Abstract Introduction: Kidney transplant (KT) recipients have a high risk for adverse outcomes from infections, such as COVID-19. Methods: We have retrospectively reviewed all KT recipients with documented COVID-19 between March 1, 2020, and March 15, 2021, and analyzed patients’ characteristics, clinical course, treatment, and outcomes. Results: We identified 123 patients, 72% were male, with a mean age of 54.5±13.0 years. Twenty percent were asymptomatic, 7% had a nosocomial transmission, and 36% of the remainder required hospitalization. Almost all admitted patients received oxygen, 30% required invasive mechanical ventilation (IMV), more than a half had acute kidney injury, with 10% requiring dialysis, and 20% died. Incidence was comparable to that of the Portuguese population, but the mortality rate was almost four times higher (SMR of 3.768 (95% CI:1.723-7.154). Higher body mass index (OR 1.275, P=0.001), lower baseline graft function (OR 0.968, P=0.015), and nosocomial transmission (OR 13.836, P=0.019) were associated with oxygen demand, whereas female gender (OR 3.801, P=0.031) and lower baseline kidney graft function (OR 0.955, P=0.005), but not body mass index, were associated with IMV and/or death. Conclusion: Mortality rate in KT patients was higher than in the general population and lower baseline kidney function was the most consistent marker for adverse outcomes.

Resumo Introdução: Os receptores de transplante renal (TR) apresentam um alto risco para desfechos adversos de infecções, tais como a COVID-19. Métodos: Revisamos retrospectivamente todos os receptores de TR com COVID-19 documentada entre 1º de Março de 2020 e 15 de Março de 2021, e analisamos as características, curso clínico, tratamento e desfechos dos pacientes. Resultados: Identificamos 123 pacientes, 72% do sexo masculino, com uma média de idade de 54,5±13,0 anos. Vinte por cento eram assintomáticos, 7% apresentaram transmissão nosocomial, e 36% do restante necessitaram de internação. Quase todos os pacientes internados receberam oxigênio, 30% necessitaram de ventilação mecânica invasiva (VMI), mais da metade apresentou lesão renal aguda, com 10% necessitando de diálise, e 20% foram a óbito. A incidência foi comparável à da população portuguesa, mas a taxa de mortalidade foi quase quatro vezes superior (TMP de 3,768 (IC 95%: 1,723-7,154). Maior índice de massa corporal (OR 1,275; P=0,001), menor função do enxerto basal (OR 0,968; P=0,015), e transmissão nosocomial (OR 13,836; P=0,019) foram associados à demanda de oxigênio, enquanto sexo feminino (OR 3,801; P=0,031) e menor função do enxerto renal basal (OR 0,955; P=0,005), mas não índice de massa corporal, foram associados à VMI e/ou óbito. Conclusão: A taxa de mortalidade em pacientes com TR foi mais elevada do que na população em geral e a função renal basal mais baixa foi o marcador mais consistente para desfechos adversos.

Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody that has been associated with delayed pulmonary toxicity. In patients receiving RTX, hypersensitivity pneumonitis, although rare, should be considered in the appropriate clinical and radiographic setting. The authors present a case of hypersensitivity pneumonitis associated with a single dose of RTX treatment in a kidney transplanted patient with acute antibody-mediated rejection.

Introduction: ABO incompatibility was considered a barrier to kidney transplant. However, the shortage of available organs for transplantation and the excellent long-term results further establish ABO-incompatible (ABOi) as a safe and effective therapeutic strategy. The aim of the present study was to evaluate the outcomes of ABOi transplantation in terms of graft survival and function, rejection episodes and infections complications. Methods: The authors present a single-center retrospective observational study in a unit with approximately 370 living donor kidney transplants registered. This study includes the analysis of 12 patients who underwent ABOi living donor kidney transplantation between November 2014 and July 2019. Desensitization protocol consisted of intravenous Rituximab 375mg/m2 single dose administration 2 weeks pretransplant. Tacrolimus and Mycophenolate Mofetil were started before transplantation one week and 48 hours respectively. Plasmapheresis was performed to remove anti-A or B antibodies until their titers were <1:8 during the first post-operative week and <1:16 at the second. All kidney recipients of both ABOi grafts received Basiliximab (20mg on days 0 and 4) as antibody induction therapy. Maintenance immunosuppression consisted of Tacrolimus, Mycophenolate Mofetil and corticosteroid. Results: A total of 12 patients were included in the study, 75% male; 43 years (IQR 31-50). The most common blood group mismatch was A to O (n=4; 33%). In the first year, 2 of patients (25%) developed acute rejection. The follow-up time was 17 months (IQR 7-36). Five patients (42%) developed infectious complications. None patients developed cytomegalovirus or BK polyomavirus infections. At the end graft and patient survival were 100%. Conclusion: ABOi kidney transplantation has become a routine procedure. With this approach, about 30% of living donors who were refused in the past can now donate their kidneys and thereby significantly expand the living donor pool. The immunosuppressive protocol of this unit can be considered safe.

