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- DISFUNÇÃO E PERDA DE ENXERTO RENAL: FACTORES PREDITIVOSPublication . Fonseca, Isabel
- Pancreas-Kidney Transplantation: Analysis of 150 patients from one Centre in PortugalPublication . Martins, La Salete; Fonseca, Isabel; Aguiar, P.; Rocha, A.; Costa, R.; Santos, C.; Malheiro, J.; Pedroso, S.; Almeida, M.; Dias, L.; Castro-Henriques, A.; Cabrita, A.; Davide, J.Introduction: Simultaneous pancreas-kidney transplantation (SPKT) outcomes are conditioned in the short-term mostly by post-operative complications. In the long-term, cardiovascular (CV) disease and immunological loss are the main limitations to transplant survival. Aims: To analyse retrospectively the results from 150 SPKT performed at our centre. Patients and Methods: The 81 females and 69 males had a mean age of 35±6 years; they were diabetic for 24±6 years and had been on dialysis for 30±21months (except 5 preemptive). Anti-lymphocyte globulin, tacrolimus, mycophenolate and steroids were used as immunosuppressive therapy. Deceased-donor mean age was 28±11 years. In 28.7% the transplant was performed with 6 HLA-mismatches. Results: Acute rejection’s incidence was 16%. Ten SPKT patients died; infection was the leading cause of death (five cases), followed by Cardiovascular/cerebrovascular disease (three cases). In 21 patients the pancreas failed, mainly due to thrombosis or bleeding (11 cases), and infection (five cases); in two it was due to late acute rejection. In four patients only the kidney failed, due to chronic rejection. Five patients lost both grafts, from late acute rejection in four and thrombosis in one. We analyzed the 110 SPKT patients (73.3%) with both grafts functioning. Their mean serum creatinine was 1.2±0.4mg/dl; creatinineclearance was 76±24 ml/min; fasting glycaemia was 81±10mg/dl; and HbA1c was 5.3±0.4%. Hypertension has been treated in 47.2% of patients, in the majority (28.2%) with only one drug. Hyperlipidaemia was observed in 19.1% and excessive weight (>25kg/m2) in 17.3%. Conclusions: From our cohort of SPKT, 93.3% of patients are alive, 73.3% have both grafts functioning. Rejection was the main cause of late pancreas loss. Early mortality was due to infection (3.3%). CV/cerebrovascular disease was the main cause of late mortality (2%). The prevalence of hyperlipidaemia and overweight was inferior to 20%. Hypertension was the most frequently found CV risk factor.
- Hiperhomocisteinemia no transplante renal – prevalência, distribuição e determinantesPublication . Fonseca, IsabelIntrodução: A doença cardiovascular é uma complicação major do transplante renal (TR). A hiperhomocisteinemia (HHC) é considerada actualmente, como um factor de risco independente da aterosclerose. Apenas um número limitado de estudos analisou este "novo" factor de risco na população com TR. Do nosso conhecimento, nenhum deles português. Objectivos: A realização deste estudo pretendeu: a) determinar a prevalência de HHC basal; b) analisar a distribuição dos valores plasmáticos de homocisteína basal total (HC) e de vitaminas B6, B12 e ácido fólico; c) identificar, por análise univariada e multivariável, os determinantes da concentração de HC e os factores preditores da HHC numa amostra de transplantados renais. Participantes e Métodos: Foi efectuado o doseamento analítico da HC e vitaminas B6, B12 e ácido fólico (sérico e eritrocitário) em 202 indivíduos com TR (89 Mulheres; 113 Homens), com tempo de TR superior a 6 meses. Foram também determinadas outras variáveis analíticas potencialmente relevantes e recolhidos factores demográficos e associados ao pré e ao pós TR, nomeadamente a função renal, terapêutica actual e outros factores de risco para a aterosclerose. Considerou-se a presença de HHC quando os valores excederam os 15 nmol/L Resultados: A percentagem de HHC foi de 48.7%, atingindo maioritariamente o sexo masculino, que apresentou valores de HC 22% mais elevados que o sexo feminino. A HC correlacionou-se inversa e significativamente com a concentração de vitaminas B12 (r=-0.27, p<0.001) e ácido fólico sérico (r=-0.36, p<0.001) e eritrocitário (r=-0.25, p<0.01). A correlação entre a HC e a creatinina, ureia e ácido úrico séricos foi positiva e significativa (r=0.55, p<0.001 ; r=0.49; p<0.001 e r=0.51, p<0.001, respectivamente). Os valores de HC aumentaram significativamente com o tempo de TR (r=0.21, p=0.003) e com o número de dias de internamento após o TR (r=0.25, p<0.001). Não foi obtida correlação entre a idade e a HC. Por análise de regressão linear múltipla, o ácido úrico e creatinina séricos, antecedentes de doença vascular, sexo, terapêutica com antiadrenérgicos de acção central e ácido fólico eritrocitário foram os determinantes independentes e significativos (p<0.05) da concentração de HC, permitindo explicar 46.7% da sua variação. Nenhum dos factores de risco para a aterosclerose considerados se associou significativamente com a presença de hiperhomocisteinemia, quer por análise univariada quer multivariável. Após ajuste, por regressão logística, a vitamina B12, ácido fólico eritrocitário, creatinina sérica e número de anti-hipertensores foram os factores preditores significativos da ocorrência de HHC. Conclusão: A HHC ocorreu em quase metade da nossa amostra, atingindo maioritariamente o sexo masculino. A concentração da HC tende a aumentar com a deterioração da função renal e com a diminuição dos valores de vitamina B12 e ácido fólico, apesar da ausência de défices significativos das vitaminas doseadas. Ao contrário da população geral, não foi obtida uma correlação entre a idade e a HC. A ocorrência de HHC foi independente de qualquer outro factor de risco para a aterosclerose. O ácido fólico foi um determinante significativo na concentração HC e um preditor importante da ocorrência de HHC, juntamente com a vitamina B12, o que permite sugerir a possibilidade de intervenção neste factor de risco.
