/patología , Trasplante de Riñón/fisiología , Factor de Crecimiento Transformador beta/análisis , Factor de Crecimiento Transformador beta/genética , Adolescente , Adulto , Secuencia de Bases , Biomarcadores , Biopsia con Aguja , Presión Sanguínea , Creatinina/sangre , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Necrosis Tubular Aguda/patología , Donadores Vivos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteinuria , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Donantes de Tejidos , Transcripción GenéticaRESUMEN
BACKGROUND: Cytomegalovirus (CMV) is the most prevalent viral disease in solid organ transplantation. Detection of CMV DNA in peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) frequently occurs in renal allograft recipients, yielding false positive results in seropositive patients free of CMV disease. We evaluated the clinical utility of a quantitative PCR-enzyme-linked immunosorbent assay (ELISA) for identifying patients with CMV disease. METHODS: Three hundred and fifty samples from 65 consecutive renal transplant recipients were studied. DNA was extracted from PBMC weekly up to the day of discharge and after any further admission. Samples were tested by a qualitative PCR method, and all positive samples were further studied by a quantitative PCR-ELISA method. The quantitative PCR-ELISA method used an internal standard (IS) that contained the primer sequences used in the qualitative CMV PCR. Detection and quantification was performed in 96-well plates coated with IS or CMV specific probes. RESULTS: Forty-one of 65 patients (63.1%) showed positive results by the qualitative PCR, but only 8 of these patients were diagnosed with CMV disease. Positive samples were re-analyzed by the quantitative assay. The 8 patients with CMV disease had a mean CMV viral load of 1,438+/-687 viral copies (VC)/10(6) PBMC, and the 33 without CMV disease had a mean value of 219.6+/-117.2 VC/10(6) PBMC (P<0.01). None of the 33 patients without CMV disease had viral loads higher than 500 VC/10(6) PBMC. Using 500 VC/10(6) PBMC as a cut-off value for CMV disease, the quantitative PCR showed a sensitivity and specificity of 100% compare to clinical diagnosis. CONCLUSION: CMV viral load may be useful in the diagnosis of CMV disease in renal transplant patients.
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Citomegalovirus/aislamiento & purificación , Trasplante de Riñón , Carga Viral , Adolescente , Adulto , Niño , Infecciones por Citomegalovirus/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Urinary excretion of aluminium after a successful transplant can reverse pre-transplant aluminium intoxication. We have evaluated the time course of urinary aluminium excretion and its correlation with several parameters of renal function and mineral metabolism in 49 patients (33 men and 16 women) with a wide range of pre-transplant serum aluminium concentrations, performing sequential determinations at pre-transplant time and at 7, 30, 60, and 90 post-transplant days. Mean serum aluminium at pre-transplant was 54.5+/-46.8 microg/l decreasing progressively to 28.7+/-24.4 microg/l at 90 days (P<0.0002), paralleling the decrease in serum creatinine. Urinary aluminium decreased from 63.0+/-77.9 to 52.4+/-55.9 microg/l at 90 days (P<0.0001). The maximum urinary aluminium/creatinine was 1.8+/-2.7 at 7 days and was associated with the greatest fractional excretion of sodium (4.7+/-5.1%), and the lowest tubular reabsorption of phosphate (55.7+/-25.1%). The fractional excretion of aluminium was also greatest at day 7 (1.1+/-0.9%) when serum creatinine was still elevated (3.6+/-2.3 mg/dl). At each period of time after transplantation fractional excretion of aluminium was similar in all patients despite disparate serum aluminium concentrations. Fractional excretion of aluminium was highest in those patients who developed post-Tx acute tubular necrosis (0.7+/-0.5 vs 1.5+/-1.0%, P=0.008). We found a direct positive correlation (r=0.43; P<0.002) between urinary aluminium and urinary phosphate. Basal levels and sequential changes in serum PTH, calcium, and phosphate did not correlated with fractional excretion of aluminium. These findings suggest: (i) urinary aluminium remains elevated during prolonged periods after transplant and is probably a marker of pre-transplant tissue aluminium accumulation; (ii) post-transplant fractional excretion of aluminium seems to correlated positively with other evidences of renal tubular dysfunction. Early post-transplant tubular malfunction could significantly enhance urinary aluminium elimination.