ABSTRACT Pneumocystis jirovecii (PJ) opportunistic infections occur in immunocompromised patients impacting significantly hospitalizations and mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) is universally used as prophylaxis of Pneumocystis jirovecii pneumonia (PJP) and therefore, this infection is rare condition in solid organ transplant (SOT) recipients. We present a case of a 46-years-old male, who received an ABO-incompatible transplant with prior desensitization protocol with plasmapheresis, rituximab, and anti-CMV immunoglobulin. IgG anti-B title pre-desensitization was 1:128. The patient had 6 ABDR mismatches, without HLA antibodies, and the CDC crossmatch for T and B cells was negative. Both recipient and donor were CMV positive (D+/R+). The patient received induction immunosuppression with corticosteroids, basiliximab, calcineurin inhibitor, and mycophenolate mofetil. Immediate kidney function was verified, and three additional plasmapheresis sessions were performed. At discharge serum creatinine (sCr) was 1.38 mg/dL, but kidney function declined during the first 6 months (sCr 2.5 mg/dL). Urinalysis was unremarkable. A kidney biopsy was declined by the patient. Unit protocol maintained the prophylaxis for PJP and cytomegalovirus (CMV) infection with TMP-SMX and valganciclovir. The patient was admitted to the emergency department 20 months after the transplant with respiratory symptoms and was diagnosed with PJP. Bronchoalveolar lavage fluid was also positive for CMV. Intensive care unit (ICU) admission was necessary due to clinical deterioration, with subsequent good evolution without mechanical ventilation. At discharge, prophylaxis with TMP-SMX and valganciclovir was maintained for more than six months. Here we discuss the late onset of PJP, and the main risk factors related to severe infection. Transplant subgroups in which longer PJP prophylaxis could be beneficial and the indication to re-start PJP prophylaxis is still under discussion.

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.

ABSTRACT Older to older living kidney transplantation is an acceptable alternative to avoid dialysis, improve quality of life and maintain favorable long-term outcomes of patients with end-stage kidney disease. However, the management of these patients is complex and the acceptance of older donors and recipients to kidney transplantation remains controversial. The older recipients usually have several comorbidities that may complicate the postoperative course and increase the risk of end-stage kidney disease. We present a clinical case of living kidney transplantation between an older donor and recipient, both over 70 years old, who evolved to a stage 3 chronic kidney disease, without proteinuria, hypertension, or other complications, three years after transplantation. Our case reinforces favorable outcomes in older living transplantation, both for recipient and donor, as has been demonstrated in several published studies.

Resumo A ocorrência de ascite no pós-Transplante Renal (TR) é infrequente, podendo ser consequência de complicações cirúrgicas ou médicas. Caso clínico: 61 anos, masculino, antecedentes de hipertensão arterial, carcinoma da língua e hábitos alcoólicos 12-20g/dia. Doença renal crônica secundária à doença renal poliquística autossômica dominante, sem poliquistose hepática. Submetido a TR de doador cadáver em setembro de 2017. Atraso na função de enxerto por estenose da artéria renal, corrigida cirurgicamente. Internado em janeiro de 2018 por ascite de novo, sem resposta a diuréticos. Circulação colateral abdominal visível. Disfunção do enxerto, tacrolinemia adequada. Sedimento urinário inocente. Anemia ligeira, sem trombocitopenia. Albumina sérica 4,0g/dL. Bioquímica hepática normal. Líquido peritoneal com características de transudado e gradiente sero-ascítico de albumina > 1,1. Ecografia com hepatomegalia, eixos vasculares permeáveis, sem esplenomegalia. Suspendeu micofenolato mofetil, reduziu restante imunossupressão. Manteve ascite refratária: excluídas etiologias infecciosas, metabólicas, autoimunes e neoplásicas. Sem proteinúria nefrótica e sem insuficiência cardíaca. RM: micronódulos compatíveis com quistos biliares. EDA sem varizes gastroesofágicas. Linfocintigrafia abdominal normal. Submetido a laparoscopia exploradora com biópsia hepática: cirrose septal incompleta de provável etiologia vascular, alguns ductos biliares dilatados. Manteve disfunção progressiva do TR, reiniciou hemodiálise. Proposta medição direta da pressão portal, protelada por resolução da ascite. Recuperação posterior da função de enxerto. Discussão: A cirrose septal incompleta é uma causa incomum de hipertensão portal não cirrótica. A sua definição é morfológica e a fisiopatologia, pouco conhecida. Não encontramos publicados casos de ascite pós-TR secundária a esta patologia, descrita como possivelmente associada a fármacos, alterações imunitárias, infecções, hipercoagulabilidade e predisposição genética.

