RESUMO Introdução: Receptores de transplante renal são um subgrupo de doentes com maior risco de apresentar formas críticas de infecção por Síndrome Respiratória Aguda Grave pelo Coronavirus-2 (SARS-CoV-2) e piores outcomes devido ao tratamento imunossupressor. Aqui, apresentamos dados de uma coorte de um único centro de receptores de transplante renal com infecção por SARS-CoV-2. Métodos: Num estudo prospectivo, características basais, características clínicas, adaptação da terapêutica antiviral e de imunossupressão foram comparados entre doentes seguidos em ambulatório e doentes hospitalizados durante um período de um ano. Resultados: Foram analisados setenta e sete receptores de transplante renal, incluindo doentes de ambulatório e hospitalizados, com idade média de 57,7 (IIQ 49,7-64,9) anos. Vinte e oito (36,4%) foram tratados em ambulatório enquanto 49 (63,6%) doentes necessitaram de internação hospitalar. Entre os doentes hospitalizados, 18,4% foram admitidos na UTI, 49% apresentaram LRA, e 20,4% morreram. Foram realizados ajustes de imunossupressão em 95,9% dos pacientes hospitalizados, com dose de antimetabólitos ajustada em 83,7%, inibidores de mTOR em 14,3%, inibidores de calcineurina em 12,2%, e terapia com corticosteroides em 81,6%. Conclusão: Entre os pacientes hospitalizados, a optimização da terapêutica imunossupressora incluiu redução ou retirada de antimetabólito e aumento da dose de corticosteroides. A LRA ocorreu em quase metade dos pacientes e a mortalidade em pacientes hospitalizados atingiu 20%, refletindo uma maior gravidade da doença em relação à população em geral.

ABSTRACT Introduction: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. Methods: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. Results: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. Conclusion: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

ABSTRACT Introduction: The severe acute respiratory syndrome coronavirus 2 pandemic caused a negative impact on transplantation worldwide. One of the complexities is the management of the immunosuppression and anti-viral medication in transplant recipients. Herein we describe our experience managing five patients with coronavirus disease 2019 (COVID-19) immediately after kidney transplant. Description: we describe a series of five transplant recipients. Two were submitted to a low immunological risk induction immunosuppression: one developed severe disease, the other developed critical disease. The remaining three were submitted to a high immunologic risk immunosuppression: one developed mild disease, but approximately two months after diagnosis developed moderate COVID-19; another developed severe COVID-19; the remaining patient developed critical illness and perished. Both patients with critical COVID-19 developed bacterial and fungal superinfections in the Intensive Care Unit. All eligible patients were submitted to remdesivir and dexamethasone. The anti-metabolite was reduced or suspended. Despite worsening kidney function during the acute phase, kidney replacement therapy was only needed in one patient and the average serum creatinine at the time of discharge was lower that the pre-COVID-19 nadir. Discussion: There is still no definitive answer on whether solid organ transplant recipients carry a higher risk for morbimortality. Risk factors for the general population can also affect their outcome. The prolonged viral shedding in recipients may explain the irregular evolution of the patient who developed COVID-19 months after the initial diagnosis. The reduction of immunosuppression can be problematic in early post-transplant, but no apparent signs of rejection were noted. Literature addressing this specific context is scarce and studies are needed to clarify the optimal management of these patients.

Severe hypertriglyceridemia is defined as a serum triglyceride level >885mg/dl. It is an uncommon condition associated with serious complications, mainly acute pancreatitis. Treatment includes lifestyle changes, medical therapy and, more recently, extracorporeal apheresis techniques. Herein, we report a case of severe hypertriglyceridemia managed with therapeutic plasma exchange. Our patient presented with severe upper abdominal pain. Bloodwork showed extremely severe hypertriglyceridemia (14871mg/dl) and hypercholesterolemia (1536mg/dl) with only slight elevation of amylase and lipase and no echographic signs of acute pancreatitis. Two sessions of therapeutic plasma exchange were performed, with a mean 3L of plasma treated per session. The triglyceride levels dropped to 2325mg/dl after the first session and to 1207mg/dl after the second. Medical therapy was started, and the patient was discharged a week later. After 36 months of follow-up she remains stable, with triglyceride levels 427mg/dl. In this case therapeutic plasma exchange was an effective and well tolerated treatment for severe hypertriglyceridemia

