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- Association of the Calcification Score of the Abdominal Aorta, Common Iliac, and Renal Arteries with Outcomes in Living Kidney DonorsPublication . Ribeiro, Luís Costa; Almeida, Manuela; J, Malheiro; Silva, Filipa; Nunes-Carneiro, Diogo; Martins, La Salete; Pedroso, Sofia; Silva-Ramos, MiguelBackground: Vascular calcification is an ever-more-common finding in protocoled pre-transplant imaging in living kidney donors. We intended to explore whether a connection could be found between the Agatston calcification score, prior to kidney donation, and post-donation renal function. Methods: This is a retrospective analysis of 156 living kidney donors who underwent living donor nephrectomy between January 2010 and December 2016. We quantified the total calcification score (TCaScore) by calculating the Agatston score for each vessel, abdominal aorta, common iliac, and renal arteries. Donors were placed into two different groups based on their TCaScore: <100 TCaScore group and ≥100 TCaScore group. The relationship between TCaScore, 1-year eGFR, proteinuria, and risk of 1 measurement of decreased renal function (eGFR < 60 mL/min/1.73 m2) over 5 years of follow-up was investigated. Results: The ≥100 TCaScore group consisted of 29 (19%) donors, with a median (interquartile range) calcification score of 164 (117-358). This group was significantly older, 56.7 ± 6.9 vs. 45.5 ± 10.6 (p < 0.001), had a higher average BMI (p < 0.019), and had a lower preoperative eGFR (p < 0.014). The 1-year eGFR was similarly diminished, 69.9 ± 15.7 vs. 76.3 ± 15.5 (p < 0.048), while also having an increased risk of decreased renal function during the follow-up, 22% vs. 48% (p < 0.007). Conclusions: Our study, through univariate analyses, found a relationship between a TCaScore > 100, lower 1-year eGFR, and decreased renal function in 5 years. However, a higher-than-expected vascular calcification should not be an excluding factor in donors, although they may require closer monitoring during follow-up.
- 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.
- 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.
- TRANSPLANTE DE RIM E PÂNCREAS: AUTOIMUNIDADEPublication . Martins, La Salete
- Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus.Publication . PEDROSO, S.L.; Martins, La Salete; SOUSA, S.; REIS, A.; DIAS, L.; HENRIQUES, A.C.; SARMENTO, A.M.; CABRITA, A.Transpl Int. 2007 Mar;20(3):291-6. Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus. Pedroso SL, Martins LS, Sousa S, Reis A, Dias L, Henriques AC, Sarmento AM, Cabrita A. Nephrology Department, Hospital Geral de Santo António, Porto, Portugal. sofiapedroso@sapo.pt Abstract The aim of our paper is to describe an unusual pulmonary toxicity of sirolimus (SRL) in a kidney transplant recipient. We present a 34-year-old woman with a second renal transplantation, complicated with steroid-resistant acute rejection and chronic allograft dysfunction. Two years after initiating SRL, she presented complaints of progressive dyspnoea, nonproductive cough, chest pain and low-grade fever of 1 month duration. She had chronic allograft nephropathy and slight elevation of lactic dehydrogenase levels. After exclusion of common reasons of this condition, a computed tomography (CT) of the thorax and bronchoscopy was performed, revealing ground-glass opacification with polygonal shapes on CT and an opaque appearance with numerous macrophages on bronchoalveolar lavage. The alveolar macrophages stained positive by Periodic acid-Schiff. Diagnosis of pulmonary alveolar proteinosis (PAP) was made and drug-induced toxicity was suspected. SRL was withdrawn with marked improvement in the patients' clinical and radiological status. PAP resolved within 3 months without further therapy. PAP is a very rare complication of SRL therapy with only a few cases described. Withdrawal of SRL with conversion to another immunosuppressant seems to be an appropriate procedure in this condition. PMID: 17291222 [PubMed - indexed for MEDLINE
- Transplantação renal pediátrica: experiência de um centroPublication . Nascimento, João; Rocha, Liliana; Faria, Maria Sameiro; Matos, Paula; Costa, Teresa; Martins, La Salete; Almeida, Manuela; Dias, Leonídio; Mota, Conceição; Henriques, A. CastroIntrodução: A insuficiência renal crónica terminal está associada a numerosas comorbilidades e a um aumento do risco de mortalidade cerca de 30 vezes superior à população pediátrica geral. O primeiro transplante renal bem sucedido em crianças foi realizado em 1954. Os progressos cirúrgicos e as novas terapêuticas imunossupressoras aumentaram a sobrevida dos doentes e do enxerto renal nos últimos anos. Objetivos: Avaliação da experiência em transplantação renal em idade pediátrica do Centro Hospitalar do Porto nos últimos 30 anos. Métodos: Estudo retrospetivo dos dados epidemiológicos e clínicos dos