Abstract The occurrence of ascites after Renal Transplant (RT) is infrequent, and may be a consequence of surgical or medical complications. Case report: 61 year-old, male, history of arterial hypertension, tongue carcinoma and alcoholic habits 12-20g/day. He had chronic kidney disease secondary to autosomal dominant polycystic kidney disease, without hepatic polycystic disease. He underwent cadaver donor RT in September 2017. He had delayed graft function by surgically corrected renal artery stenosis. He was admitted in January 2018 for ascites de novo, with no response to diuretics. HE had visible abdominal collateral circulation. Graft dysfunction, adequate tacrolinemia, Innocent urinary sediment, mild anemia, without thrombocytopenia. Serum albumin 4.0g / dL. Normal hepatic biochemistry. Peritoneal fluid with transudate characteristics and serum albumin gradient > 1.1. Ultrasound showed hepatomegaly, permeable vascular axes, without splenomegaly. Mycophenolate mofetil was suspended, with reduced remaining immunosuppression. He maintained refractory ascites: excluded infectious, metabolic, autoimmune and neoplastic etiologies. No nephrotic proteinuria and no heart failure. MRI: micronodules compatible with bile cysts. Upper Digestive Tract Endoscopy did not show gastroesophageal varicose veins. Normal abdominal lymphoscintigraphy. He underwent exploratory laparoscopy with liver biopsy: incomplete septal cirrhosis of probable vascular etiology some dilated bile ducts. He maintained progressive RT dysfunction and restarted hemodialysis. The proposed direct measurement of portal pressure was delayed by ascites resolution. There was further recovery of the graft function. Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition.

The passenger lymphocyte syndrome may cause hemolytic anemia after bone marrow and solid organ transplantation when there is minor erythrocyte antigen incompatibility in the donor/recipient pair. Anemia is usually self-limiting, frequently related to ABO antibodies and rarely to Rh mismatches. We report a rare case of passenger B lymphocyte syndrome mediated by Rh antibodies occurring after a donor living renal transplantation and discuss its clinical severity at presentation, the therapeutic decisions and their outcome.

Tubulointersticial nephritis and uveitis syndrome is an idiopathic and rare cause of acute kidney injury that should not overlooked, because it usually requires specific therapeutic interventions. We report two distinct cases: a young and an elder female. Both cases presented with unspecific constitutional symptoms but had different onset of renal and ocular involvement. Both were treated with topical and systemic corticoids and although there was a good initial response in both cases, an early relapse after steroids taper was observed in the younger patient and a persistent renal dysfunction in the older one. A high clinical suspicion and understanding of this disease is necessary for an adequate management and treatment of these patients. Recent data associates a worse renal prognosis when the disease appears inadvanced age. In both of our cases the outcome was good but we had a short follow-up. The histological presentation of this disease in our older patient was similar to that reported in the literature, with a high percentage of fibrosis and chronicity of renal tissue that can contribute to the higher grade of renal dysfunction in this type of patients

Monoclonal gammopathies are a heterogeneous group of disorders characterized by clonal proliferation of immunoglobulin produced by B-lymphocytes or plasma cell clone. The term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. Screening for monoclonal immunoglobulin and an appropriate hematologic workup are fundamental and sometimes a difficult challenge, with therapeutic and prognostic implications. Kidney biopsy is essential to determine the exact nature of the lesion and to evaluate the severity of renal disease. In this review we discuss the clinical and pathologic features of MGRS, highlighting the most diagnostic difficulties and current therapeutic options