Introduction: Kidney transplant (KT) recipients are highly susceptible to urinary tract infections (UTIs). Few data are available regarding the effects of cranberry products in KT recipients. Subjects and methods: This was a randomized double-blind study comparing daily treatment with a cranberry capsule versus a placebo capsule for 6 months. The study protocol was conducted in accordance with the Helsinki Declaration and was approved by the local ethics committee. The study group comprised women undergoing KT for over 1 year, and the exclusion criteria included simultaneous antibiotic UTI prophylaxis. The primary endpoint was UTI occurrence, and the secondary endpoints were the time to first UTI, hospitalization, antibiotic resistance, graft function, immunosuppressive dose changes, and side effects. Results: 55 KT women at a single centre were included as follows: 25 were randomized to the cranberry group, and 30 were assigned to the placebo group. During the study period, 16.4% of the participants presented with a UTI. A diagnosis of UTI within the previous year and KT duration, but not cranberry use (p=0.95) were independent predictors of UTI. Discussion: Cranberry capsules appear to be safe in KT women; however, no clinical efficacy of UTI prophylaxis was demonstrated in this well-designed but underpowered study. Further multicentric and longer trial should be performed to determine cranberry clinical efficacy

Introducão: A doença renal crónica provoca a diminuição da fertilidade. Com a transplantação renal a ferti- lidade é recuperada em poucos meses. Objetivo: Analisar a viabilidade da gravidez no transplante renal e o seu impacto sobre a função renal, as complicações na mulher e no recém-nascido. Métodos: Estudo retro- spectivo das gravidezes ocorridas em transplantadas renais entre 1985 e 2014 numa Unidade de Transplantação, com um follow-up de 12 meses pós gravidez. Resultados: Foram incluídas 18 gravidezes (1 gravidez gemelar) em 13 transplantadas renais com uma média de idades de 31 anos. Destas, 12 gravidezes progrediram, 5 resultaram em aborto espontâneo e 1 em aborto induzido. Apenas uma gravidez se complicou por diabetes gestacional. Ocorreram dois nados-mortos (gravidez gemelar). O peso médio dos 11 recém-nascidos foi de 2,6 kg. Verificou-se uma diminuição significativa da taxa de filtração glomerular estimada aos 3 meses pós parto [p < 0.05], mas 1 ano pós parto a tendência deixou de ser significativa [p> 0.05]. Relativamente à proteinuria, o aumento significativo aos 3 meses pós parto manteve-se aos 12 meses [p < 0.05]. No 3o trimestre verificou-se um aumento significativo da tensão arterial [p < 0.05], que não se manteve aos 12 meses pós parto [p > 0.05]. Nos doentes sob ciclosporina verificou-se uma diminuição dos níveis séricos [p < 0.05] ao longo da gravidez. Não se detetou nenhuma rejeição assim como falência do enxerto durante a gravidez ou no follow-up pós parto. Conclusão: Embora a amostra seja limitada, o número de abortos espontâneos foi superior ao da população geral (24% versus 8 a 20%). O aumento significativo da proteinuria mantido após um ano sugere o aumento do risco de disfunção do enxerto a longo prazo. A diminuição dos níveis séricos de ciclosporina ao longo da gravidez implica uma vigilância mais apertada deste parâmetro neste período