doentes pediátricos transplantados entre Janeiro de 1984 e Agosto 2013. Foi feita a análise da evolução tempo- real da atividade de transplantação através da comparação da sobrevida do enxerto por décadas de transplantação (1984-89 / 1990-99 / 2000-09 / 2010-13). Foi também comparada a sobre- vida do enxerto em dois grupos etários (0-10 anos ; 11-17 anos) à data da transplantação. Resultados: Cento e trinta e nove doentes (58.3% - sexo masculino) foram submetidos a 147 transplantes renais (6.8% de dador vivo). As anomalias congénitas do rim e trato urinário (56.5%) e as glomerulonefrites (18.4%) foram as causas principais de insuficiência renal. A sobrevida do enxerto não censurada aos 5, 10, 15 e 20 anos foi 84.7%, 71.1%, 60.0% e 51.0% e a sobrevida do doente aos 5, 10, 15 e 20 anos foi 97.9%, 95.9%, 94.7% e 94.7%, respetivamente. A sobrevida do enxerto aumentou ao longo do tempo e a diferença entre as décadas foi estatisticamente significativa (p=0.004). Apesar da melhor sobrevida no grupo com idade superior a 11 anos, a diferença da sobrevida do enxerto entre os grupos etários não foi estatisticamente significativa (p=0.697). Conclusão: Os resultados do Centro Hospitalar do Porto são comparáveis aos dos grandes centros de transplantação renal pediátrica. Observou-se uma melhoria dos resultados ao longo dos anos na nossa Unidade. A existência de um rigoroso processo de acompanhamento poderá ter ajudado a minimizar o impacto negativo da adolescência na sobrevida do enxerto.
- CT volumetry performs better than nuclear renography in predicting estimated renal function one year after living donationPublication . Almeida, Manuela; Pereira, Pedro R.; Ramos, Miguel; Nunes-Carneiro, Diogo; Mandaleno, Mariana; Silva, Filipa; Pedroso, Sofia; França, Manuela; Martins, La Salete; J, MalheiroThe evaluation of split renal function (SRF) is a critical issue in living kidney donations and can be evaluated using nuclear renography (NR) or computerized tomography (CT), with unclear comparative advantages. We conducted this retrospective study in 193 donors to examine the correlation of SRF assessed by NR and CT volumetry and compared their ability to predict remaining donor renal function at 1 year, through multiple approaches. A weak correlation between imaging techniques for evaluating the percentage of the remaining kidney volume was found in the global cohort, with an R2 = 0.15. However, the Bland-Altman plot showed an acceptable agreement (95% of the difference between techniques falling within - 8.51 to 6.11%). The predicted and observed eGFR one year after donation were calculated using the CKD-EPI, and CG/BSA equations. CT volume showed a better correlation than NR for both formulas (adjusted R2 of 0.42. and 0.61 vs 0.37 and 0.61 for CKD-EPI and CG/ BSA equations, respectively). In non-nested modeling tests, CT volumetry was significantly superior to NR for both equations. CT volumetry performed better than NR in predicting the estimated renal function of living donors at 1-year, independently from the eGFR equation.
- Medical Challenges of a Common Variable Immunodeficiency With a TNFRSF13B Gene Mutation in a Simultaneous Kidney and Pancreas Transplant RecipientPublication . Coimbra, Miguel T; Silvano, José; Martins, La SaleteCommon variable immune deficiency (CVID) is a primary immunodeficiency disorder, with hypogammaglobulinemia and increased susceptibility to recurrent infections, autoimmune disorders, granulomatous diseases and malignancy. Among the solid organ transplant (SOT) recipient population, those with primary immunodeficiency disorders under chronic immunosuppression therapy can theoretically be at higher risk of atypical infections, autoimmune complications and disease recurrence with suboptimal long term graft survival, but literature is scarce. Here, we report a 27-year-old female with type 1 diabetes mellitus, complicated with nephropathy that progressed to end-stage renal disease (ESRD), who had a history of a chronic inflammatory response dysregulation, with chronic monoarthritis, persistent elevation of inflammation markers, recurrent infections, low immunoglobulin G (IgG) and A (IgA) serum levels, a slightly decreased population of memory B cells at flow cytometric immunophenotyping, and a confirmed pathological heterozygous mutation in the tumor necrosis factor receptor superfamily 13B (TNFRSF13B), with a suspected diagnosis of CVID. Whilst on hemodialysis, she received a simultaneous kidney and pancreas transplant from a standard criteria donor (SCD), and our induction and maintenance immunosuppression protocol and prophylaxis regimen allowed for a successful transplant with immediate pancreatic function, with no evidence of renal graft rejection upon biopsy in the early post-transplant period, and no novel episodes of serious infectious complications were recorded during a follow-up period of six months