Abstract Patients who are candidates for a second kidney transplant (SKT) frequently have a higher level of panel reactive antibodies (PRA). We assessed the allosensitisation change after a first graft failure (GF), its predictors and impact on retransplantat outcomes. We retrospectively selected 140 adult patients who received a SKT. Recipient and donor characteristics were analyzed. We defined the delta PRA (dPRA) as the difference between peak PRA before the SKT and first one (cohort median value = +10%). Logistic regression analysis was used to determine risk factors for dPRA ≥ 10% and acute rejection (AR) in the SKT. Univariable and multivariable Cox analysis was applied to assess independent predictors of second GF. Risk factors for dPRA ≥ 10% at SKT were AR (OR = 2.57; P = 0.022), first graft survival <1 year (OR = 2.47; P = 0.030) and ABDR HLA mismatch (OR = 1.38 per each mismatch; P = 0.038). AR in the SKT was associated with dPRA ≥ 10% (OR = 2.79; P = 0.047). Induction with a lymphocyte-depleting agent had a protective effect (OR = 0.23; P = 0.010). SKT survival was lower (P = 0.008) in patients with a dPRA ≥ 10% (75.6%, 60.5% in dPRA ≥ 10%; 88.6%, 88.6% in dPRA < 10% patients at 5 and 10 years, post-transplant respectively). Multivariable Cox regression showed that dPRA ≥ 10% (HR = 2.38, P = 0.042), delayed graft function (HR = 2.82, P = 0.006) and AR (HR = 3.30, P = 0.001) in the SKT were independent predictors of retransplant failure. This study shows that an increased allosensitisation at retransplant was associated with the degree of HLA mismatch and led to poorer outcomes. De-emphasis of HLA matching in current allocation policies may be undesirable, particularly in patients with a higher chance of needing a SKT.

Resumen Los pacientes candidatos a un segundo trasplante de riñón (STR) tienen a menudo un nivel superior de panel reactivo de anticuerpos (PRA). Evaluamos el cambio de alosensibilización después de un primer fracaso del injerto, sus predictores y repercusión en los resultados del retrasplante. Elegimos retrospectivamente a 140 pacientes adultos que recibieron un STR. Analizamos las características de los receptores y de los donantes. Definimos el delta PRA (dPRA) como la diferencia entre el pico de PRA antes del STR y el primero (cohorte mediana = +10%). Se aplicó análisis de regresión logística para determinar los factores de riesgo para dPRA ≥ 10% y rechazo agudo (RA) en STR y análisis univariado y multivariado de Cox para evaluar predictores independientes de fallo del retrasplante. Los factores de riesgo para dPRA ≥ 10% fueron: RA (OR = 2,57; p = 0,022), supervivencia del primero injerto menor a un año (OR = 2,47; p = 0,030) e incompatibilidad HLA ABDR (OR = 1,38 por cada mismatch; p = 0,038). El RA en el STR fue asociado con dPRA ≥ 10% (OR = 2,79; p = 0,047). La inducción con un agente depletor de linfocitos tuvo un efecto protector (OR = 0,23; p = 0,010). La supervivencia del STR fue menor en pacientes con dPRA ≥ 10% (75,6; 60,5% en dPRA ≥ 1 0%; y 88,6; 88,6% en dPRA < 10%; a los 5 y 10 años). La regresión multivariada de Cox mostró que dPRA ≥ 10% (HR = 2,38; p = 0,042), función retardada de injerto (HR = 2,82; p = 0.006) y RA (HR = 3,30; p = 0,001) en STR fueron factores predictores independientes de fracaso en el retrasplante. Este estudio muestra que un incremento en la alosensibilización de retrasplante se ha asociado con el grado de incompatibilidad HLA y puede conducir a resultados más pobres en STR. La falta de énfasis en la compatibilidad de HLA en las políticas actuales de asignación puede no ser deseable, especialmente en pacientes con una mayor probabilidad de necesitar un STR.

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: 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

O transplante renal é a modalidade de tratamento da doença renal crónica estadio 5 associada a melhores sobrevivência e qualidade de vida. No nosso país muitos potenciais dadores vivos têm sido recusados devido à incompatibilidade ABO. Contudo, o transplante renal de dador vivo ABO incompatível é hoje prática comum em diversos países com resultados positivos. Os autores descrevem o caso de doente do sexo feminino, de 49 anos, com doença renal crónica secundária a doença renal poliquística autossómica dominante, que havia iniciado hemodiálise 10 meses antes e com grupo sanguíneo O. O dador vivo foi uma irmã de 53 anos, grupo sanguíneo B. O protocolo de dessensibilização baseou-se em rituximab e plasmaferese. O protocolo de indução foi com basiliximab, tacrolimus, micofenolato de mofetil e metilprednisolona. Evoluiu com função normal do enxerto 5 dias pós -transplante que se manteve durante o follow -up de 8 meses. Este caso clinico ilustra o primeiro transplante renal de dador vivo ABO incompatível efectuado em Portugal com excelente resultado

