OBJETIVO: Avaliar a evolução clínica de pacientes submetidos a transplante de rim, portadores de doença arterial coronariana, que foram tratados com implante de stent coronariano (ATC-ST). MÉTODOS: Entre julho de 1998 e novembro de 2004, foram realizados, no total, 3.334 transplantes de rim em nossa Instituição (Hospital do Rim e Hipertensão). Desse total, 33 pacientes previamente submetidos a transplante de rim fizeram ATC-ST para o tratamento de 62 estenoses graves em 54 artérias coronárias, nos quais foi realizada análise retrospectiva. O registro dos eventos clínicos foi feito por meio de análise do prontuário médico, consulta médica e ligações telefônicas. RESULTADOS: No seguimento clínico de 30 meses, após a ATC-ST, observou-se que 67% dos pacientes permaneceram assintomáticos, 18% dos pacientes apresentaram quadro de angina estável, 6% apresentaram síndrome coronariana aguda sem supra de ST e 3% apresentaram síndrome coronariana aguda com supra de ST. Não houve pacientes com acidente vascular cerebral, insuficiência cardíaca congestiva ou morte cardíaca. Houve três mortes não-cardíacas. Foi observado índice de reestenose de 9%, que é comparável ao dos estudos de stent farmacológico. CONCLUSÃO: Concluímos que pacientes submetidos a transplante de rim que desenvolveram doença arterial coronariana e que foram tratados com stent coronariano tiveram baixo porcentual de reestenose clínica, provavelmente relacionado ao regime de imunossupressão administrado para evitar rejeição renal.
Hospital do Rim e Hipertensão – Universidade Federal de São Paulo – Escola Paulista de Medicina (UNIFESP – EPM) - São Paulo, SP
Nos Estados Unidos, no período entre 1997 e 1999, foram registrados 275 mil pacientes com insuficiência renal crônica (IRC) em programa de diálise, com 239 mortes/1.000 pacientes/ano, sendo 44% dos óbitos decorrentes de doença cardiovascular. Nesse mesmo período, 107 mil pacientes foram submetidos a transplante de rim, com 34 mortes/1.000 pacientes/ano, sendo 41% dos óbitos decorrentes de doença cardiovascular. A menor mortalidade nos pacientes submetidos a transplante está relacionada a fatores como seleção de pacientes de menor risco para o transplante e redução do risco pelo próprio transplante. É importante observar que, a despeito da menor mortalidade dos pacientes submetidos a transplante comparativamente à dos pacientes em programa de diálise, a doença cardiovascular mantém-se como principal causa de morte1-5.
Portadores de IRC associada a diabete melito apresentam risco maior de morte (70%) em sete anos5-7. É importante ressaltar que a maior parte dos portadores de IRC apresenta diabete melito associado.
Portadores de IRC tratados com angioplastia com
A IRC é um preditor de reestenose intra-
O uso de ciclosporina em estudos experimentais tem demonstrado inibição da proliferação da célula muscular lisa em resposta a injúria vascular15,16. O uso de prednisona em pacientes submetidos a angioplastia e que tinham níveis altos de proteína C-reativa titulada (PCR-t) demonstrou redução tanto dos eventos clínicos como da reestenose angiográfica17.
Demonstramos previamente, por meio de ultra-som intracoronariano, que há mínima hiperplasia intimal intra-
Não existem, na literatura, dados a respeito de como seria a evolução clínica e as taxas de reestenose clínica e de progressão de doença arterial coronariana (DAC) nessa população de pacientes submetidos a transplante de rim que fizeram angioplastia coronariana com implante de
O objetivo deste estudo foi avaliar a evolução clínica de pacientes submetidos a transplante de rim, portadores de DAC e tratados com ATC-ST, sendo considerados na evolução clínica todos os eventos cardiovasculares: reestenose clínica, síndrome coronariana aguda com supra de ST (SCACSST) e síndrome coronariana aguda sem supra de ST (SCASSST), acidente vascular cerebral (AVC), insuficiência cardíaca congestiva (ICC) e morte.