Background: Chronic kidney disease causes decreased fertility. With kidney transplantation, fertility is restored within a few months. Objective: To analyse the feasibility of pregnancy with renal transplantation and its impact on renal function, complications in women and newborns. Methods: Retrospective study of pregnancies that occurred in kidney transplant recipients between 1985 and 2014 in one Transplantation Unit, with a follow-up of 12 months post-partum. Results: Eighteen pregnancies were included (one twin pregnancy) in 13 kidney transplant recipients with an average age of 31 years. Of these, 12 pregnancies progressed, five resulted in miscarriage and one in abortion. Only one pregnancy was complicated by gestational diabetes. There were two stillbirths (twin pregnancy). The average weight of 11 newborns was 2.6 kilograms. There was a significant decrease of estimated glomerular filtration rate at 3 months post-partum [p < 0.05], but a year after delivery, the tendency was not maintained [p > 0.05]. Regarding proteinuria, the significant rise at 3 months was maintained until one year [p <0.05]. A significant increase in blood pressure was observed only on the 3rd trimester [p < 0.05], which did not maintain a year after delivery [p > 0.05]. In patients taking cyclosporine, a decrease in serum levels [p < 0.05] was found throughout the pregnancy. No rejection was detected, as well as graft failure during pregnancy or post-partum follow-up. Conclusion: Although the sample is limited, the number of miscarriages was higher than in the general population (24% versus 8 to 20%). The significant increase of the proteinuria throughout a year suggests a long-term increased risk of graft dysfunction. The decrease in serum cyclosporine levels during pregnancy implies a tighter monitoring of this parameter throughout this period

Uma transplantada renal de 50 anos, pós menopáusica, com dor óssea, osteoporose, hipercalcémia persistente e níveis elevados de paratormona, apesar de uma razoável função do enxerto renal, foi tratada com bifosfonatos e cinacalcet com início 5 e 6 meses, respectivamente, após a transplantação renal. Verificouse melhoria da densidade óssea medida por DEXA. Foi realizada uma biópsia óssea que revelou um resultado inesperado e preocupante. A doença óssea após a transplantação renal é diferente da DMO-DRC clássica e deve ser gerida de forma distinta. Nalguns casos, como o ilustrado na presente apresentação, justifica-se o diagnóstico invasivo através do recurso à realização de uma biópsia óssea, como é proposto nas orientações da KDIGO.

A 50-year-old post-menopausal recipient of a kidney allograft with bone pain, osteoporosis, persistent hypercalcaemia and elevated parathormone (PTH) levels, despite a satisfactory graft function, was treated with bisphosphonates and cinacalcet starting, respectively, 5 and 6 months after renal transplantation (RT). Sixteen months after treatment, there was improvement of bone mineral density (BMD) measured by dualenergy X-ray absorptiometry (DEXA). A bone biopsy was taken, unveiling a surprising and worrisome result. Post-RT bone disease is different from classic CKD-MBD and should be managed distinctly, including, in some difficult cases, an invasive evaluation through the performance of a bone biopsy, as suggested in the KDIGO guidelines.

Introdução: Os mTOR mostraram-se eficazes na imunossupressão de manutenção em relação à sobrevida do enxerto, mas o seu impacto na sobrevida do doente só recentemente foi avaliado. Neste estudo analisámos todos os doentes transplantados renais na nossa unidade desde 2006/01/01 até 2011/12/31 no que respeita à falência do enxerto e à mortalidade comparando os doentes que foram convertidos para mTOR com os que permaneceram sob inibidor da calcineurina (CNI).População e métodos: Foram avaliados 425 doentes (idade média de 46 ± 13 anos, 60,7% do sexo masculino, 10,1%, diabéticos com tempo médio de seguimento de 44 meses). Durante este período, 123 doentes foram convertidos para mTOR: 8, incluídos no protocolo de um estudo, 13 por neoplasia e 102 por evidência de disfunção crônica do enxerto. Os restantes doentes foram mantidos sob CNI. A sobrevida do enxerto e do doentes foram comparados por Kaplan-Meier e p<0,05 foi considerado significativo.Resultados: Durante o tempo de seguimento, 10 doentes morreram e 28 perderam o enxerto. As características basais foram semelhantes para ambos os grupos, com excepção da idade (os doentes convertidos eram mais velhos, p = 0,012), sexo (masculino mais frequente no grupo mTOR grupo, p = 0,04) e raça (os caucasianos foram mais prevalentes no grupo mTOR, p = 0,012).Não houve diferença entre os dois grupos na sobrevida do enxerto ou do paciente, mesmo após ajuste para idade, sexo, presença de diabetes mellitus ou risco imunológico. Além disso, no subgrupo de doentes com baixo risco imunológico, o uso de mTOR foi associado a uma tendência para a melhoria da sobrevivência dos enxertos renais, embora não estatisticamente significativa (p = 0,06).Conclusão: Apesar do pior prognóstico conferido pelas principais indicações para a conversão de inibidores de mTOR (neoplasia ou disfunção crônica do enxerto) e da idade avançada, não foi encontrada diferença na sobrevida do enxerto ou do doente entre os dois grupos. Em doentes com baixo risco imunológico, o grupo mTOR mostrou uma tendência para melhor sobrevida do enxerto.

