Gentil Alves Filho

Everolimus with Optimized Cyclosporine Dosing in Renal Transplant Recipients: 6-Month Safety and Efficacy Results of Two Randomized Studies

Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and low‐exposure cyclosporine (CsA) (C2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n = 237) had no induction therapy; in Study 2 (A2307; n = 256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post‐transplant. Median creatinine levels in Study 1 were 133 and 132 μmol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 μmol/L in both groups in Study 2. Biopsy‐proven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough < 3 ng/mL. There were no significant between‐group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between‐group differences in adverse events in either study. Concentration‐controlled everolimus with low‐exposure CsA provided effective protection against rejection with good renal function.

Quality of life in renal transplant patients: impact of a functioning graft

Objective measures to evaluate quality of life are gaining importance as an adjuvant in assessing therapeutic interventions. The study purpose was to compare quality of life in renal transplant patients with functioning graft and those who restarted dialysis after graft loss. Quality of life was measured using the World Health Organization Quality of Life questionnaire (WHOQOL-Bref). One hundred and thirty two patients were interviewed, and divided into two groups: group I, 100 patients on regular follow-up in outpatient clinics and stable graft functioning; and group II, 32 patients who restarted dialysis after graft loss. The WHOQOL-Bref showed better quality of life in those renal transplant patients with a functioning graft, especially regarding the physical and psychological domains assessed in the general questions. There were no differences between the groups in the social relationship and environmental domains. WHOQOL-Bref is an efficient tool and can be useful for better approaching these patients, not only on a medical basis.

Use of aminophylline and enalapril in posttransplant polycythemia.

BACKGROUND Posttransplant polycythemia (PTP) affects 6-30% of renal transplant recipients and can result in thromboembolic disease. The pathogenesis of PTP remains unknown and may be multifactorial. Although phlebotomy has previously been the treatment for PTP, drugs such as adenosine receptor antagonists or angiotensin-converting enzyme inhibitors can be used to control PTP. METHODS The authors performed a prospective study of two different drugs to treat PTP: aminophylline and enalapril. Twenty-seven patients with PTP lasting more than 6 months were evaluated. During phase 1, aminophylline was compared with enalapril. The patients sequentially received aminophylline and enalapril during 12-week periods, intercalated by 12-week periods of no drugs. During phase 2, enalapril was administered for 12 weeks. RESULTS From January 1984 to December 1993, 110 of 333 patients with PTP lasting more than 6 months (33%) developed polycythemia, and 27 patients were included in the present study. In phase 1, aminophylline had no effect on PTP. Enalapril promoted an erythropoiesis inhibition, characterized by a decrease in hematocrit and an increase in iron stores and ferritin levels. After withdrawal of enalapril, the hematocrit increased and the iron stores decreased. In phase 2, there was a progressive reduction in hematocrit after the 4th week of therapy. The lowest hematocrit was observed in the 12th week and then enalapril was stopped, leading to a subsequent rise in hematocrit. Erythropoietin levels and renal function remained constant during all periods of both phases of the study. CONCLUSION The use of adenosine antagonists was ineffective to treat PTP in our series. However, treatment with enalapril promoted an erythropoiesis inhibition, demonstrated by a reduction in hematocrit, hemoglobin, red blood cell count, and reticulocyte count, associated with an increase in iron stores. This response occurred independently from erythropoietin levels or hemodynamic graft changes.

The prevalence of TT virus infection in renal transplant recipients in Brazil.

Background. Recently, TT virus (TTV) was discovered as a potential causative agent for non-A-E hepatitis.Little is known about the prevalence of TTV infection in renal transplant recipients. Methods. One hundred and seventeen Brazilian renal transplant recipients and 100 normal subjects were examined to determine the prevalence of TTV infection. The TTV DNA in serum and its genotype were examined using polymerase chain reaction and restriction enzyme length polymorphism, respectively. Results. TTV DNA was detected in 63/117 (53.8%) renal transplant recipients in contrast to its detection in 10/100 (10%) normal subjects (P <0.001). There was no statistical difference in the distribution of TTV genotypes between these groups. There was no significant difference in clinical backgrounds between TTV positive and negative patients. Conclusions. These results indicate a risk for TTV infection in renal transplant recipients in Brazil. They also indicate that TTV itself might not have a strong correlation with the pathogenicity of liver diseases.

