ABSTRACT Objetives: The incidence of posttransplant diabetes and the elevated cardiovascular (CV) risk among transplant recipients are on the rise. Glucagon-like peptide agonists have the potential to mitigate the effects of immunosuppressive drugs, addressing both hyperglycemia and weight gain. This makes them appealing for use in this population, given their CV and renoprotective benefits. Nevertheless, there is insufficient substantial evidence regarding their efficacy in diabetic kidney transplant recipients (KTR). Methods: The objective of this retrospective study was to assess the effectiveness and safety of glucagon-like peptide agonists in KTR. The primary focus was to evaluate their impact on various parameters, such as hemoglobin A1c levels, body mass index (BMI), lipid panel, hemoglobin levels, renal allograft function (estimated glomerular filtration rate [eGFR]), and urinary protein-to-creatinine ratio. Results: During a median observation period of 18 months, this investigation included 64 renal transplant patients. Median eGFR at baseline was 61.9 mL/min/1.73 m2 and remained stable throughout the follow-up. Median HbA1cdecreased from 7.5 to 7% (95%CI; p < 0.002). A significant improvement in BMI and lipid panel were also observed. We did not observed significant changes regarding median creatinine and urinary protein:creatinine ratio levels. No side effects justified discontinuation of the drug. Conclusion: This study shows that the use of glucagon-like peptide agonists is feasible and well-tolerated in KTR, with no significant side effects observed. Subsequent studies are needed to explore whether glucagon-like peptide agonists can effectively improve allograft survival in these patients. Objetives (CV rise Glucagonlike Glucagon like drugs gain population benefits Nevertheless KTR . (KTR) Methods glucagonlike glucagon parameters Ac c levels BMI, , (BMI) estimated eGFR, [eGFR]) proteintocreatinine protein Results 1 months 6 patients 619 61 9 61. mLmin173 mLmin mL min 73 mL/min/1.7 m followup. followup follow up. up follow-up HbAcdecreased HbA cdecreased 75 7 5 7. 95%CI 95CI CI 95 (95%CI 0.002. 0002 0.002 0 002 0.002) proteincreatinine drug Conclusion welltolerated well tolerated (KTR (BMI [eGFR] mLmin17 mL/min/1. 000 0.00 00 [eGFR mLmin1 mL/min/1 0.0 mL/min/ 0. mL/min

RESUMO Objetivos: A incidência de diabetes pós-transplante e o aumento do risco cardiovascular entre os receptores de transplante estão em ascensão. Os agonistas do receptor de peptídeo semelhante ao glucagon têm o potencial de mitigar os efeitos dos medicamentos imunossupressores, abordando tanto a hiperglicemia quanto o aumento de peso, o que os torna atrativos para uso nesta população, dadas as suas vantagens cardiovasculares e renoprotetoras. No entanto, a evidência atual é insuficiente sobre a sua eficácia em receptores de transplante renal diabéticos (RTRD). Métodos: O objetivo deste estudo retrospectivo foi avaliar a eficácia e segurança dos agonistas do peptídeo semelhante ao glucagon-1 em RTRD. O foco principal foi avaliar o seu impacto em vários parâmetros, tais como níveis de hemoglobina A1c, índice de massa corporal (IMC), perfil lipídico, níveis de hemoglobina, função do enxerto renal (taxa de filtração glomerular estimada [TFGe]) e relação proteína-creatinina urinária. Resultados: Durante um período de observação mediano de 18 meses, esta investigação incluiu 64 pacientes transplantados renais. A TFGe mediana no início foi de 61,9 mL/min/1,73 m2 e permaneceu estável durante o acompanhamento. A mediana da HbA1c diminuiu de 7,5 para 7% (IC95%; p < 0,002). Também foi observada uma melhoria significativa no IMC e no perfil lipídico. Não foram observadas mudanças significativas nos níveis medianos de creatinina e relação proteína:creatinina urinária. Nenhum efeito colateral justificou a descontinuação do medicamento. Conclusão: Este estudo mostra que o uso de agonistas do peptídeo semelhante ao glucagon é viável e bem tolerado em RTRD, sem efeitos colaterais significativos observados. Estudos subsequentes são necessários para explorar se esta terapêutica pode melhorar efetivamente a sobrevida do aloenxerto nesses pacientes. Objetivos póstransplante pós ascensão imunossupressores peso população renoprotetoras entanto RTRD . (RTRD) Métodos glucagon1 1 glucagon- parâmetros A1c Ac c IMC, , (IMC) lipídico taxa [TFGe] proteínacreatinina proteína urinária Resultados meses 6 renais 619 61 9 61, mLmin173 mLmin mL min 73 mL/min/1,7 m acompanhamento HbAc HbA 75 7 5 7, IC95% IC95 IC (IC95% 0,002. 0002 0,002 0 002 0,002) medicamento Conclusão observados (RTRD (IMC [TFGe mLmin17 mL/min/1, IC9 (IC95 000 0,00 00 mLmin1 mL/min/1 (IC9 0,0 mL/min/ (IC 0, mL/min

