Pharmacogenetics of immunosuppressant polymorphism of CYP3A5 in renal transplant recipients.

The tacrolimus is metabolized primarily by CYP3A5, a member of the single nucleotide polymorphism family. It shows cytochrome P450 (SNP) in intron 3, which consists of a change of base, G for A, producing a stop codon. The result is a nonfunctional protein (allele *3). Allele *1 is the wild type. The patients that show the allelic variant *3 in homozygosis (G/G) are slow metabolizers of the immunosuppressant, increasing its concentration in blood. In contrast, heterozygote A/G alleles *1/*3 are intermediate metabolizers, whereas those of allele *1 in homozygosis (A/A) are normal metabolizers. The aim of this study was to determine CYP 3A5 polymorphism among adult renal transplant recipients and the general Argentinean population. We analyzed 21 recipients and 36 healthy controls. All subjects gave written informed consent approved by the local committee. To determine the polymorphism, we extracted DNA from peripheral blood and used polymerase chain reaction (PCR) to amplify intron 3 of the CYP 3A5. The presence of variant was confirmed by direct sequencing. Among the controls the CYP3A5 genotype *3/*3 (G/G) was detected in 32 individuals, 4 showed *1/*3 (A/G), and none had *1/*1 (A/A); among the recipients, the results were as follows: 18, 2, and 1, respectively. The frequencies of polymorphism in both groups were similar, although they differed from those published for other populations. These results are the basis for the development of a pharmacogenomic program applied to organ transplantation. The genetic polymorphisms can determine responses to drugs. The molecular diagnosis must be transferred to clinical practice so as to guide selection of medicine and drug doses to be optimal for each individual.

[Kidney and pancreas transplantation: initial experience at a single transplant center in Argentina]. / Trasplante renopancrático. Experiencia inicial en un centro de trasplante en Argentina.

After more than 10,000 cases reported all over the world until 1998, simultaneous kidney and pancreas transplantation has become a safe clinical practice, and it may probably represent the best treatment available for diabetic patients in end-stage renal disease. Here we present our results after 12 cadaveric pancreas transplants (8 whole organ, and 4 islet transplants), performed on insulin-dependent diabetic patients. Eleven of these patients received a kidney simultaneously, and one of them required a kidney retransplantation. All vascularised pancreatic grafts were positioned intraperitoneally, anastomosed to the iliac vessels, and bladder drained. One year patient, whole pancreas, and kidney survival rates were 86%, 86% and 71%, respectively. All of these patients remain insulin and dialysis-free, the longest for 37 months. Islets for transplantation were obtained from single cadaveric donors. Fresh, unpurified cells were transplanted intraperitoneally by laparoscopy (equivalent islet yields: 3 x 10(5), 4 x 10(5), 1 x 10(6) and 5 x 10(5)). None of the islet recipients resulted insulin-independent but they all reduced daily requirements in about 40%, with better metabolic control (mean HbA1c pretransplant 9.4 +/- 1.8, vs 7.9 +/- 1.6 posttransplant). One kidney graft was lost due to venous thrombosis. Simultaneous kidney and pancreas transplantation offers the diabetic patient in end-stage renal disease a chance of independence both from dialysis and exogenous insulin. Whole pancreas transplantation has better functional outcome than islet transplantation. Nevertheless, for those diabetic patients who do not meet the criteria to receive a vascularised graft, pancreatic cells may still improve carbohydrate metabolism with minor surgical risk.

Trasplante renopancrático. Experiencia inicial en un centro de trasplante en Argentina. / [Kidney and pancreas transplantation: initial experience at a single transplant center in Argentina]

After more than 10,000 cases reported all over the world until 1998, simultaneous kidney and pancreas transplantation has become a safe clinical practice, and it may probably represent the best treatment available for diabetic patients in end-stage renal disease. Here we present our results after 12 cadaveric pancreas transplants (8 whole organ, and 4 islet transplants), performed on insulin-dependent diabetic patients. Eleven of these patients received a kidney simultaneously, and one of them required a kidney retransplantation. All vascularised pancreatic grafts were positioned intraperitoneally, anastomosed to the iliac vessels, and bladder drained. One year patient, whole pancreas, and kidney survival rates were 86

, 86

and 71

, respectively. All of these patients remain insulin and dialysis-free, the longest for 37 months. Islets for transplantation were obtained from single cadaveric donors. Fresh, unpurified cells were transplanted intraperitoneally by laparoscopy (equivalent islet yields: 3 x 10(5), 4 x 10(5), 1 x 10(6) and 5 x 10(5)). None of the islet recipients resulted insulin-independent but they all reduced daily requirements in about 40

, with better metabolic control (mean HbA1c pretransplant 9.4 +/- 1.8, vs 7.9 +/- 1.6 posttransplant). One kidney graft was lost due to venous thrombosis. Simultaneous kidney and pancreas transplantation offers the diabetic patient in end-stage renal disease a chance of independence both from dialysis and exogenous insulin. Whole pancreas transplantation has better functional outcome than islet transplantation. Nevertheless, for those diabetic patients who do not meet the criteria to receive a vascularised graft, pancreatic cells may still improve carbohydrate metabolism with minor surgical risk.

Fístula urinaria en el trasplante renal / Urinary fistula in the renal transplantation

Entre agosto de 1988 y diciembre de 1995 se realizaron 73 trasplantes renales en el Hospital Italiano de Buenos Aires. El seguimiento medio fue de 35 meses. Se evaluó la incidencia de fístula urinaria ureterovésical y la repercusión de la misma en la evolución del implante renal. Se constataron 6 casos de fístula. En todos los casos el diagnóstico fue clínico (dolor abdominal, caída del ritmo diurético, pérdida de orina por la herida) y en algunos casos se emplearon, además la cistografía y ecografía para la evaluación de esyos pacientes. El tiempo trancurrido al momento del diagnóstico fue menor de 24 hrs. en cuatro pacientes y mayor de 72 hrs. en los restantes. La resolución fue quirúgica en todos los casos (reimplante ureterovesical). La incidencia de fístula urinaria fie del 8,21 por ciento (seis pacientes). De los pacientes en los que el diagnóstico fue precoz tres conservan una función renal aceptable y el cuarto quedó con función renal alterada. Aquellos en los que el diagnóstico fue más tardío presentaron en el seguimiento estenosis ureterovesical (18 meses). Los estudios por imágenes utilizados en la evaluación de algunos de estos pacientes no fueron utilidad para llegar al diagnóstico. El seguimiento estricto en el postoperatorio inmediato y un diagnóstico precoz son cruciales para el tratamiento adecuado d esta complicación. Los estudios imagenológicos no aportaron infor mación para decidir la conducta. En los pacientes que presentaron fístula se observó una mayor incidencia de estenosis ureterovesical en el seguimiento a lar go plazo (33 por ciento)