Influência da técnica anestésica nas alterações hemodinâmicas no transplante renal: estudo retrospectivo

JUSTIFICATIVA Y OBJETIVOS: El exito en el transplante renal (Tx) depende del tipo de donador, de la duracion de la isquemia fria y de los parametros hemodinamicos en la reperfusion. El objetivo de esta investigacion fue analizar la tecnica anestesica, la incidencia de alteraciones cardiovasculares y el aparecimiento de diuresis en el periodo perioperatorio de los Tx realizados en la UNICAMP. METODO: Se evaluo retrospectivamente Tx de adultos realizados entre enero de 2005 y abril de 2006. Se tuvieron en cuenta los datos demograficos, los examenes laboratoriales preoperatorios, tecnicas y agentes anestesicos, hidratacion, parametros hemodinamicos, el uso de aminas vasoactivas, la presencia de diuresis y complicaciones intraoperatorias, con analisis comparativo entre los subgrupos formados conforme a la tecnica anestesica empleada. Se usaron en el analisis estadistico el test t de Student (parametricos), Mann-Whitney (no parametricos), test del Cui-cuadrado y Exacto de Fisher para la comparacion de proporciones y analisis multivariada. RESULTADOS: Se estudiaron 92 pacientes, 59 con anestesia general (AG) y 33 anestesia general asociada a la epidural (AG + Peri), 42 recibieron rinones de donantes vivos y 50 de fallecidos. No hubo diferencia (p < 0,05) en la mayoria de los parametros preoperatorios estudiados, con excepcion del origen del injerto (82% AG + Peri recibieron rinones de donante fallecido). La alteracion cardiovascular mas frecuente fue la hipotension arterial (30% AG y 48% AG + Peri, p < 0,05). El regimen de hidratacion no fue diferente entre los grupos (86,7 ± 30,2 mL.kg-1 AG y 94,8 ± 21,8 mL.kg-1 AG+Peri, p = 0,38). El injerto del donante fallecido se correlaciono con una mayor inestabilidad hemodinamica y con un peor pronostico para la funcion inmediata del injerto, p < 0,01 y 0,01 respectivamente. Un volumen de hidratacion de 80 mL.kg-1 se asocio a la diuresis (OR = 2,94, IC95% 1,00-8,32). CONCLUSIONES: La tecnica anestesica empleada fue anestesia general, asociada o no a la epidural. La alteracion hemodinamica mas comun fue la hipotension arterial. Se mostraron beneficos con relacion a la diuresis por ser de un receptor de donante vivo y recibir una hidratacion de 80 mL.kg-1 de solucion fisiologica a 0,9%.BACKGROUND AND OBJECTIVES The success of renal transplantation (Tx) depends on the type of donor, length of cold ischemia, and hemodynamic parameters on reperfusion. The objective of this study was to analyze the anesthetic technique, the incidence of cardiovascular changes, and the presence of postoperative diuresis of Tx performed at UNICAMP. METHODS Renal transplantation of adults performed from January 2005 and April 2006 were evaluated retrospectively. Demographic data, preoperative laboratorial exams, anesthetic techniques and agents, hydration, hemodynamic parameters, use of vasoactive amines, presence of a diuresis, and intraoperative complications were evaluated, and comparative analysis between the subgroups, formed according to the anesthetic technique, was undertaken. The Student t test (parametric), Mann-Whitney test (non-parametric), Chi-square test and Fisher Exact test for comparison of proportions and multivariate analysis were used. RESULTS Ninety-two patients were evaluated; 59 underwent general anesthesia (GA) and 33 underwent general anesthesia associated with epidural block (GA + Epi); 42 patients received live-donor transplants and 50 from dead donors. Most preoperative parameters analyzed did not show statistically significant differences (p > 0.05), except for the origin of the graft (82% of GA + Epi received dead donor kidneys). Hypotension (30% GA and 48% GA + Epi, p < 0.05) was the most frequent cardiovascular change. The hydration regimen did not differ between both groups (86.7+/- 30.2 mL.kg(-1) GA and 94.8 +/- 21.8 mL.kg(-1) GA+Epi, p = 0.38). Dead donor grafts were more commonly associated with hemodynamic instability and worse prognosis for the immediate function of the graft, p < 0.01 and 0.01, respectively. Hydration of 80 mL.kg(-1) was associated with the presence of diuresis (OR = 2.94, CI 95% 1.00-8.32). CONCLUSIONS General anesthesia associated or not with epidural block was the anesthetic technique used. Hypotension was the most common hemodynamic change. Live-donor graft and volume of hydration of 80 mL.kg(-1) of NS favored diuresis.