We report a patient who had received a first kidney transplant and had preformed DSA anti-HLA-Cw, developing AMR C4d+ soon after transplant. Classically anti-HLA-Cw are considered less immunogenic and are not considered in many organ allocation systems or immunologic risk stratification algorithms, including in Portugal. However, data from literature confirms that their presence is as deleterious as DSA anti-HLA A/B/DR/DQ. Thus we should take HLA-C typing and respective antibody identification into account in sensitized patients, in order to access risk stratification and establish the need for correct induction or desensitization therapies

Over the last 15 years, better immunosuppressive drugs have decreased acute rejection rates in kidney transplantation but have also led to an increase in the incidence and impact of BK virus nephropathy. The authors report the case of a 62--year-old man submitted to a renal transplant of a deceased donor with an immunosuppression regimen free of rabbit anti -thymocyte globulin and tacrolimus, in whom BK nephropathy was diagnosed at seven weeks post-transplant. Intravenous human immunoglobulin (IVIG) was administered after immunosuppression reduction. Instituted treatment was successful. This clinical case highlights the importance of a high index of suspicion for an atypical presentation of BK nephropathy in renal transplant recipients and strengthens the need for other therapeutic interventions beyond the reduction of immunosuppression. It was the starting point for a review of BK virus nephropathy in kidney transplantation with a focus on risk factors, diagnosis and treatment

Introduction: Kidney transplant improves survival even in highly-sensitized(HS) patients. To overcome their disadvantage in accessing transplantation, those with high Complement Dependent Cytotoxic PRA (CDC-PRA) receive additional points during allocation. Whether this strategy reaches all HS patients and how long they wait for a transplant is largely undetermined. Methods: Patients on our unit’s active wait-list for kidney transplantation in the year 2014 were analyzed. CDC-PRA and calculated PRA (cPRA) were recorded. To obtain cPRA, antibodies in the last serum available specific for HLA-A,-B or -DR with an intensity > 1000 MFI were considered. Results: The cPRA values in the population (N=551) were 0% (N=312), 1-79% (N=118) and ≥ 80% (22%; N=121). Among these groups, the proportion of women (29.5, 55.9 and 61.2%, P<0.001), prior sensitizing events (43.3, 80.5 and 96.7%, P<0.001) and time on dialysis (median of 3.9, 4.1 and 6.0 years, P<0.001) increased with cPRA, respectively. In most of those with a cPRA ≥ 80%, the CDC-PRA raised no suspicion of HS status (median 0%, P25-75 0-8%) and only 35 (28.9%) or 12 patients (9.9%) had a CDC-PRA in the peak serum higher than 50 or 80%, respectively (cut-offs needed to obtain additional points during allocation). HS patients by cPRA corresponded to 71% vs 15% of patients waiting for ≥ or <8 years, respectively (P<0.001). Even after exclusion of patients with a CDC-PRA above 50%, this disproportionate representation remained (58% versus 13%, P<0.001). Conclusion: HS patients as measured by cPRA remained longer on the wait-list, both in the primary analysis and when excluding those with a CDC-PRA> 50%. Moreover, only 30% of HS by cPRA patients received the extra points designed to improve their transplantability. We consider that both CDC-PRA and cPRA should be taken into account when defining HS status

Introduction: Malignancy management in renal transplant recipients is becoming a major factor affecting long-term patient survival. Thus, we intended to evaluate both incidence and prognosis of malignant diseases following renal transplantation at a single centre in Portugal. Methods: We studied retrospectively the 2,358 patients who underwent kidney transplantation (KT) between 1983 and 2014. Apart from descriptive analysis, both demographic and clinical characteristics of cancer and non-cancer cancer patients were compared. Results: During a median follow-up of 118 (IQR 57-179) months, 139 patients (5.8%) developed 158 de novo malignancies, with a median time from KT to diagnosis of 76..5 (IQR 21.0-132.0) months. When compared to non-cancer patients, they were older at KT date, had longer graft survival and a lower living donor recipients’ prevalence. As for post-transplant malignancies analysis, the most common were non-cutaneous non-lymphomatous cancers (49.4%, n=78), skin cancers (35.4%, n=56) and post-transplant lymphoproliferative disorders (9.5%, n=15). Considering specific diagnosis, squamous cell carcinoma and basal cell carcinoma with 17.1% and 16.5% respectively, and non-Hodgkin lymphomas with 7.6%, were the most frequent. Global mortality among cancer patients was 36.0%, with a median time of 9.7 (IQR 1.9-17.5) months from time of diagnosis to death. As for survival analysis, cancer patient survival was significantly lower while censored graft survival was significantly higher in this group. Conclusion: Incidence and characteristics of malignancy following renal transplantation in our unit are similar to those globally described, despite some traits probably a result of specific ethnic and environmental characteristics

Introdução: 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. Objectivos: 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 temporal 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 sobrevida 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.