- Força preensora da mão no rastreio da desnutrição - dados preliminaresPublication . Guerra, R.; Fonseca, Isabel; Pichel, F.; Restivo, T.; Amaral, T.
- Neutrophil gelatinase-associated lipocalin in kidney transplantation is an early marker of graft dysfunction and is associated with one-year renal functionPublication . Fonseca, Isabel; Carlos Oliveira, José; Almeida, M.; Cruz, M.; Malho, A.; Martins, La Salete; Dias, L.; Pedroso, S.; Santos, J.; Lobato, L.; Castro-Henriques, A.; Mendonça, D.Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3-6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function.
- Steroid Withdrawal in Simultaneous Pancreas-Kidney Transplantation:Publication . Malheiro, J.; Martins, La Salete; Fonseca, Isabel; Gomes, A.M.; Santos, J.; Dias, L.; Dores, J.; Oliveira, F.; Seca, R.; Almeida, R.; Henriques, A.; Cabrita, A.; Teixeira, M.ABSTRACT Simultaneous pancreas-kidney transplantation (SPK) is the treatment of choice for selected diabetic patients with end-stage renal disease. Maintenance steroid therapy is associated with significant morbidity and mortality among SPK transplant recipients. Steroid withdrawal regimens are becoming more common, albeit with reservations regarding its safety and efficacy. We performed retrospective review of 77 SPK transplant recipients from May 2000 to December 2007. The subjects received induction therapy with thymoglobulin followed by maintenance immunosuppression with tacrolimus and myco- phenolate mofetil. late steroid withdrawal protocol was adopted. The rates of acute rejection, graft and patient survival, and side effects were analyzed. One-year patient, kidney, and pancreas survivals were 93%91%and 86%respectively. Eleven patients experienced acute rejection. Mean follow-up time was 1155.5 776.1 days. Prednisolone withdrawal was carried out between and 12 months posttransplantation in 42 patients (77.8%with at least year follow-up; no case of acute rejection occurred. At present, 72 patients have functioning kidney graft, and 65 patients also have functioning pancreas graft. The mean serum creatinine is 1.12 0.49 mg/dL and the mean HbA1c concentration is 4.5% 0.4%The patients have low prevalence of hypertension, hyperlipidemia, and obesity. Steroid withdrawal was successful and safe in the majority of in-study patients and safe without an increase of immune events. Our patient and graft outcomes are within other international SPK transplant units standards.
- Posttransplant allosensitization in low immunological risk kidney and kidney-pancreas graft recipients.Publication . Malheiro, J.; Tafulo, S.; Dias, L.; Martins, La Salete; Fonseca, Isabel; Almeida, M.; Pedroso, S.; Freitas, F.; Beirão, I.; Castro-Henriques, A.; Cabrita, A.INTRODUCTION: Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled. METHODS: Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes. RESULTS: Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%, P = 0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1, P < 0.01), HLA mismatches >3 (HR = 10.2, P = 0.03), and antibody positivity for anti-HLA class II (HR = 5.1, P = 0.04) or class I/II (HR = 13.8, P < 0.01) were independent predictors of graft loss. CONCLUSIONS: Allosensitization against HLA class II ± I after transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.
