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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.
- Regulation of erythropoietin production and recent trends in anaemia therapyPublication . Almeida, F.; Santos, S.; Beirão, I.About 30 years ago, the treatment of chronic renal disease anaemia was revolutionized by the introduction of recombinant human erythropoietin, which reduced the need for blood transfusions. In spite of this huge advance, the first recombinant human erythropoietin has a relatively short half-life and needs to be administered two to three times per week. Subsequently, other molecules were developed, such as darbepoetin alfa, continuous erythropoietin receptor activator (CERA) and peginesatide, with longer half-life, but the route of administration still remains a problem. Erythropoietin has an action that exceeds erythropoiesis and plays an important role in cell protection. Based on knowledge of the molecular mechanisms that control erythropoiesis, namely the regulation of EPO gene expression, through HIF system, GATA-2 and NF-kB, several upcoming therapeutic agents and strategies for stimulating and treating anaemia emerged. The main effort in developing these treatments is to achieve other routes of administration, more convenient for the patient, such as oral therapy, not disregarding an easier production, storage and frequency of administration. Some of them are still in laboratory phase and others already in clinical trials phase II or III. In this work, based on a literature search of studies using MEDLINE, our objective is to review the regulation of erythropoietin production and its functions, as well as treatment approach for anaemia of chronic kidney disease, with particular focus on new therapies
- Pancreas-kidney transplantation: clinical, metabolic and immunological outcomesPublication . Martins, L.; Castro-Henriques, A.
- 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
- Mesalazine induced tubulointersticial nephritisPublication . Campos, A.; Santos, S.; Santos, J.; Malheiro, J.; Lobato, L.; Vizcaíno, J.; Cabrita, A.Inflammatory bowel disease and its various treatments may affect the kidney in several ways tubulointersticial nephritis is a rare but serious complication of longer-term mesalazine use. There are few cases reported in the literature. We report the first two cases of mesalazine-induced tubulointersticial nephritis, recently diagnosed in our department. The first one refers to a patient with ulcerous colitis and the second one to a patient with Crohn’s disease. Then the authors present a review of literature about the renal involvement in the inflammatory bowel disease. New cases of mesalazine nephrotoxicity should be reported to allow more accurate incidence estimation of this serious adverse effect. Routine monitoring of renal function is simple, inexpensive and allows an early diagnosis of this complication
- Peritoneal dialysis dropouts in different age and era cohorts: focus on the elderlyPublication . Campos, A.; Malheiro, J.; Teixeira, L.; Carvalho, M.; Cabrita, A.; Rodrigues, A.Introduction and Aims: Peritoneal dialysis (PD) is an efficient renal replacement therapy (RRT), but still remains underutilized at any age. Clinicians fear the rate of dropouts and lower technique survival, particularly in elderly patients. The authors aimed to explore such outcomes over the past 3 decades, in different age and era cohorts. Methods: Consecutive incident patients starting PD were identified from an ongoing registry-base prospective study of quality assessment. In order to control for an era effect, patients were assigned to 6 cohorts (5 years interval) according to the admission year between 1985 and 2014. Regression models taking competing risks into account were performed to identify potential prognostic factors for death and transfer to haemodialysis (HD) (adjusted for age, gender, diabetes, cohort era, automated peritoneal dialysis (APD) use, and first treatment modality – PD first, PD after HD, PD after renal transplant (RT). Then the patients were studied according to age at enrolment in the programme: A (18 44 years; n = 193); B (45 64 years; n = 176) and C (≥ 65 years old; n = 75). The HD transfer rates using Poisson analysis were evaluated. The incidence of dropout rates was compared at different times and between age groups, focusing particular attention on the elderly. Results: A total of 525 patients were evaluated: 211 male (40.2%), aged 48 ± 15.7 years old, on PD for 23 (IQR 9 – 41.5) months. The major cause of dropout technique was transfer to HD (35.4%), followed by renal transplantation (27.6%) and death (21.7%). The probability of technical failure and renal transplantation at 2 and 5 years was 19.2% and 18.1% and 34.2%; 27.4%, respectively. Probability of death at 2 and 5 years was 12.7%, and 21.8%, respectively. The contemporary cohort was associated with a lower risk of mortality and lower risk of transfer to haemodialysis, with greater access to renal transplantation. The regression model Fine & Gray showed that older age was associated with increased mortality, but was not associated with greater technical failure. Transfer to HD occurred in the elderly at a rate of 11epy/100 patient year (in comparison to 15 and 14 epy/100 patient-year in non-elderly groups A and B, respectively P= 0.33). The proportions of specific causes of technique failure did not change significantly according to age cohort. The dropout rates due to access-related-infection and ultrafiltration failure decreased in the elderly group in the more contemporary cohort, despite the differences were not statistically significant. Conclusions: The dropout by technique failure decreased significantly in the recent decade. Age at admission in peritoneal dialysis did not show to be a compromising factor of the technique survival
- Acute kidney injury with active urinary sediment analysis, a positive ANCA test and hypocomplememtemia: A tough situationPublication . Campos, A.; Vizcaíno, J.; Coelho, A.; Freitas, C.; Rocha, G.
- 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.
- 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.