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As a complement to previous results obtained using the standard Microtox acute-toxicity test, which is based on measuring the rapid decrease of bioluminescence (5 to 30 minutes of exposure) in Vibrio fischeri bacteria in the presence of toxicants, the long-term effects of Cd(II), Cr(VI), and As(V) were studied on growth rate and viability assays of the same bacteria adapted to longer-lasting cultures, i.e., 48 or 72 hours instead of 5 or 30 minutes. Effects on viability or growth, as studied by establishing dose- and time-response curves, confirmed that these poisonous chemicals were not particularly toxic to these bacteria. Nevertheless, in the case of Cr(VI), the viability-inhibition assay appeared to be more sensitive than the Microtox acute-toxicity test. Interestingly, it was possible to observe a clear hormesis phenomenon, especially for Cd(II), under the conditions of both viability- and growth-inhibition assays.

Arsenic is an abundant metalloid and a dangerous pollutant when in solution under the arsenate or arsenite forms-As(V) and As(III), respectively. Since its biological effects are expected to depend on the oxidation state and on speciation, effect of pH on either As(V) or As(III) speciation and resulting toxicity was investigated using the Microtox bioassay based on change in light emission by the luminescent bacteria Vibrio fischeri. Within a 5.0-8.0 pH range, EC50 values for As(V) were found to decrease as pH became basic, reflecting an increase in toxicity; whereas in the case of As(III), EC50 values were almost unchanged within a 6.0-8.0 pH range and lowered only at pH 9.0. HAsO42- and H2AsO3-were found to be the most toxic species. A statistical approach based on testing the null hypothesis of additive toxicity revealed an antagonistic effect between the arsenate chemical species. At low concentrations, As(V) was regularly found to be more toxic than As(III), independent of the pH value. Conversely, at high concentrations, the toxicity of both As(III) and As(V) was found to chiefly depend on pH, as a consequence of the strong influence of this parameter on the chemical speciation.

The effect of organic arsenic compounds and inorganic As(V) and As(III) on Vibrio fischeri luminescence and butyrylcholinesterase activity were evaluated using Microtox and microcalorimetric analysis. Organic arsenic compounds were arsenocholine (AsC), arsenobetaine (AsB), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA) and the antibiotic 4-hydroxy-3-nitrobenzene arsonic acid (HNAA, Roxarsone^sup (R)^). HNAA, As(III) and As(V) were found to inhibit Vibrio fischeri light emission whereas MMA, DMA, AsC and AsB produced only a slight effect. By contrast, only AsC, AsB and As(III) were found to inhibit butyrylcholinesterase activity.[PUBLICATION ABSTRACT]

Lupus nephritis (LN) is the most frequent serious manifestation of patients with systemic lupus erythematosus (SLE). Up to 60% of SLE patients develop LN, which has a significant impact on their quality of life and prognosis. Recent advances have improved the diagnostic approach to LN, and new drugs that block specific pathways and kidney damage progression have been developed. Several randomized and well-powered clinical trials have confirmed the efficacy of these agents in terms of proteinuria remission and preservation of kidney function in the medium and long term, with an acceptable safety profile and good tolerance. The combination of different therapies allows for reduction of the dose and duration of corticosteroids and other potentially toxic therapies and leads to an increase in the number of patients achieving complete remission of the disease. This consensus document carried out by the Spanish Group for the Study of Glomerular Diseases (GLOSEN) provides practical and updated recommendations, based on the best available evidence and clinical expertise of participating nephrologists. Lay Summary This abridged version of the 2023 GLOSEN Consensus Document on Lupus Nephritis provides practical and up-to-date recommendations on the diagnosis, monitoring and treatment of patients with lupus nephritis (LN), including special situations such as frequently relapsing patients, refractory LN, pregnancy and thrombotic microangiopathy. These recommendations are based on the best available evidence and on the clinical experience of authors. The text is accompanied by tables and algorithms aiming to provide an easy-to-read document useful for the diagnosis and management of LN patients.