Influence of the anesthetic technique on the hemodynamic changes in renal transplantation: a retrospective study

JUSTIFICATIVA Y OBJETIVOS: El exito en el transplante renal (Tx) depende del tipo de donador, de la duracion de la isquemia fria y de los parametros hemodinamicos en la reperfusion. El objetivo de esta investigacion fue analizar la tecnica anestesica, la incidencia de alteraciones cardiovasculares y el aparecimiento de diuresis en el periodo perioperatorio de los Tx realizados en la UNICAMP. METODO: Se evaluo retrospectivamente Tx de adultos realizados entre enero de 2005 y abril de 2006. Se tuvieron en cuenta los datos demograficos, los examenes laboratoriales preoperatorios, tecnicas y agentes anestesicos, hidratacion, parametros hemodinamicos, el uso de aminas vasoactivas, la presencia de diuresis y complicaciones intraoperatorias, con analisis comparativo entre los subgrupos formados conforme a la tecnica anestesica empleada. Se usaron en el analisis estadistico el test t de Student (parametricos), Mann-Whitney (no parametricos), test del Cui-cuadrado y Exacto de Fisher para la comparacion de proporciones y analisis multivariada. RESULTADOS: Se estudiaron 92 pacientes, 59 con anestesia general (AG) y 33 anestesia general asociada a la epidural (AG + Peri), 42 recibieron rinones de donantes vivos y 50 de fallecidos. No hubo diferencia (p < 0,05) en la mayoria de los parametros preoperatorios estudiados, con excepcion del origen del injerto (82% AG + Peri recibieron rinones de donante fallecido). La alteracion cardiovascular mas frecuente fue la hipotension arterial (30% AG y 48% AG + Peri, p < 0,05). El regimen de hidratacion no fue diferente entre los grupos (86,7 ± 30,2 mL.kg-1 AG y 94,8 ± 21,8 mL.kg-1 AG+Peri, p = 0,38). El injerto del donante fallecido se correlaciono con una mayor inestabilidad hemodinamica y con un peor pronostico para la funcion inmediata del injerto, p < 0,01 y 0,01 respectivamente. Un volumen de hidratacion de 80 mL.kg-1 se asocio a la diuresis (OR = 2,94, IC95% 1,00-8,32). CONCLUSIONES: La tecnica anestesica empleada fue anestesia general, asociada o no a la epidural. La alteracion hemodinamica mas comun fue la hipotension arterial. Se mostraron beneficos con relacion a la diuresis por ser de un receptor de donante vivo y recibir una hidratacion de 80 mL.kg-1 de solucion fisiologica a 0,9%.BACKGROUND AND OBJECTIVES The success of renal transplantation (Tx) depends on the type of donor, length of cold ischemia, and hemodynamic parameters on reperfusion. The objective of this study was to analyze the anesthetic technique, the incidence of cardiovascular changes, and the presence of postoperative diuresis of Tx performed at UNICAMP. METHODS Renal transplantation of adults performed from January 2005 and April 2006 were evaluated retrospectively. Demographic data, preoperative laboratorial exams, anesthetic techniques and agents, hydration, hemodynamic parameters, use of vasoactive amines, presence of a diuresis, and intraoperative complications were evaluated, and comparative analysis between the subgroups, formed according to the anesthetic technique, was undertaken. The Student t test (parametric), Mann-Whitney test (non-parametric), Chi-square test and Fisher Exact test for comparison of proportions and multivariate analysis were used. RESULTS Ninety-two patients were evaluated; 59 underwent general anesthesia (GA) and 33 underwent general anesthesia associated with epidural block (GA + Epi); 42 patients received live-donor transplants and 50 from dead donors. Most preoperative parameters analyzed did not show statistically significant differences (p > 0.05), except for the origin of the graft (82% of GA + Epi received dead donor kidneys). Hypotension (30% GA and 48% GA + Epi, p < 0.05) was the most frequent cardiovascular change. The hydration regimen did not differ between both groups (86.7+/- 30.2 mL.kg(-1) GA and 94.8 +/- 21.8 mL.kg(-1) GA+Epi, p = 0.38). Dead donor grafts were more commonly associated with hemodynamic instability and worse prognosis for the immediate function of the graft, p < 0.01 and 0.01, respectively. Hydration of 80 mL.kg(-1) was associated with the presence of diuresis (OR = 2.94, CI 95% 1.00-8.32). CONCLUSIONS General anesthesia associated or not with epidural block was the anesthetic technique used. Hypotension was the most common hemodynamic change. Live-donor graft and volume of hydration of 80 mL.kg(-1) of NS favored diuresis.