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

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

Complicações infeciosas nos doentes transplantados renais são diversas e ocorrem quer por microrganismos habituais, quer por microrganismos oportunistas. Pneumocystis jiroveci, fungo oportunista, pode provocar pneumonia ameaçadora à vida nos doentes transplantados renais principalmente nos primeiros 6 meses após o transplante renal. Esta infeção pode ocorrer 1 ano após o transplante renal, mas a sua frequência é muito baixa. Elevada dose de imunossupressão, infeção por citomegalovirus, rejeição aguda e baixa taxa de filtração glomerular são fatores de risco para o desenvolvimento de pneumonia por pneumocystis nos doentes transplantados renais. O tratamento de escolha é realizado com doses elevadas de trimetoprim-sulfametoxazol, redução da dose de imunossupressão e em casos de severidade (definido: PaO2 < 70 mmHg ou gradiente arterio-alveolar > 35 mmHg), associação com esteroides é recomendada. Apresentamos o caso de pneumonia por pneumocystis jiroveci, 12,5 anos após o transplante renal. Doente do sexo masculino de 51 anos que recorreu ao hospital por astenia, febre e queixas geniturinárias com 3 dias de evolução. Apesar do tratamento inicial para a cistite ele manteve febre (> 38,5°C) e desenvolveu de novo tosse seca, hipoxemia e dispneia súbita. Ao exame físico a realçar taquicardia, cianose, sibilos e crepitações na auscultação pulmonar. Alterações radiográficas a demonstrar infiltrado intersticial bilateral (não presente aquando da admissão). Transferido ao 3º dia para a unidade de cuidados intensivos para início de ventilação não invasiva. O diagnóstico foi realizado pelo isolamento de pneumocystis no lavado broncoalveolar. O tratamento foi realizado com doses elevadas de trimetoprim-sulfametoxazol endovenoso em associação com corticoide com melhoria clínica. O diagnóstico adequado e a administração precoce de antibiótico foram os pontos-chave para o sucesso terapêutico, uma vez que esta patologia se associa a elevada taxa de mortalidade. Este diagnóstico não deverá ser esquecido

Potential aetiologies of infection in kidney transplant patients are diverse, ranging from common community-acquired infectious diseases to uncommon opportunistic infections. Pneumocystis is a wellknown opportunistic fungus that can cause life-threatening pneumonia in kidney transplant patients mostly within the first 6 months post-transplantation. This en tity may occur after one year post-transplant, but the rate is very low. High immunosuppression, cytomegalovirus infection, previous history of acute rejection and poor GFR are risk factors for the occurrence of pneumocystis pneumonia (PCP) in kidney transplant patients. The treatment of choice is high-dose trimethoprim-sulfamethoxazol (TMP-SMX), reduction of immunosuppressive therapy and, in severe cases (defined by PaO2 < 70 mmHg or an arterial-alveolar gradient > 35 mmHg), association with steroids. We report a case of PCP 12.5 years after renal transplant. A 51-yearold male presented to the hospital with a 3-day history of asthenia, fever and genitourinary complains. Despite the initial treatment for cystitis he kept fever (> 38.5°C) and developed dry cough, hypoxaemia and rapidly progressive dyspnea. Physical examination revealed increased respiratory rate, tachycardia, cyanosis, wheezing and crackles on pulmonary auscultation. Radiographic alterations showed a bilateral interstitial infiltrates (not present on admission). On the 3th day, he was transferred to the intensive care unit and started non-invasive ventilation. The diagnosis was established by the identification of Pneumocystis in bronchoalveolar lavage. Treatment was made with high-dose intravenous TMP-SMX plus steroids and resulted in clinical improvement of the symptoms and complaints. Early diagnosis and prompt administration of empiric antimicrobial therapy are the cornerstones of successful treatment since the disease is associated with high mortality rate. This diagnosis should never be forgotten.