Entre julho de 1998 e novembro de 2004, foram realizados, no total, 3.334 transplantes de rim em nossa Instituição (Hospital do Rim e Hipertensão - HRH) (
O registro dos eventos clínicos foi feito por meio de análise do prontuário médico, de consulta médica e de ligações telefônicas.
Foram analisadas as características demográficas, os fatores de risco para doença cardiovascular, as drogas imunossupressoras em uso, as drogas cardiovasculares em uso no período da angioplastia, o tempo de diálise antes do transplante, o tipo de doador, quantas artérias coronárias foram submetidas a angioplastia, o número de
Os pacientes foram submetidos a novo cateterismo cardíaco quando apresentavam sintomas de DAC ou quando tinham exame não-invasivo positivo para isquemia miocárdica.
Foram incluídos 33 pacientes, com mediana de tempo entre o transplante de rim e o implante do
Todos os pacientes faziam uso rotineiro, ao menos três dias antes do implante do
A mediana de tempo de diálise até o transplante de rim foi de 12 meses, variando de pacientes que não fizeram diálise até aqueles que fizeram diálise por 84 meses.
Cinqüenta e cinco por cento dos pacientes submetidos a transplante renal receberam o órgão de doador vivo.
O regime de imunossupressão foi distribuído da seguinte forma: 90%, prednisona; 70%, ciclosporina; 64%, azatioprina; 33%, micofenolato de mofetil; e 12%, tacrolimus.
As indicações de angioplastia coronariana foram por SCASSST em 67%, por SCACSST em 18%, e por angina estável em 15%. Os
A mediana de seguimento clínico foi de 30 meses (variando de 6 meses a 82 meses). Foi observada boa evolução clínica, com 64% dos pacientes permanecendo assintomáticos, 18% mantendo quadro de angina estável, 6% apresentando quadro de SCASSST e 3% apresentando quadro de SCACSST. Não houve registro de pacientes com AVC ou de pacientes com ICC após o procedimento. Não houve registro de morte cardíaca, e foram registradas três mortes não-cardíacas: duas por sepse urinária e uma por adenocarcinoma de cólon sigmóide. Os dados sobre a evolução clínica após implante de
Três pacientes apresentaram reestenose clínica, definida como estenose intra-
Foi observado baixo índice de reestenose clínica (9%) nessa população de alto risco para reestenose: 45% dos pacientes submetidos a transplante de rim eram portadores de diabete melito, a maioria deles em uso de insulina, e alta média de implante de
A maioria dos pacientes submetidos a ATC-ST manteve-se sem sintomas, com poucos registros de eventos cardiovasculares maiores. Houve baixo porcentual de progressão da DAC, provavelmente em decorrência de acompanhamento clínico por curto período de alguns pacientes nessa série de 33 pacientes.
A seguir estão destacados alguns pontos indicados como de limitação deste estudo: nem todos os pacientes foram submetidos a cineangiocoronariografia, porque não seria ético submeter os assintomáticos a novo exame invasivo; não dispomos dos níveis séricos dos imunossupressores de todos os pacientes para tentarmos correlacioná-los às taxas de reestenose; não há poder estatístico, pelo pequeno número de pacientes, para saber qual imunossupressor teve maior impacto na redução da reestenose clínica; e, finalmente, por se tratar de estudo observacional e retrospectivo, que teve por objetivo a análise clínica de seus pacientes, não foram analisadas outras variáveis mecanicísticas e substitutivas, como diâmetros de referência dos vasos, extensão da estenose, extensão de
Pacientes submetidos a transplante de rim que desenvolveram DAC e que foram tratados com
Fábio Monteiro Mota Rua Napoleão de Barros, 715 – Térreo 04024-002 – São Paulo, SP E-mail:
Artigo recebido em 29/07/06; revisado recebido em 14/09/06; aceito em 14/09/06.