Percutaneous renal graft biopsy: a clinical, laboratory and pathological analysis

CONTEXT Renal allograft biopsies have been used as a good method for monitoring the evolution of kidney transplants for at least 20 years. Histological analysis permits differential diagnosis of the causes of allograft dysfunction to be made. OBJECTIVES To correlate the data of urinalysis and serum creatinine with histological diagnosis of renal graft in a group of renal transplant patients. DESIGN Accuracy study, retrospective analysis. SETTING A university terciary referral center. SAMPLE 339 percutaneous allograft biopsies obtained from 153 patients. Blood and urine samples were obtained before the graft biopsy. MAIN MEASUREMENTS Laboratory evaluation and hystological analysis (light microscopy, immunofluorescent electronic microscopy). RESULTS Most of the biopsies (58.9%) were performed during the first month post-transplant. An increase in serum creatinine was associated with acute tubular and/or cortical necrosis. Proteinuria and normal serum creatinine were associated with glomerular lesions. Non-nephrotic range proteinuria and an increase in serum creatinine were associated with chronic rejection. CONCLUSION Evaluation of serum creatinine and urinalysis can be useful in suggesting the histological graft diagnosis.

Gastric emptying study by scintigraphy in patients with chronic renal failure

BACKGROUND AND OBJECTIVES This study had the purpose of studying gastric emptying in patients with chronic renal failure. MATERIAL AND METHOD Thirty patients with chronic renal failure were studied, 16 in conservative clinical treatment and 14 in hemodialysis for over six months. The control group (CTL) was composed of 18 asymptomatic volunteers. The method of gastric emptying study was scintigraphy. The standardized test meal was an omelet of three chicken eggs prepared with colloidal sulfur marked with 185 MBq of 99m technetium. Gastric retention curves were studied and T½ of gastric emptying was obtained from them. A T½ value corresponding to the average of T½ values of control group plus twice standard deviation was considered nornmal. Statistical tests used were χ(2) and Kruskal-Wallis. RESULTS There was no statistically significant difference with regard to total gastric retention curves and T½ of gastric emptying, which was similar in three studied groups. Nine patients had high T½ of gastric emptying, above 125 minutes. These patients were equally distributed among both genders and conservative clinical treatment and hemodialysis groups. CONCLUSIONS We concluded that gastric retention rate and T½ of gastric emptying in patients with chronic renal failure in conservative clinical treatment and hemodialysis does not differ from the healthy patients group. Hemodialysis does not seem to reduce the risk of gastric retention in patients with chronic renal failure.

O esvaziamento gástrico e a insuficiência renal crônica

BACKGROUND AND OBJECTIVES The first reference to delayed gastric emptying (GE) was made by Grodstein in 1979. Other studies have since been published, not always confirming his work. The importance of GE in anesthesia can be resumed by one of its main aspects, preoperative fasting. Delayed gastric emptying can lead to stasis and increase the risk of vomiting and aspiration. The possibility that uremic patients present delayed gastric emptying is fascinating. Gastric complaints are common in this patient population, and could be explained by the difficulty to empty the stomach. Despite the evidence, there is controversy in the literature regarding this subject. There is no consensus regarding the results. Differences in the methods of the studies could explain the results obtained in clinical and experimental trials. The objective of this study was to review a few important aspects of the dyspeptic syndrome in patients with chronic renal failure (CRF), emphasizing the delayed GE. CONTENTS The basic aspects of the physiology of GE, methods used more often to study GE, dyspeptic syndrome and uremia, and gastric emptying in chronic renal failure will be discussed. CONCLUSIONS Gastric emptying is a complex physiological process that transfers food from the stomach to the duodenum, whose mechanisms are yet to be fully characterized. Scintigraphy, using meals with radiolabelled drugs, is the exam used more often to study GE. An expressive percentage of the patients with end-stage renal disease also present delayed GE. It is possible that other mechanisms, besides uremia, involved in gastric motor function also play a role in this dysfunction.INTRODUCCION Y OBJETIVOS: La primera referencia de retardo en el vaciamiento gastrico (EG) fue hecha por Grodstein en 1979. Otros estudios fueron publicados posteriormente, y no siempre confirmando esa observacion. La importancia del EG en anestesia puede ser resumida un uno de sus aspectos principales, el ayuno preoperatorio. El retardo en el vaciamiento puede causar estasis y aumentar el riesgo de vomito y aspiracion pulmonar. La posibilidad de existir retardo del vaciamiento en uremicos nos atrae. Quejas dispepticas son comunes en estos pacientes y podrian ser explicadas por la dificultad de vaciamiento gastrico. A pesar de las evidencias, la literatura es muy controvertida en este aspecto. No existe un consenso en cuanto a los resultados obtenidos. Diferencias en el metodo de estudio utilizado podrian explicar esos resultados, observados en estudios clinicos y experimentales. El objetivo de este estudio fue ver nuevamente algunos aspectos importantes del sindrome dispeptico en pacientes con insuficiencia renal cronica (IRC) terminal, con enfasis en el retardo del EG. CONTENIDO: Se abordaran los aspectos basicos relacionados a la fisiologia del EG, los metodos mas empleados para el estudio del EG, el sindrome dispeptico y la uremia y el vaciamiento gastrico en la insuficiencia renal cronica. CONCLUSIONES: El EG es un proceso fisiologico complejo de transferencia del alimento del estomago para el duodeno, cuyos mecanismos todavia no se conocen bien. La cintilografia, utilizando comidas con radio farmacos, es el examen mas utilizado para el estudio del EG. Un porcentaje expresivo de pacientes con IRC terminal presenta retardo en el EG. Posiblemente otros mecanismos, ademas de la uremia, involucrando la funcion motora gastrica, estan involucrados en esta disfuncion.