Introduction: End-stage renal disease in children is associated with numerous comorbidities and with age-specific mortality rates approximately 30 times higher than in healthy children. The first kidney transplantation in children was performed successfully in 1954. Surgical advances and new immunosuppressive medications have greatly improved patient’s and graft’s survival in the last years. Aim: Report Centro Hospitalar do Porto experience in pediatric renal transplantation in the last 30 years. Methods: Epidemiological and clinical data of all patients younger than 18 years, transplanted between January 1984 and August 2013, were collected from our database. In order to analyze the transplantation outcome in our center we compare graft survival between decades (1984-89 / 1990-99 / 2000-09 / 2010-13). We also compare graft survival between two age groups of patients (0-10 years ; 11-17 years) at the time of surgery. Results: One hundred thirty-nine patients (58.3% male) underwent 147 renal transplants (6.8% live donors). Congenital anomalies of the kidney and urinary tract (56.5%) and glomerulonephritis (18.4%) were the major causes of renal disease. Uncensored graft survivals rates at 5, 10, 15 and 20 years were 84.7%, 71.1%, 60.0% and 51.0%, while patient survivals were 97.9%, 95.9%, 94.7% and 94.7% respectively. Graft survival improved over time and the difference between the decades was statistically significant (p=0.004). Despite the better survival in the group of patients older than 11 years, graft’s survival difference between the two age groups was not statistically significant (p=0.697). Conclusion: The results of our hospital are comparable to other international centers. Significant improvement in survival was observed over the time. It seems that an accurate follow-up of our patients helps to minimize the negative impact of adolescence on graft survival rates.

Introdução: O efeito deletério dos anticorpos para antigénios MICA (major histocompatibility class I chainrelated A) na incidência de rejeição aguda e sobrevida do enxerto ainda não está consensualmente estabelecido. Metódos: Estudo retrospetivo de 554 transplantados renais. A análise comparativa entre doentes positivos e negativos para anticorpos anti-MICA pré-formados foi realizada para avaliar eventos sensibilizadores. A incidência de rejeição aguda no primeiro ano pós transplante renal e a sobrevida do enxerto renal foram determinadas consoante o resultado da citometria de fluxo pré-transplante para anticorpos anti-MICA e/ou anti- HLA (anti-human leukocyte antigen). Aplicou-se um modelo de análise multivariada para identificação de preditores independentes para rejeição aguda. Resultados: Foram identificados 41 doentes (7.4%) com anticorpos anti-MICA pré formados. A sensibilização para HLA, as transfusões sanguíneas e gestações prévias foram mais frequentes nos doentes MICA + mas apenas a presença de anticorpos anti-HLA classe I apresentou uma associação independente (OR 2.67, p = 0.02). Comparativamente ao grupo MICA-/HLA-, o grupo MICA-/HLA+ apresentou menor sobrevida livre de rejeição ao 1º ano (78.6% vs. 89.3%, p < 0.01), maioritariamente ocorrida nos primeiros seis meses, enquanto que nenhuma diferença foi encontrada com o grupo MICA+/HLA- (88.9% vs. 89.3%, p = ns). Apenas o status MICA-/HLA+ teve impacto independente na incidência de rejeição (OR 2.09, p = 0.03), ao contrário do status MICA+/HLA- (OR 1.08, p = ns). O grupo MICA-/HLA+ apresentou menor sobrevida do enxerto censurada para a morte aos 4 anos (85.8% vs. 95.3%, p = 0.03), não se verificando diferenças no grupo MICA+/HLA- (95.1% vs. 95.3%, p = ns). Conclusão: Os nossos resultados não suportam um efeito deletério dos anticorpos pré-formados para MICA, independente da sensibilização HLA, na incidência de rejeição aguda no 1º ano pós transplante e na sobrevida do enxerto

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

A leucopenia no doente transplantado renal é comum, causa complicações com potencial risco de vida, mas é muitas vezes mal caracterizada. As infecções por agentes oportunistas, distúrbios imunológicos e toxicidade secundária a fármacos são as principais causas de citopenias de uma ou várias linhas. A leucopenia induzida pelo tacrolimus é uma complicação frequente, mas pouco reconhecida. Descrevemos um doente com início de leucopenia sete meses pós-transplante renal. Após excluir outras potenciais causas, o tacrolimus foi substituído pela ciclosporina, com recuperação da contagem leucocitária. Baseado no caso clínico, os autores fizeram uma revisão das causas de leucopenia pós-transplante e sua investigação. O diagnóstico e tratamento precoces são fundamentais na melhoria do prognóstico.

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.

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, visceral effusions disappeared. Interaction of mammalian target of rapamycin inhibitors with mediators of lymphangiogenesis may be a common link in oedematous states associated with sirolimus.