ABSTRACT Introduction: Considering the rising occurrence of posttranplant diabetes and the elevated cardiovascular burden among transplant recipients, the utilization of SGLT2 inhibitors (SGLT2i) in this group is appealing because of their cardiovascular and renoprotective benefits. Nevertheless, there is a scarcity of evidence for diabetic kidney transplant recipients (DKTRs) owing to concerns about potential renal graft damage and adverse effects. Methods: This retrospective study was devised to assess the effectiveness and safety of SGLT2i in kidney transplant recipients (KTRs). The main focus was on evaluating their impact on parameters such as haemoglobin A1c levels, body mass index (BMI), lipid panel, haemoglobin levels, renal allograft function (estimated glomerular filtration rate) and urirnary protein-to-creatinine ratio. Results: A total of 75 renal transplant patients were included in this investigation. The study spanned a median observation period of 18 (2.0–71.0) months. Median estimated glomerular filtration rate at baseline was 61,9 (26–120) mL/min/1.73 m2 and remained stable throughout the follow-up. Median HbA1cdecreased from 7.5 to 7.0% (95% CI; p<0,002). A significant improvement in BMI (95% CI; p<0,001) and lipid panel (95% CI; p<0,05) were also observed. Median haemoglobin rate at baseline was 13,5g/dL and modestly improved at end of follow-up to 13,7g/dL (p=0,12). Regarding urinary protein:creatinine ratio, levels slightly but not significantly rose [+0.05 g/g (p=0,9)]. In a post-hoc subgroup analysis, the rate of urinary tract infections was low (10%). No other side effects were observed during the treatment course. Conclusions: This study demonstrates that the administration of SGLT2i is viable and well-tolerated, with no notable side effects observed in KTRs. However, the question of whether SGLT2i can effectively lower cardiovascular mortality and enhance allograft survival in these patients remains to be explored in subsequent studies. Introduction SGLT SGLTi i (SGLT2i benefits Nevertheless DKTRs (DKTRs Methods KTRs . (KTRs) Ac c BMI, , (BMI) proteintocreatinine protein creatinine ratio Results 7 investigation 1 2.0–71.0 20710 2 0 71 (2.0–71.0 months 619 61 9 61, 26–120 26120 26 120 (26–120 mLmin173 mLmin mL min 73 mL/min/1.7 m followup. followup follow up. up HbAcdecreased HbA cdecreased 5 7. 70 7.0 95% 95 (95 CI p<0,002. p0002 p p<0,002 002 p<0,002) p<0,001 p0001 001 p<0,05 p005 05 135gdL gdL 13 5g dL g 137gdL 7g p=0,12. p012 p=0,12 12 (p=0,12) proteincreatinine +0.05 005 [+0.0 gg p=0,9. p09 p=0,9 (p=0,9)] posthoc post hoc analysis 10%. 10 10% (10%) course Conclusions welltolerated, welltolerated well tolerated, tolerated well-tolerated However studies (KTRs (BMI 2.0–71. 2071 (2.0–71. 6 26–12 2612 (26–12 mLmin17 mL/min/1. (9 p000 p<0,00 00 p<0,0 p00 p01 p=0,1 (p=0,12 +0.0 [+0. p0 p=0, (p=0,9) (10% 2.0–71 207 (2.0–71 26–1 261 (26–1 mLmin1 mL/min/1 ( p<0, (p=0,1 +0. [+0 p=0 (p=0,9 (10 2.0–7 20 (2.0–7 26– (26– mL/min/ p<0 (p=0, +0 [+ p= (1 2.0– (2.0– (26 mL/min p< (p=0 + [ 2.0 (2.0 (2 (p= 2. (2. (p