Gastric emptying and chronic renal failure

BACKGROUND AND OBJECTIVES The first reference to delayed gastric emptying (GE) was made by Grodstein in 1979. Other studies have since been published, not always confirming his work. The importance of GE in anesthesia can be resumed by one of its main aspects, preoperative fasting. Delayed gastric emptying can lead to stasis and increase the risk of vomiting and aspiration. The possibility that uremic patients present delayed gastric emptying is fascinating. Gastric complaints are common in this patient population, and could be explained by the difficulty to empty the stomach. Despite the evidence, there is controversy in the literature regarding this subject. There is no consensus regarding the results. Differences in the methods of the studies could explain the results obtained in clinical and experimental trials. The objective of this study was to review a few important aspects of the dyspeptic syndrome in patients with chronic renal failure (CRF), emphasizing the delayed GE. CONTENTS The basic aspects of the physiology of GE, methods used more often to study GE, dyspeptic syndrome and uremia, and gastric emptying in chronic renal failure will be discussed. CONCLUSIONS Gastric emptying is a complex physiological process that transfers food from the stomach to the duodenum, whose mechanisms are yet to be fully characterized. Scintigraphy, using meals with radiolabelled drugs, is the exam used more often to study GE. An expressive percentage of the patients with end-stage renal disease also present delayed GE. It is possible that other mechanisms, besides uremia, involved in gastric motor function also play a role in this dysfunction.INTRODUCCION Y OBJETIVOS: La primera referencia de retardo en el vaciamiento gastrico (EG) fue hecha por Grodstein en 1979. Otros estudios fueron publicados posteriormente, y no siempre confirmando esa observacion. La importancia del EG en anestesia puede ser resumida un uno de sus aspectos principales, el ayuno preoperatorio. El retardo en el vaciamiento puede causar estasis y aumentar el riesgo de vomito y aspiracion pulmonar. La posibilidad de existir retardo del vaciamiento en uremicos nos atrae. Quejas dispepticas son comunes en estos pacientes y podrian ser explicadas por la dificultad de vaciamiento gastrico. A pesar de las evidencias, la literatura es muy controvertida en este aspecto. No existe un consenso en cuanto a los resultados obtenidos. Diferencias en el metodo de estudio utilizado podrian explicar esos resultados, observados en estudios clinicos y experimentales. El objetivo de este estudio fue ver nuevamente algunos aspectos importantes del sindrome dispeptico en pacientes con insuficiencia renal cronica (IRC) terminal, con enfasis en el retardo del EG. CONTENIDO: Se abordaran los aspectos basicos relacionados a la fisiologia del EG, los metodos mas empleados para el estudio del EG, el sindrome dispeptico y la uremia y el vaciamiento gastrico en la insuficiencia renal cronica. CONCLUSIONES: El EG es un proceso fisiologico complejo de transferencia del alimento del estomago para el duodeno, cuyos mecanismos todavia no se conocen bien. La cintilografia, utilizando comidas con radio farmacos, es el examen mas utilizado para el estudio del EG. Un porcentaje expresivo de pacientes con IRC terminal presenta retardo en el EG. Posiblemente otros mecanismos, ademas de la uremia, involucrando la funcion motora gastrica, estan involucrados en esta disfuncion.