OBJECTIVE: To assess the clinical outcome of renal transplant patients who developed coronary artery disease and were treated with coronary stenting (TCA-ST). METHODS: A total of 3,334 renal transplants were performed in our service - Hospital do Rim e Hipertensão - HRH (Kidney and Hypertension Hospital) from July, 1998 to November, 2004. During this period, 33 of the renal transplant patients underwent TCA-ST to treat 62 severe stenoses in 54 coronary arteries. A retrospective analysis was performed with renal transplant patients undergoing TCA-ST at HRH. The clinical events were registered using medical charts, medical visits and phone calls. RESULTS: During the 30-month clinical follow-up after TCA-ST, 67% of the patients remained asymptomatic, 18% presented stable angina, 6% presented acute coronary syndrome without ST-segment elevation (ACSWSTE), and 3% presented acute coronary syndrome with ST-segment elevation (ACSSTE). No strokes, CHF or cardiac deaths were observed. Three non-cardiac deaths occurred. A restenosis rate of 9% was observed, which is comparable to those found in studies on drug-eluting stents. CONCLUSION: In conclusion, renal transplant patients who developed CAD and were treated with coronary stenting had a low rate of in-stent restenosis, probably related to the immunosuppressive regimen given to prevent kidney rejection.
Hospital do Rim e Hipertensão – Universidade Federal de São Paulo – Escola Paulista de Medicina (UNIFESP – EPM) - São Paulo, SP - Brazil
Two hundred seventy five thousand patients with chronic renal failure (CRF) undergoing dialysis were registered in the United States, from 1997 to 1999, with 239 deaths/1000 patients/year. Cardiovascular diseases were the cause of death in 44% of the cases. In the same period, 107 thousand renal transplant patients were registered. Mortality in this population was 34 deaths/1000 patients/year, of which 41% resulted from cardiovascular diseases. The lower mortality in transplant patients is related to factors such as selection of patients at a lower risk for transplantation and risk reduction resulting from the transplantation itself. It is important to observe that despite the lower mortality of transplant patients when compared to that of patients undergoing dialysis, cardiovascular diseases remain the main cause of death1-5.
Patients with CRF associated with diabetes mellitus have a higher risk of death of 70% in 7 years5-7. It is worth pointing out that the majority of patients with CRF present associated diabetes mellitus.
CRF patients undergoing stent angioplasty present a 2.2-fold higher need for repeated target vessel revascularization when compared to non-CRF patients (35%
CRF is a predictor of in-stent restenosis, with an angiographic restenosis rate after balloon angioplasty of approximately 60 to 81%10,11 and clinical restenosis rate after stent implantation of approximately 10 to 50%12,13,14.
The use of cyclosporine in experimental studies has demonstrated inhibition of smooth muscle cell proliferation in response to vascular injury15,16. The use of prednisone in patients undergoing angioplasty and who had high CRP levels demonstrated a reduction of clinical events and of angiographic restenosis17.
Using intracoronary ultrasound, we have previously demonstrated a minimal in-stent intimal hyperplasia in the group of renal transplant patients using routine immunosuppressive regimen18.
Data on the clinical course, clinical restenosis rates, and progression of the coronary artery disease (CAD) in this population of renal transplant patients undergoing coronary angioplasty with stenting (TCA-ST) are not available in the literature.
The objective of this study was to assess the clinical course of renal transplant patients with CAD, undergoing TCA-ST. The following cardiovascular events were considered in the clinical course: clinical restenosis, acute coronary syndrome with ST-segment elevation (ACSSTE), acute coronary syndrome without ST-segment elevation (ACSWSTE), stroke, congestive heart failure (CHF), and death.
A total of 3,334 renal transplants were performed in our service,
A retrospective analysis of the renal transplant patients routinely using conventional immunosuppression with cyclosporine, azathioprine, prednisone, mycophenolate mofetil, or tacrolimus, and who had undergone TCA-ST was performed at HRH.
Patients using oral rapamycin, patients who used drug-eluting stents, patients undergoing TCA-ST prior to renal transplantation, and those with unavailable clinical follow-up were not included.
The clinical events were registered using medical charts, medical visits and phone calls.