RESUMO Introdução: Considerando o aumento da incidência de diabetes pós-transplante e o elevado impacto cardiovascular entre os receptores de transplantes, este facto faz com que o uso de inibidores de SGLT2 nesse grupo seja atrativo devido aos seus benefícios cardiovasculares e renoprotetores. No entanto, há escassez de evidência nos receptores de transplante renal com diabetes devido a preocupações com possíveis danos ao enxerto renal e efeitos adversos. Métodos: Este estudo retrospectivo foi elaborado para avaliar a eficácia e segurança dos inibidores de SGLT2 em receptores de transplante renal (KTRs). O foco principal foi avaliar o seu impacto em parâmetros como níveis de hemoglobina A1c, índice de massa corporal (IMC), perfil lipídico, níveis de hemoglobina, função do enxerto renal (taxa de filtração glomerular estimada) e relação proteína/creatinina urinária. Resultados: Um total de 75 pacientes receptores de transplante renal foram incluídos em nossa investigação. O estudo abrangeu um período de observação mediano de 18 (2,0–71,0) meses. A taxa média de filtração glomerular estimada no início foi de 61,9 (26–120) mL/min/1,73 m2 e permaneceu estável durante o acompanhamento. A mediana da HbA1c diminuiu de 7,5 para 7,0% (IC 95%; p<0,002). A melhora significativa no IMC (IC 95%; p<0,001) e no perfil lipídico (IC 95%; p<0,05) também foram observados. A taxa média de hemoglobina no início foi de 13,5g/dL e melhorou modestamente no final do acompanhamento para 13,7g/dL (p=0,12). Em relação à relação proteína/creatinina urinária, os níveis aumentaram ligeiramente, mas não significativamente [+0,05 g/g (p=0,9)]. Numa análise de subgrupo post-hoc, a taxa de infecções do trato urinário foi baixa (10%). Nenhum outro efeito colateral foi observado durante o curso do tratamento. Conclusões: Este estudo demonstra que a administração de inibidores de SGLT2 é viável e bem tolerada, sem efeitos colaterais notáveis em receptores de transplante renal. No entanto, a questão de saber se a inibição do SGLT2 pode efetivamente reduzir a mortalidade cardiovascular e melhorar a sobrevida do enxerto nesses pacientes permanece a ser explorada em estudos subsequentes. Introdução póstransplante pós transplantes SGLT renoprotetores entanto adversos Métodos KTRs. KTRs . (KTRs) A1c Ac c IMC, , (IMC) proteínacreatinina proteína creatinina urinária Resultados 7 investigação 1 2,0–71,0 20710 2 0 71 (2,0–71,0 meses 619 61 9 61, 26–120 26120 26 120 (26–120 mLmin173 mLmin mL min 73 mL/min/1,7 m HbAc HbA 5 7, 70 7,0 IC 95% 95 p<0,002. p0002 p p<0,002 002 p<0,002) p<0,001 p0001 001 p<0,05 p005 05 observados 135gdL gdL 13 5g dL g 137gdL 7g p=0,12. p012 p=0,12 12 (p=0,12) ligeiramente +0,05 005 [+0,0 gg p=0,9. p09 p=0,9 (p=0,9)] posthoc, posthoc post hoc, hoc post-hoc 10%. 10 10% (10%) tratamento Conclusões tolerada subsequentes (KTRs (IMC 2,0–71, 2071 (2,0–71, 6 26–12 2612 (26–12 mLmin17 mL/min/1, p000 p<0,00 00 p<0,0 p00 p01 p=0,1 (p=0,12 +0,0 [+0, p0 p=0, (p=0,9) (10% 2,0–71 207 (2,0–71 26–1 261 (26–1 mLmin1 mL/min/1 p<0, (p=0,1 +0, [+0 p=0 (p=0,9 (10 2,0–7 20 (2,0–7 26– (26– mL/min/ p<0 (p=0, +0 [+ p= (1 2,0– (2,0– (26 mL/min p< (p=0 + [ ( 2,0 (2,0 (2 (p= 2, (2, (p