- NIVEIS DE SUPERÓXIDO DISMUTASE REVELAM STRESS OXIDATIVO AUMENTADO NA POLINEUROPATIA AMILOIDÓTICA FAMILIARPublication . REGUENGO, HENRIQUE; Cardoso, M. L.; Coelho, T.; Martins, A.; Novais, M.; Cruz, M.; Fonseca, Isabel; Martins, B.; Marques, F.NIVEIS DE SUPERÓXIDO DISMUTASE REVELAM STRESS OXIDATIVO AUMENTADO NA POLINEUROPATIA AMILOIDÓTICA FAMILIAR Henrique Reguengo1,2, Maria Luís Cardoso2, Teresa Coelho3, Ana Martins3, Marta Novais3, Madalena Cruz1, Isabel Fonseca3, Berta Martins4, Franklim Marques2 1Serviço de Química Clínica, HSA/CHP, 2FFUP, 3Unidade Clínica de Paramiloidose, HSA/CHP, 4Laboratório de Imunogenética, ICBAS/UP. Hospital de Santo António, Centro Hospitalar do Porto (HSA/CHP), Porto. Faculdade de Farmácia, Universidade do Porto (FF/UP), Porto. Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS/UP), Porto. Introdução A polineuropatia amiloidótica familiar (PAF) é provocada por mutações no gene da transtirretina, principalmente em resultado da mutação TTRv30M no caso de Portugal. Estudos recentes em vários tipos de amiloidoses revelam que o stress oxidativo pode estar envolvido quer na produção das fibrilas de proteína amilóide, quer na modificações pós formação das fibrilas. A enzima superóxido dismutase (SOD) desempenha um importante papel antioxidante que protege as células expostas aos radicais superóxido. O presente estudo pretendeu avaliar o stress oxidativo nesta patologia. Material e Métodos A amostra em estudo incluiu 40 doentes com PAF e 45 portadores assintomáticos da mutação, seguidos habitualmente na Unidade Clínica de Paramiloidose do CHP. Foi ainda considerado um grupo controlo de 26 indivíduos saudáveis. Avaliou-se a concentração de SOD intra-eritocitária com um método colorimétrico disponível no KIT RANSOD ref SD 125 da Randox. A análise estatística foi efectuada utilizando o software SPSS, versão 19. Resultados Os valores de SOD obtidos foram os seguintes: Controlos: (1208±254 U/g Hb), Portadores assintomáticos (1436±62 U/g Hb), Doentes com PAF (1455±350 U/g Hb). Os valores resultaram da média de três réplicas. Os valores de SOD foram significativamente mais elevados no grupo de doentes com PAF e nos portadores assintomáticos, comparativamente ao grupo controlo (respectivamente P=0.003 e P=0.013). Não foram encontradas diferenças estatisticamente significativas entre os doentes com PAF e os portadores assintomáticos. No grupo de doentes com PAF verificou-se uma correlação positiva significativa entre os valores de SOD e Proteína C reactiva (r=0.45, P =0.013). Conclusão A alteração da concentração da SOD nos doentes com PAF sugere uma maior exposição dos mesmos a fenómenos de stress oxidativo comparativamente ao grupo controlo. Dado que este fenómeno pode ter influência quer no despoletar, quer no curso da patologia da doença, justifica-se uma maior atenção e estudo deste fenómeno nestes doentes. Apresentador: Henrique Reguengo, Técnico Superior de Saúde, Serviço de Quimica Clínica, HSA/CHP; Aluno de Doutoramento em Ciências Farmacêuticas, FF/UP.
- Sarcopenia em doentes hospitalizados: impacto de diferentes critérios de diagnósticoPublication . Sousa, Ana Sofia; Guerra, Rita; Fonseca, Isabel; Pichel, Fernando; Amaral, Teresa
- Predicting 6-Month Mortality in Incident Elderly Dialysis Patients: A Simple Prognostic ScorePublication . Lascasas, Josefina; Oliveira, Pedro; J, Malheiro; Campos, Andreia; Correia, Sofia; Cabrita, Antonio; Lobato, Luísa; Fonseca, IsabelAim: Mortality in end-stage renal disease (ESRD) remains high, particularly among elderly, who represents the most rapidly growing segment of the ESRD population in wealthier countries. We developed and validated a risk score in elderly patients to predict 6-month mortality after dialysis initiation. Methods: We used data from a cohort of 421 patients, aged 65 years and over who started dialysis between 2009 and 2016, in our Nephrology department. The predictive score was developed using a multivariable logistic regression analysis. A bootstrapping technique was used for internal validation. Results: The overall mortality within 6 months was 14.0%. Five independent predictors were identified, and a points system was constructed: age 75 years or older (2 points), coronary artery disease (2), cerebrovascular disease with hemiplegia (2), time of nephrology care before dialysis (<3.0 months [2]; ≥3 to <12 months [1]), and serum albumin levels (3.0-3.49 g/dL [1]; <3.0 g/dL [2]). A score of 6 identified patients with a 70% risk of 6-month mortality. Model performance was good in both discrimination (area under the curve of 0.793; [95% CI 0.73-0.86]) and validation (concordance statistics of 0.791 [95% CI 0.73-0.85]). Conclusions: We developed a simple prediction score based on readily available clinical and laboratory data that can be a practical and useful tool to assess short-term prognosis in elderly patients starting dialysis. It may help to inform patients and their families about ESRD treatment options and provide a more patient-centered overall approach to care.
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