Background: Inhibitors of the mammalian target of rapamycin (mTOR) have demonstrated a similar outcome on allograft loss but its impact on patient survival has only recently been evaluated. In this outcome analysis all renal transplants performed at our unit since 1/1/2006 until 12/31/2011, were evaluated. Allograft failure and mortality were compared between patients who were converted to mTOR and those who remained on a calcineurin inhibitor (CNI). Population and Methods: We have evaluated 425 patients (mean age 46±13 years, 60.7% male, 10.1% diabetics, mean follow-up of 44 months). During this period, 123 patients were converted to mTOR: 8 included in a protocol study, 13 due to malignancy and 102 to evidence of chronic pallograft dysfunction. The remaining patients were maintained on a CNI -based regimen. We compared patient and graft survival by Kaplan-Meier analysis and p < 0.05 was considered significant. Results: During the follow-up time, 10 patients died and 28 lost their graft. Baseline characteristics were similar, except for age(converted patients were older, p = 0.012), gender (higher male percentage in mTOR group, p = 0.04) and race (Caucasians were more prevalent in mTOR arm, p = 0.012). There was no difference between the 2 groups on either graft or patient survival, even after adjustment for age, gender, and presence of diabetes mellitus or immunological risk. Moreover, in the subgroup of patients with low immunological risk, the use of mTOR was associated with a trend towards improved renal allograft survival, although not statistically significant (p = 0.06). Conclusion: Despite worse prognosis conferred by the major indications for conversion to mTOR inhibitors (malignancy or chronic allograft dysfunction) and older age, we found no difference on allograft or patient survival between the 2 groups (mTOR versus CNI -based regimen). In patients with low immunological risk, mTOR group showed a trend towards better allograft survival.

Background. Bortezomib, a 26S proteasome inhibitor, is a novel treatment for refractory acute rejection. The main mechanism proposed for its action is the induction of apoptosis of mature plasma cells leading to an interruption of donor-specific antibody production, but other properties may also be involved. Patients and Methods. Four patients presenting with antibody-mediated rejection were treated with bortezomib as rescue therapy. Renal function, proteinuria and anti-HLA antibodies were monitored for 1-3 years. Results. In three cases, graft function recovery and decreased proteinuria occurred, despite the maintenance of donor-specific antibody levels. However, in one case graft function was lost. Side effects were mostly transient. There were no episodes of opportunistic infection. Conclusion. Bortezomib may be effective in antibodymediated rejection by different mechanisms than simply through reducing donor-specific antibody levels. The timing of its introduction and the length of time that donor-specific antibodies have been present may be determinants of its efficacy

The improvement of combined antiretroviral therapy regimens has made solid organ transplantation a therapeutic option for patients with human immunodeficiency virus (HIV) infection. Generally, HIV-2 infectionpresents a slower clinical progression and immunological degradation than HIV-1. HIV-2 infection treatment can be challenging when a complex immunosuppressive regimen is combined with antiretroviraltherapy. The authors report the first case in Portugal of renal transplantation in an HIV-2 patient. A 54-year-old man from Guinea-Bissau was diagnosed with HIV-2 infection on starting haemodialysis in Portugal in 1998. At diagnosis, HIV infection staging revealed undetectable plasma HIV- 2 RNA and T-cell CD4 counts of 808 cells/μl, with no need for combined antiretroviral therapy during follow-up. The patient underwent renal transplantation from a deceased donor in March 2011. He developed delayed graft function and started therapy with methylprednisolone and thymoglobulin. The patient gradually recovered renal function and was discharged after two weeks with serum creatinine of 2.3 mg/dL. The HIV-2 RNA levels remained undetectable, but T-cell CD4count decreased to less than 200 cells/μl and combined antiretroviral therapy with abacavir, lamivudine and raltegravir was started. Nine months after transplantation, the patient has a serum creatinine of 1.5 mg/dL and a nonreplicating HIV status