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. Introduction (KT infections COVID19. COVID19 COVID 19. 19 Methods COVID-1 1 2020 15 2021 characteristics course treatment Results 12 72 male 545130 54 5 13 0 54.5±13. years asymptomatic 7 36 hospitalization 30 IMV, , (IMV) injury 10 dialysis 20 died SMR 3768 3 768 3.76 95% 95 (95 CI1.7237.154. CI17237154 CI 1.723 7.154 . 723 154 CI:1.723-7.154) OR 1275 275 1.275 P=0.001, P0001 P P=0.001 001 P=0.001) 0968 968 0.968 P=0.015, P0015 P=0.015 015 P=0.015) 13836 836 13.836 P=0.019 P0019 019 demand 3801 801 3.801 P=0.031 P0031 031 0955 955 0.955 P=0.005, P0005 P=0.005 005 P=0.005) andor or death Conclusion COVID1 COVID- 202 54513 54.5±13 (IMV 2 376 76 3.7 9 (9 CI1 7237 CI1.7237.154 CI1723715 1723 1.72 7154 7.15 CI:1.723-7.154 127 27 1.27 P000 P=0.00 00 096 96 0.96 P001 P=0.01 01 1383 83 13.83 380 80 3.80 P=0.03 P003 03 095 0.95 5451 54.5±1 37 3. ( CI1.7237.15 CI172371 172 1.7 715 7.1 CI:1.723-7.15 1.2 P00 P=0.0 09 0.9 138 8 13.8 38 3.8 545 54.5± CI1.7237.1 CI17237 17 1. 71 7. CI:1.723-7.1 P0 P=0. 0. 13. 54.5 CI1.7237. CI1723 CI:1.723-7. P=0 54. CI1.7237 CI172 CI:1.723-7 P= CI1.723 CI17 CI:1.723- CI1.72 CI:1.723 CI1.7 CI:1.72 CI1. CI:1.7 CI:1. CI:1 CI:

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. Introdução (TR infecções COVID19. COVID19 COVID 19. 19 Métodos COVID-1 º 202 1 2021 características clínico Resultados 12 72 masculino 545130 54 5 13 0 54,5±13, anos assintomáticos 7 36 internação oxigênio 30 VMI, , (VMI) aguda 10 diálise 20 óbito portuguesa TMP 3768 3 768 3,76 IC 95% 95 1,7237,154. 17237154 1,723 7,154 . 723 154 1,723-7,154) OR 1,275 1275 275 P=0,001, P0001 P P=0,001 001 P=0,001) 0,968 0968 968 P=0,015, P0015 P=0,015 015 P=0,015) 13,836 13836 836 P=0,019 P0019 019 3,801 3801 801 P=0,031 P0031 031 0,955 0955 955 P=0,005, P0005 P=0,005 005 P=0,005) eou ou Conclusão COVID1 COVID- 54513 54,5±13 (VMI 2 376 76 3,7 9 7237 1,7237,154 1723715 1723 1,72 7154 7,15 1,723-7,154 1,27 127 27 P000 P=0,00 00 0,96 096 96 P001 P=0,01 01 13,83 1383 83 3,80 380 80 P=0,03 P003 03 0,95 095 5451 54,5±1 37 3, 1,7237,15 172371 172 1,7 715 7,1 1,723-7,15 1,2 P00 P=0,0 0,9 09 13,8 138 8 3,8 38 545 54,5± 1,7237,1 17237 17 1, 71 7, 1,723-7,1 P0 P=0, 0, 13, 54,5 1,7237, 1,723-7, P=0 54, 1,7237 1,723-7 P= 1,723-

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.

