ABSTRACT Primary hyperoxaluria type 1 is a rare genetic disease caused by mutations in AGXT, leading to an excessive hepatic production of oxalate, resulting in urolithiasis, nephrocalcinosis and chronic kidney disease. The authors present the case of a young female with PH1 who is the first patient treated with lumasiran in Portugal, and currently has a follow-up of 18 months.

Abstract Introduction: Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. Methods: We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. Results: Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. Discussion: Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Resumo Introdução: O diabetes mellitus tipo 1 está associado ao risco aumentado de doença arterial coronariana, que é frequentemente assintomática. Este risco aumenta significativamente em pessoas com nefropatia. Em pacientes selecionados, o transplante de pâncreas- rim simultâneo é a terapia substitutiva, renal e pancreática, de escolha, pois aumenta a longevidade e estabiliza complicações diabéticas. Apesar de essenciais, protocolos de triagem universais ainda são controversos para doença arterial coronariana nesta população. Métodos: Analisamos retrospectivamente 99 receptores de pâncreas-rim simultâneo de nosso centro, de 2011 a 2018, e selecionamos 77 pacientes que realizaram angiografia coronária durante avaliação pré-transplante. Nosso objetivo foi identificar fatores de risco potenciais associados a lesões significativas na angiografia coronária. Resultados: Quase metade de nossa coorte de 77 candidatos submetidos à angiografia coronária apresentou doença arterial coronariana. Destes, quase 30% foram submetidos à revascularização, embora apenas um tenha relatado sintomas de isquemia miocárdica. Em uma análise univariada, a presença do hábito de fumar foi o único fator de risco para doença arterial coronariana. Também descobrimos que 20 ou mais anos de diabetes mellitus tipo 1 estavam significativamente associados à presença de coronariopatia. Discussão: A seleção de candidatos diabéticos com risco cardíaco aceitável antes do transplante de pâncreas-rim simultâneo é imperativa. Dado o impacto de um diagnóstico correto e baixo risco de procedimento, defendemos o uso rotineiro da angiografia coronária como método de triagem inicial para doença arterial coronariana nesta população. Deve-se ter um cuidado especial na avaliação de pacientes assintomáticos com diabetes mellitus tipo 1 de longa duração e fumantes.

We report a case of a 63-year-old patient with recurrent nephrolithiasis for over 40 years and a significant family history of nephrolithiasis. The patient underwent full investigation at our department. He presented hypercalcemia, hypophosphatemia and hypercalciuria, with parathyroid hormone level in the normal range. A calcium load test and a fluorocholine PET-CT excluded primary hyperparathyroidism. Abnormal secretion of parathyroid hormone-related protein and sarcoidosis were also excluded. Genetic analysis showed mutations encoding for 25(OH)-vitamin D3-24-hydroxylase (CYP24A1) and Na-dependent phosphate cotransporter 2c (SLC34A3). This case affords insights into the biological pathways that underlie the role of genetic inheritance and accrued risk of development of nephrolithiasis.

Transplant options for patients with type 1 diabetes and end-stage kidney disease include deceased donor kidney, live donor kidney, simultaneous pancreas-kidney, pancreas after kidney and islet cell transplantation. Allocation of deceased donor kidneys is prioritized for candidates of multiorgan transplants. Here, outcomes of treatment modalities are reviewed, as well as the ethical implications of multiorgan allocation of kidney-pancreas.

Three sediment cores were collected in the muddy patches of the northern Portuguese Shelf located offshore the Douro and Minho rivers. Bivalves and worms were found in the upper and sub-surface layers of two cores. Vertical distributions of dissolved manganese and iron, iron oxides and acid volatile sulphide (AVS) in the bioturbated cores differ dramatically from those in the core where macrofauna was not observed. Also, Fe, Zn, Cu, Pb and Cd simultaneously extracted with AVS (1 M HCl) showed pronounced increases in concentrations deeper in the sediments. Where bioturbation was not visible the profiles of extractable Cu, Pb and Cd are consistent with the precipitation of downward diffusing dissolved metals. However, this redistribution did not affect the metal-total vertical profiles. Reactive metals exhibited multiple peaks in the irrigated sub-surface layers where AVS and dissolved Fe showed successive maxima and minima with the depth. We interpreted these profiles as the net result of dissolved oxygen being pumped into the sediment and the formation of several oxic/anoxic interfaces. At these depths trace metals are mobilized in the oxidized layers, diffused a few millimetres towards the layers where sulphide is present, and precipitated. The consequence of this internal redistribution was the broad maxima of total metal concentrations in irrigated sediment depths.

Se muestrearon tres testigos de sedimento en manchas de lodo procedentes de la plataforma continental del norte de Portugal localizadas frente a los ríos Duero y Miño. En las capas superficial y subsuperficial de dos de los testigos se encontraron bibalvos y gusanos. Las distribuciones verticales de hierro y manganeso disueltos, óxidos de hierro y sulfuros volátiles ácidos (AVS) en los testigos bioperturbados son drásticamente diferentes de aquellos en los que no se observó macrofauna alguna. De igual forma, el Fe, Zn, Cu, Pb y Cd extraídos simultáneamente con los AVS (HCl 1M), mostraron incrementos marcados en la concentración en zonas más profundas del sedimento. Donde la bioperturbación no fue visible, los perfiles de Cu, Pb y Cd extraíbles concuerdan con la precipitación y los metales disueltos con difusión descendente. Sin embargo, esta redistribución no afectó los perfiles verticales de metales totales. Los metales reactivos mostraron picos múltiples en capas irrigadas sub-superficiales donde los AVS y el Fe disuelto presentaron máximos y mínimos sucesivos con la profundidad. Interpretamos estos perfiles como el resultado neto del bombeo de oxígeno disuelto hacia el sedimento y la formación de varias interfases óxicas-anóxicas. En estas profundidades, los metales traza son movilizados en las capas oxidadas, y difundidos unos pocos milímetros hacia las capas donde hay sulfuro y éste precipita. La consecuencia de esta redistribución interna determina el máximo de las concentraciones totales de metales en profundidades con sedimentos irrigados.