BackgroundThis study evaluated the efficacy and safety of avacopan versus a prednisone taper in the subgroup of patients with antineutrophil cytoplasmic antibody-associated vasculitis (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)) receiving cyclophosphamide (CYC) followed by azathioprine (or mycophenolate mofetil) in the ADVOCATE trial.MethodsKey efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included glucocorticoid toxicity, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and safety.ResultsOf 330 patients receiving study medication, 116 (35.2%) received CYC (avacopan group, n=59; prednisone taper group, n=57). Remission at week 26 and sustained remission at week 52 were achieved by 37/59 (62.7%) and 33/59 (55.9%) patients in the avacopan group and 34/57 (59.6%) and 30/57 (52.6%) in the prednisone taper group, respectively. Over 52 weeks, relapses were observed in 13.0% in the avacopan group and 22.6% in the prednisone taper group. Improvement in eGFR, speed of albuminuria reduction and differences in glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 55.9% and 56.1% of patients in the avacopan and prednisone taper groups, respectively.ConclusionsThis subgroup analysis of patients who received CYC shows similar rates of remission in the avacopan and prednisone taper groups. Compared with the prednisone taper regimen, the avacopan regimen was associated with a numerically lower relapse rate, greater improvement in eGFR, faster reduction in UACR, lower glucocorticoid-related toxicity and similar overall safety. These results support the use of avacopan in combination with CYC to treat GPA or MPA.Trial registration numberNCT02994927.

Este artículo tiene como objetivo realizar reflexiones teórico-epistemológicas en base a nuestras experiencias articuladas de investigación activista con perspectiva feminista. En base a un proceso de reflexión dialógica conjunta, compartimos algunas pistas de las dimensiones ético-político-afectivas de los procesos de investigación. Para ello ponemos en diálogo nuestros procesos de investigación con las epistemologías feministas y el intercambio con otras pensadorasinvestigadoras feministas.Proponemos poner en valor las relaciones de afecto y amistad, que permiten que nuestras investigaciones sean más habitables. Apostamos por una reflexividad que se deja afectar y atravesar por las emociones como herramienta del conocimiento. Incorporamos el análisis semiótico-material de nuestros propios cuerpos, no para caer en la autorreferencia, sino para contemplar sus efectos en la producción de conocimiento. En síntesis, proponemos otras posibilidades de producción de conocimiento desde las experiencias corporales, los afectos y las diversas relaciones que vamos tejiendo y que sostienen nuestros procesos de investigación para construir colectivamente un conocimiento encarnado y situado, comprometido con la constitución de modos de vida vivibles.

Background: Mycophenolate (MF) is effective as a maintenance therapy after induction therapy in patients with lupus nephritis (LN). However, little is known about its role in patients with impaired renal function. The purpose of this study was to evaluate the efficacy and safety of MF as a maintenance therapy for LN and its association with renal function. Methods: Data were obtained for 56 Spanish patients who were receiving MF as a maintenance therapy for LN. Patients were classified into two groups according to renal function at the initiation of MF treatment: group 1 [estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m 2 ] and group 2 (eGFR <60 ml/min/1.73 m 2 ). The primary endpoints of the study were the rates of renal relapse and responses, and their relationship with baseline renal function. Secondary outcomes were the appearance of side effects during treatment. Results: At initiation of MF treatment, the only differences between the groups were for age, hemoglobin levels, anti-DNA antibody titer, proteinuria, and renal function. In group 1 (n = 38), the eGFR was 98 ± 34 ml/min/1.73 m 2 and in group 2 (n = 18) the eGFR was 43 ± 14 ml/min/1.73 m 2 . Only 3 cases had an eGFR <30 ml/min/1.73 m 2 . No significant differences were observed in the rate of relapse at 6 months (group 1: 20%; group 2: 23%) or at 12 months (group 1: 25%; group 2: 17%). Response rates were also similar in both groups. Side effects were unremarkable. Conclusions: MF is effective and safe as a maintenance therapy for LN both in patients with normal renal function and in those with renal impairment.

Background The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. However, the information available in patients with moderate-severe chronic kidney disease is scarce. Methods The ALIMAR-C2 study is a case-control study to assess the association between metformin and lactic acidosis in patients with type 2 diabetes mellitus and moderate-severe chronic kidney disease. The study will be performed with computerized registered electronic health records from eight Spanish hospitals linked to their corresponding primary care health areas from 2010 to 2016, comprising approximately 22.1 million person-years of follow-up. Logistic regression will be used to assess the crude and adjusted risk of lactic acidosis associated with metformin use overall and stratifying by use and dose categories, and chronic kidney disease stage. The overall case fatality rate of lactic acidosis, as well as the case fatality rate stratified by chronic kidney disease stage, will be calculated. Discussion The ALIMAR-C2 study will provide useful information about the risk of lactic acidosis in type 2 diabetes mellitus patients with renal impairment using metformin.

Background: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. Methods: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m 2 ) and group 2 (eGFR <60 ml/min/ 1.73 m 2 ). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. Results: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m 2 ) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m 2 ). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. Conclusions: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.