ABSTRACT End stage kidney disease (ESKD) is a prevalent health issue across the world and it is well established that kidney transplantation (KT), specifically from a living donor, is currently the best value-based treatment method. Ergo, it is crucial to invest heavily in making this care strategy the best possible option for the majority of eligible patients. Barriers to the kidney transplant process are mainly related to education and accessibility: awareness of the clinical and societal relevance of the therapy must be promoted at the level of patients, clinicians and health providers. A health-literacy-focused website has been developed as part of this, aiming to provide the general population, particularly potential organ receptors and donors, with better access to trustworthy information and data. This was meant to be the effective expression of knowledge diffusion and innovation as a result of an academic master thesis. This communication-focused digital resource is designed to combat these obstacles and to create a long-lasting, positive and significant impact.

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.

RESUMO Objetivo: A tirosinemia tipo III (TT III) é a forma mais rara das tirosinemias e o espectro clínico desta entidade não está totalmente esclarecido. O envolvimento neurológico é variável, incluindo o atraso cognitivo ou transtorno do déficit de atenção com hiperatividade (TDAH). Descrevemos o caso de dois irmãos que foram diagnosticados com TT III em idades diferentes. Descrição dos casos: O caso índice foi diagnosticado no contexto do rastreio endócrino-metabólico neonatal, tendo iniciado imediatamente dieta hipoproteica, com redução consistente dos níveis de tirosina. Por volta dos três anos, foi detectado um comportamento hiperativo, tendo iniciado dois anos depois tratamento para o TDAH. Aos sete anos, apresenta leve melhora de comportamento e da atenção e avaliação cognitiva levemente inferior ou pouco abaixo quando comparado a crianças da mesma faixa etária, apesar de manter níveis aceitáveis de tirosina. A sua irmã, com história de TDAH desde os cinco anos, foi diagnosticada de TT III aos oito anos no contexto do rastreio de familiares. Apesar de iniciar tratamento dietético, nenhum efeito foi notado em termos de comportamento e a doente apresenta leve atraso cognitivo. Comentários: Este é o primeiro caso clínico descrito de irmãos com TT III que iniciaram terapêutica dietética com dieta hipoproteica em diferentes fases da vida, com melhor avaliação em termos neurológicos e comportamentais no doente que iniciou tratamento mais precocemente.

ABSTRACT Objective: Tyrosinemia type III (HT III) is the rarest form of tyrosinemia, and the full clinical spectrum of this disorder is still unknown. The neurological involvement varies, including intellectual impairment and attention deficit disorder with hyperactivity (ADHD). We report the case of two siblings diagnosed with HT III at different ages. Case description: The index case was diagnosed by newborn screening for endocrine and metabolic disorders, starting a low-protein diet immediately, with a consistent decrease in tyrosine levels. By the age of three, the child displayed a hyperactive behavior, starting treatment for ADHD two years later. At seven years of age, he shows a slight improvement in terms of behavior and attention span and has a cognitive performance slightly lower than his peers, despite maintaining acceptable tyrosine levels. His sister, who had a history of ADHD since age five, was diagnosed with HT III after family screening at the age of eight. Despite initiating a dietetic treatment, her behavior did not improve, and she has a mild intellectual impairment. Comments: This is the first case report describing siblings with HT III who underwent nutritional treatment with a low-protein diet in different phases of life, with a better neurological and behavioral evaluation in the patient who started treatment earlier.

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.

Abstract In Portugal, tetrahydrobiopterin (BH4)-responsive patients with phenylketonuria (PKU) are identified using a loading test (LT). Phenylalanine/natural protein (Phe/NP) intake is increased to elevate blood Phe prior to the LT. In a longitudinal retrospective study, the impact of Phe/NP titration post-LT in 58 patients (19.6 + 8.2 years) with PKU during 4 study periods (SPs) was examined. In SP1 (2010-2013), patients were diet treated only; in SP2 (2014), the Phe/NP titration was followed by the LT in SP3 (2015). In SP4 (2016), patients received diet treatment only (n ¼ 49) or BH4 þdiet (n ¼ 9). The median percentage blood Phe within the target range was higher in SP1 versus SP4 (64 [28-85] vs 45 [0-66]; P < .001). Our results suggest that transient Phe/NP titration, associated with a deliberate increase in NP, may adversely affect metabolic control. Controlled studies are necessary to examine the longer term impact of temporary increased NP with BH4 LT in non-BH4-responsive patients.

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