A glomerulonefrite membranoproliferativa com crioglobulinemia associa-se frequentemente à infeção pelo vírus da hepatite C. O tratamento desta entidade não é consensual e representa um desafio para os clínicos. Apresentamos um caso de glomerulonefrite membranoproliferativa associada a crioglobulinemia tipo II num doente do sexo masculino de 46 anos portador de enxerto renal de dador cadavérico desde 2010. O seu valor de creatinina sérico (SCr) era 1,1 mg/dl. Após 3 anos do transplante o paciente apresentou-se com síndrome nefrítico em associação com agravamento da função renal (SCr - 2,1 mg/dl). Os exames laboratoriais demonstraram: fator reumatoide positivo, crioglobulinemia tipo II, hipocomplementemia. Os anticorpos antinuclear e anti-double stranded DNA foram negativos. Apesar da presença de anticorpos anti-HCV a carga vírica era indetectável. A biópsia do enxerto renal demonstrou lesões compatíveis com glomerulonefrite membranoproliferativa com depósitos granulares para IgM e C3 e marcação com C4d negativa na imunofluorescência. Iniciou terapêutica com pulsos de metilprednisolona seguido posteriormente por prednisolona oral em associação com rituximab. Dois meses após a última dose de Rituximab o valor de creatinina melhorou para 1,27 mg/dl, a proteinúria diminuiu e os níveis de C3 normalizaram. O doseamento de crioglobulinas e de fator reumatoide foi negativo e a carga vírica do VHC permaneceu indetectável. Foi perdido o follow-up do doente. No nosso caso o tratamento com Rituximab associou-se a uma melhoria clínica. Um período de follow-up maior é necessário para a monitorização clínica uma vez que as taxas de recidiva são elevadas de acordo com estudos publicados na literatura.

The most common HCV-related nephropathy is glomerulonephritis (MPGN), usually in the context of cryoglobulinaemia. The treatment of this entity is not consensual and represents a challenge to clinicians. We report a case of membranoproliferative glomerulonephritis associated with type II in a 46-year-old Caucasian male recipient of a deceased kidney transplant in 2010. His baseline serum creatinine (SCr) was 1.1 mg/dl. After three years post-transplantation, he presented with nephritic syndrome in association with renal function impairment (SCr - 2.1 mg/dl). The laboratory tests revealed positive rheumatoid factor, hypocomplementaemia and a positive cryocrit with type II cryoglobulinaemia. Antinuclear autoantibodies and anti-double stranded DNA antibodies were negative. Despite the presence of anti-HCV antibodies, the viral load remained undetectable. The allograft biopsy showed lesions compatible with membranoproliferative , with staining in the immunofluorescence for granular IgM and C3 and no C4d. He was treated with methylprednisolone pulses followed by oral prednisolone in association with rituximab. Two months after the last dose of rituximab, the SCr improved to 1.27 mg/dl, the proteinuria decreased and serum C3 levels normalized. Cryogloglobulins and rheumatoid factor became negative and HCV RNA remained undetectable. The patient was lost for follow-up. In our case, the treatment with rituximab resulted in a favourable outcome, although a longer follow-up period may be needed to evaluate the clinical response, since other studies reported high relapse rates.

Objetivo: Avaliar na década de 90 e 2000 os fatores preditores de rejeição aguda (RA) aos 6 meses pós transplante renal (TR) e o seu efeito na sobrevida censurada do enxerto e do doente. Material e Métodos: Análise retrospetiva dos casos de RA efetuada separadamente em dois períodos: 1990-1999 e 2000-2009. Na avaliação dos fatores de risco para RA foi utilizado um modelo de regressão logística multivariada. Procedemos à construção de curvas comparativas de sobrevivência do enxerto entre paciente com e sem RA pelo método de Kaplan-Meier em cada período. A regressão de Cox multivariada permitiu identificar os preditores de sobrevivência censurada do enxerto e doente, usando como modelo: rejeição aguda, idade (< 40 vs ≥ 40 anos) e sexo do recetor, tempo em HD/DP (< 36 vs. ≥ 36meses), dador vivo vs. cadavérico (apenas na década de 2000), incompatibilidades HLA (0-3 vs. 4-6), PRA (≤ 15 vs. > 15%), número de TR prévios (< 2 vs. ≥ 2), status de hepatite B/C, idade (< 38 vs. ≥ 38 anos) e sexo do dador, episódio de necrose tubular aguda (NTA), uso de ATG na imunossupressão (IS) de indução, uso de MMF ou Tacrolimus (apenas na década de 2000) na IS de indução/manutenção. Resultados: Num total de 1299 transplantes renais, 644 (49.5%) foram realizados na década de 90 e 655 (50.5%) na década de 2000. A RA foi mais frequente na década de 90 (26.2% vs. 11.1%, p < 0.001). Nesta década, os fatores de risco para RA foram o não-uso de ATG (OR 1.88, p = 0.025) e a idade do recetor < 40 anos (OR 2.39, p = 0.001). Na década de 2000, NTA (OR 1.895, p = 0.046) e PRA > 15% (OR 3.519, p = 0.001) foram os fatores de risco identificados. A sobrevivência censurada do enxerto aos 5 anos foi inferior nos casos de RA na década de 90 (81% vs. 94%, p < 0.001) e 2000 (81% vs. 91%, log rank p = 0.004). Na análise de regressão Cox, os preditores de menor sobrevivência do enxerto na década de 90 foram a RA (HR 2,436, p < 0.001), idade do recetor < 40 anos (HR 1.984, p = 0.002) e idade do dador ≥ 38 anos (HR 1.961, p = 0.002). Na década de 2000 foram identificadas a NTA (HR 3.247, p < 0.001) e idade de dador ≥ 38 anos (HR 2.32, p = 0.017). Não encontramos diferenças na sobrevida do doente aos 5 anos em ambos períodos. Apenas o status de Hepatite B/C (HR 1.714, p = 0.023) foi preditor independente de morte do doente na década de 90, enquanto que na década de 2000, os preditores significativos foram TR prévio (HR 2,718, p = 0.049) e RA (HR 2,619, p = 0.023). Conclusão: A partir de 2000, a RA aos 6 meses deixou de ser um preditor independente de sobrevivência do enxerto. Inversamente, passou a ter um efeito negativo independente na sobrevivência do doente. Os avanços na IS permitiu o TR em recetores cada vez mais sensibilizados, com melhoria na sobrevida do enxerto nestes casos mas com possível efeito desfavorável na sobrevida do doente.

