An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International

Approval of the vasopressin V2 receptor antagonist tolvaptan—based on the landmark TEMPO 3:4 trial—marked a transformation in the management of autosomal dominant polycystic kidney disease (ADPKD). This development has advanced patient care in ADPKD from general measures to prevent progression of chronic kidney disease to targeting disease-specific mechanisms. However, considering the long-term nature of this treatment, as well as potential side effects, evidence-based approaches to initiate treatment only in patients with rapidly progressing disease are crucial. In 2016, the position statement issued by the European Renal Association (ERA) was the first society-based recommendation on the use of tolvaptan and has served as a widely used decision-making tool for nephrologists. Since then, considerable practical experience regarding the use of tolvaptan in ADPKD has accumulated. More importantly, additional data from REPRISE, a second randomized clinical trial (RCT) examining the use of tolvaptan in later-stage disease, have added important evidence to the field, as have post hoc studies of these RCTs. To incorporate this new knowledge, we provide an updated algorithm to guide patient selection for treatment with tolvaptan and add practical advice for its use

Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented

pMINERVA: A donor–acceptor system for the in vivo recombineering of scFv into IgG molecules

Phage display is the most widely used method for selecting binding molecules from recombinant antibody libraries. However, validation of the phage antibodies often requires early production of the cognate full-length immunoglobulin G (IgG). The conversion of phage library outputs to a full immunoglobulin via standard subcloning is time-consuming and limits the number of clones that can be evaluated. We have developed a novel system to convert scFvs from a phage display vector directly into IgGs without any in vitro subcloning steps. This new vector system, named pMINERVA, makes clever use of site-specific bacteriophage integrases that are expressed in E. coli and intron splicing that occurs within mammalian cells. Using this system, a phage display vector contains both bacterial and mammalian regulatory regions that support antibody expression in E. coli and mammalian cells. A single-chain variable fragment (scFv) antibody is expressed on the surface of bacteriophage M13 as a genetic fusion to the gpIII coat protein. The scFv is converted to an IgG that can be expressed in mammalian cells by transducing a second E. coli strain. In that strain, the phiC31 recombinase fuses the heavy chain constant domain from an acceptor plasmid to the heavy chain variable domain and introduces controlling elements upstream of the light chain variable domain. Splicing in mammalian cells removes a synthetic intron containing the M13 gpIII gene to produce the fusion of the light chain variable domain to the constant domain. We show that phage displaying a scFv and recombinant IgGs generated using this system are expressed at wild-type levels and retain normal function. Use of the pMINERVA completely eliminates the labor-intensive subcloning and DNA sequence confirmation steps currently needed to convert a scFv into a functional IgG Ab

Fitorremediação de solos contaminados com tebuthiuron utilizando-se espécies cultivadas para adubação verde Phytoremediation of tebuthiuron-contaminated soils using species cultivated for green manure

O emprego da fitorremediação na despoluição de solos contaminados com compostos orgânicos, inclusive herbicidas, vem sendo pesquisado ultimamente. Como o tebuthiuron pode causar sério impacto ambiental, por ser muito utilizado, apresentar longo efeito residual no solo e possibilidade de contaminação do lençol de água subterrâneo, desenvolveu-se este trabalho com o objetivo de avaliar a capacidade de sete espécies vegetais na despoluição de solos contaminados com esse herbicida. As espécies avaliadas neste experimento foram: Cajanus cajan, Canavalia ensiformes, Dolichos lablab, Pannisetum glaucum, Estizolobium deeringianum, Estizolobium aterrimum e Lupinus albus. Elas foram semeadas e cultivadas, por 60 dias, em vasos cujo solo recebeu quatro doses do tebuthiuron (0,0; 0,5; 1,0; e 1,5 kg ha-1). As testemunhas foram constituídas por vasos sem planta, aos quais foram aplicadas as mesmas doses de herbicidas. Aos 60 dias após a semeadura, colheu-se a parte aérea de todas as plantas, sendo semeada, nos mesmos vasos, Avena strigosa, utilizada como planta indicadora, para realização do bioensaio. Depois de 60 dias da semeadura da espécie bioindicadora, esta foi colhida, sendo avaliadas as seguintes características: altura de plantas, sintomas de toxicidade e biomassa seca da parte aérea das plantas. Até a dose de 0,5 kg ha-1 de tebuthiuron, a espécie que melhor fitorremediou esse herbicida no solo foi L. albus. Quando o solo foi tratado com 1,0 kg ha-1 de tebuthiuron, C. ensiformes foi a espécie que melhor fitorremediou o herbicida. Isso foi concluído com base na maior altura de plantas, biomassa seca da parte aérea e menor toxicidade de A. strigosa, quando foi cultivada em sucessão a essas plantas remediadoras. Nenhuma das espécies avaliadas cresceu em solo que recebeu a maior dose de tebuthiuron (1,5 kg ha-1).<br>Phytoremediation of soil contaminated by organic compounds, including herbicides, is being widely investigated. The frequent use of tebuthiuron can cause serious environmental impacts such as long-term residual effect on soil and likely underground water contamination. Thus, this work aimed to evaluate the phytoremediation potential of seven plant species in soils treated with this herbicide. The experiment evaluated the following species: Cajanus cajan, Canavalia ensiformes, Dolichos lablab, Pannisetum glaucum, Estizolobium deeringianum, Estizolobium aterrimum and Lupinus albus, sown and cultivated for 60 days in vases treated with tebuthiuron at 0.0, 0.5, 1.0, and 1.5 kg ha-1. The control treatments were constituted by vases without plants, submitted to the same herbicide doses. Sixty days after sowing, the aerial part of all the plants was harvested and Avena strigosa was sown in the same vases for bioassay. Sixty days after it was sown, A. strigosa was harvested and the characteristics plant height, phytotoxicity symptoms and dry biomass of the aerial part of the plant were evaluated. Up to a tebuthiuron dose of 0.5 kg ha-1, L. albus presented the best phytoremediation results. When tebuthiuron was applied at 1.0 kg ha-1, C. ensiformes presented the best phytoremediation results. Such results were based on plant height, dry biomass of the aerial part and lower A. strigosa phytotoxicity when cultivated after these remediating plants. None of the species evaluated grew in soil receiving the highest dose of tebuthiuron (1.5 kg ha-1)