SNU - Sistema Nefro-urogenital (Doenças renais e urogenitais)
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Browsing SNU - Sistema Nefro-urogenital (Doenças renais e urogenitais) by Author "Almeida, M."
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- Impact of pre-transplant anti-MICA sensitization in graft rejection and survivalPublication . Costa, R.; Malheiro, J.; Tafulo, S.; Santos, C.; Almeida, M.; Pedroso, S.; Martins, L.; Dias, L.; Castro-Henriques, A.Background: Evidence supporting deleterious effect of preformed major histocompatibility class I chain-related A (MICA) antibodies in rejection incidence and graft survival is still unclear. Methods: Retrospective analysis of 554 kidney transplanted patients. Comparison between positive or negative for MICA antibodies patients was performed to characterize sensitizing triggers. Further classification according to pre-transplant flow cytometry-recorded anti–MICA and/or anti-human leukocyte antigen (HLA) antibodies was made to determine first year rejection incidence and graft survival. Multivariate analysis was applied to determine predictors for acute rejection. Results: Pre-formed anti-MICA antibodies were detected in 41 patients (7.4%). HLA sensitization, blood transfusions and pregnancies were frequently found in anti-MICA+ patients but only pre-formed anti-HLA class I antibodies showed independent association (OR 2.67, p= 0.02). Comparing to MICA-/HLA–, MICA-/HLA+ group presented significantly lower first year rejection-free survival (78.6% vs. 89.3%, p< 0.01), mostly occurred in the first six months, while no difference was found in MICA+/HLA– (88.9% vs. 89.3%, p= ns). MICA-/HLA+ showed independent impact in rejection (OR 2.09, p= 0.03), while no evidence was found in MICA+/HLA- (OR 1.08, p= ns). At 4 years, MICA-/HLA+ group presented lower graft survival (85.8% vs. 95.3%, p= 0.03). Again, no difference was found in MICA+/HLA- group (95.1% vs. 95.3%, p= ns). Conclusion: Our results do not support HLA-independent deleterious pathogenic role of pre-formed MICA antibodies on first year rejection incidence and graft survival.
- 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.
- 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.
- Pericardial and pleural effusions associated with sirolimus and discussion of possible mechanismsPublication . Rocha, S.; Pedroso, S.; Almeida, M.; Dias, L.; Martins, L.; Castro-Henriques, A.; Cabrita, A.Sirolimus, a mammalian target of rapamycin inhibitor, is an increasingly used immunosuppressant in solid-organ transplantation. There are an increasing number of reports of unusual oedematous adverse effects associated with this drug, including lymphoedema, ascites and pleural effusions, and a few reports of pericardial effusions. No pathophysiological explanation for these phenomena has been disclosed. We report a 33-year-old sirolimus-treated kidney transplant recipient with chronic pericardial and pleural effusions identified nine years after transplantation. He was initially treated for a presumed tuberculous pericarditis, even though cultures for Mycobacterium tuberculosis were negative. After 12 months of antitubercular therapy, visceral effusions persisted. Pericardial effusion was drained and stabilised. After exclusion of other causes, sirolimus toxicity was considered the most likely cause. Two months after discontinuation of sirolimus, visceraleffusions disappeared. Interaction of mammalian target of rapamycin inhibitors with mediators of lymphangiogenesis may be a common link in oedematous states associated with sirolimus.
- 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.
- Tacrolimus, a forgotten agent in kidney transplant leukopeniaPublication . Azevedo, P.; Freitas, C.; Silva, H.; Aguiar, P.; Santos, T.; Cabral, J.; Rocha, G.; Almeida, M.; Pedroso, S.; Martins, L.; Dias, L.; Castro-Henriques, A.; Cabrita, A.Leukopenia in kidney transplant patients is frequent, it causes potentially life-threatening complications, but it is often poorly characterized. Opportunistic infections, immunologic disturbances and drug-related toxicity are principal causes of single or multilineage cytopenias. Tacrolimus-induced leukopenia is a less recognized but frequent complication. We describe one patient with leukopenia developing within seven months after renal transplant. After excluding other potential causes, tacrolimus was switched to cyclosporine, with recovery of white blood cell count. Based on the clinical report, the authors reviewed causes of post-transplant leukopenia, focusing on the diagnostic investigation. Early diagnosis and interventions are fundamental to improve prognosis.
- The first ABO-incompatible kidney transplantation performed in PortugalPublication . Barreto, P.; Vieira, P.; Dias, L.; Almeida, M.; Pedroso, S.; Martins, L.; Castro-Henriques, A.; Bini, M.; Cabrita, A.Kidney transplantation is the optimal treatment of end-stage renal disease (ESRD) improving survival and quality of life for most recipients. In our country, potential living donors have been refused due to the ABO incompatibility barrier. However, ABO -incompatible living donor kidney transplant is presently common practice in several countries with good outcomes. The authors describe a case of a 49-year-old female patient, with chronic kidney disease due to autosomal dominant polycystic kidney disease, who had started haemodialysis 10 months before and with blood group O. The living donor was a 53-year-old sister with blood group B. The desensitization protocol was based on rituximab and plasmapheresis. The induction protocol used was basiliximab, tacrolimus, mofetil mycophenolate and metilprednisolone. Five days post -transplant she presented a normal graft function that remained during the eight months follow -up. This case reveals the first ABO incompatible living donor kidney transplant performed in Portugal with excellent outcome