Demographic characteristics, risk factors for cardiovascular diseases, immunosuppressive drugs used, cardiovascular drugs used by the time of angioplasty, dialysis time prior to transplantation, the type of donor, number of stented coronary arteries, number of stents implanted, and the clinical course for at least six months after TCA-ST were analyzed.
Patients underwent repeat cardiac catheterization when presenting symptoms of CAD, or when presenting a non-invasive test positive for myocardial ischemia.
A total of 33 patients with a median time between renal transplantation and coronary stenting of 37 months (ranging from three days to 121 months) were included. Demographic characteristics of these patients are shown in
All patients were using aspirin and thienopyridine derivatives routinely for at least three days prior to stent implantation. Aspirin was maintained continuously, and thienopyridine derivatives for at least 30 days after TCA-ST (
The median dialysis time until renal transplantation was 12 months, ranging from patients who did not undergo dialysis to those who underwent dialysis for 84 months.
Fifty five percent of the patients received renal transplants from living donors.
Immunosuppression regimen was distributed as follows: 90% prednisone, 70% cyclosporine, 64% azathioprine, 33% mycophenolate mofetil, and 12% tacrolimus.
Indications for coronary angioplasty were: ACSWSTE in 67%, ACSSTE in 18%, and stable angina in 15%.
All stents were successfully implanted and all patients were discharged with no complications within 48 hours of the procedure. A mean of 1.88 ± 1.11 stents/patient were implanted.
The median clinical follow-up period was 30 months (ranging from six months to 82 months).
A favorable clinical outcome was observed, with 67% of the patients remaining asymptomatic, 18% remaining with stable angina, 6% presenting ACSWSTE, and 3% presenting ACSSTE.
No patients with stroke were observed after the procedure. No cardiac deaths occurred. Three non-cardiac deaths occurred: two deaths due to urinary sepsis, and one death due to colon adenocarcinoma.
Three patients presented clinical restenosis, defined as an in-stent stenosis of more than 50% in a patient undergoing repeat coronary angiography, and obtaining a rate of 9%. In the analysis of restenosis by stent implanted, five stents with restenosis in 62 stents implanted were observed, with a rate of 8%.
Ten patients presented coronary artery disease progression, defined as stenosis > 50% in another site not approached by coronary angioplasty, and obtaining a rate of 30% (
A low rate of 9% clinical restenosis was found for this population at a high risk for restenosis: renal transplant patients, 45% of whom with diabetes mellitus, most of them taking insulin, and a high mean of 1.88 ± 1.11 stents per patient. These results are similar to the clinical restenosis rates of studies on drug-eluting stents in diabetic patients19. The use of a great number of stents per patient is similar to the use of approximately two stents per patient demonstrated in recent studies with drug-eluting stents in multivessel disease20.
Most of the patients undergoing TCA-ST remained asymptomatic, and few major cardiovascular events occurred. A low percentage of coronary disease progression was observed, probably because of the short follow-up period of some patients in this case series of 33 patients.
The study limitations were:
- Not all patients underwent coronary angiography, because it would not be ethical to make asymptomatic patients undergo a repeat invasive procedure.
- Serum level of immunosuppressors is not available for all patients, thus not allowing for a correlation with restenosis rates.
- Due to the small number of patients, statistical power was not achieved to determine which immunosuppressor had the highest impact on the reduction of clinical restenosis.
- This is an observational retrospective study whose objective was to perform a clinical analysis of the patients, and other mechanism and surrogate variables, such as reference vessel diameter, stenosis length, stent length per patient, minimum lumen diameter, and acute lumen gain or late lumen loss were not assessed.
Renal transplant patients who developed coronary artery disease and were treated with stent implantation presented a low percentage of clinical restenosis, probably related to the immunosuppressive regimen used to prevent kidney rejection.
Fábio Monteiro Mota Rua Napoleão de Barros, 715 – Térreo 04024-002 – São Paulo, SP - Brazil E-mail:
Manuscript received July 29, 2006; revised manuscript received September 14, 2006; accepted September 14, 2006.