Objective: To determine risk factors for acute rejection in the first 6 months post- transplant and their effect on death-censored graft and patient survival in the 990-1999 and 2000-2009 periods. Patients and Methods: Retrospective analysis of acute rejection episodes was performed separately in two periods: 1990-1999 and 2000-2009. Multivariate logistic regression analysis was performed in order to identify risk factors for acute rejection. Death-censored graft and patient survival comparison between patients with or without acute rejection occurrence was performed by Kaplan-Meier analysis. Multivariate Cox regression analysis identified independent predictors for death-censored graft and patient survival, assuming the following model: acute rejection, patient’s age (< 40 vs. ≥ 40 years) and gender, time on haemodialysis / peritoneal dialysis (< 36 vs. ≥ 36 months), live vs. deceased donor (only after the year 2000), HLA mismatches (0-3 vs. 4-6), PRA (≤ 15 vs. > 15%), number of previous kidney transplants (< 2 vs. ≥ 2), status of hepatitis B/C, donor´s age (< 38 vs. ≥ 38 years) and gender, delayed graft function (DGF), ATG use in induction immunosuppression (IS), MMF or Tacrolimus use in induction / maintenance IS (after 2000). Results: A total of 1299 kidney transplants were analyzed. Acute rejection was more frequently diagnosed in the 1990s (26.2% vs. 11.1%, p < 0.001). Over this period, ATG non-use (OR 1.88, p = 0.025) and patients’ age < 40 years (OR 2.39, p = 0.001) were risk factors for AR while, after 2000, DGF (OR 1.895, p = 0.046) and PRA > 15% (OR 3.519, p = 0.001) were identified. Five years death-censored graft survival was lower in AR cases in the 1990s (81% vs. 94%, p < 0.001) and after 2000 (81% vs. 91%, log rank p = 0.004). Independent predictors for worse death-censored graft survival in 1990-1999 patients were AR (HR 2,436, p < 0.001), patient´s age < 40 years (HR 1.984, p = 0.002) and donor´s age ≥ 38 years (HR 1.961, p = 0.002), while after 2000, DGF (HR 3.247, p < 0.001) and donor´s age ≥ 38 years (HR 2.32, p = 0.017) were identified. No difference was found at five-year patient survival in both groups. Only hepatitis B/C (HR 1.714, p = 0.023) was identified as an independent predictor for patient death in the 1990-1999 period, while after 2000, retransplantation (HR 2,718, p = 0.049) and AR (HR 2,619, p = 0.023) were determinant. Conclusion: After the year 2000, AR was no longer an independent predictor for poor graft survival. Inversely, AR began to play a deleterious effect on patient survival. Advances on immunosuppressive drugs allowed the increase of kidney transplant on hypersensitized patients, with improvement of graft survival in those patients but also with a possible deleterious effect on patient survival.