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Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) constituent une avancée considérable dans la prise en charge des patients diabétiques, des patients insuffisants cardiaques et des patients ayant une maladie rénale chronique (MRC). Des études contrôlées randomisées ont montré une réduction significative du risque cardiovasculaire chez des patients diabétiques de type 2 ou insuffisants cardiaques à fraction d'éjection altérée. Ces études retrouvaient une diminution de la dégradation de la fonction rénale, inspirant des études contrôlées randomisées chez des patients MRC : CREDENCE, DAPA-CKD et EMPA-KIDNEY. Les iSGLT2 sont associés à une diminution de l'évolution de la MRC vers la suppléance, de la pente de DFG et de l'albuminurie. Chez les patients MRC protéinuriques avec ou sans diabète, les études DAPA-CKD et EMPA-KIDNEY ont démontré l'effet néphroprotecteur. Cet effet ne semble pas être retrouvé pour les patients non protéinuriques. Pour les autres néphropathies, des études complémentaires sont nécessaires pour confirmer les premiers résultats chez les patients protéinuriques non diabétiques de type 2. L'indication des iSGLT2, en association aux bloqueurs du SRAA à doses maximales tolérées, paraît donc indéniable dans une optique de néphroprotection optimale chez les patients MRC diabétiques de type 2 ou albuminuriques ou insuffisants cardiaques. Leur prescription doit se faire en adjonction des traitements et des mesures de néphroprotection et de cardioprotection conventionnels. La tolérance est bonne. Cependant, une éducation et une surveillance particulière concernant les risques infectieux génitaux et d'acidocétose euglycémique (patients diabétiques) doivent être mises en place. Ainsi, l'arsenal thérapeutique pour les patients MRC s'étoffe, permettant d'envisager une personnalisation des traitements en fonction de la néphropathie sous-jacente. © 2022 Publié par Elsevier Masson SAS au nom de Société francophone de néphrologie, dialyse et transplantation. Inhibitors of sodium glucose co-transporter type 2 (iSGLT2) constitute a considerable advance in the management of patients with diabetes, heart failure and with chronic kidney disease (CKD). Randomized controlled studies have shown a significant reduction of cardiovascular risk in diabetic type 2 and/or heart failure with reduced ejection fraction patients. These studies observed a risk reduction of worsening nephropathy, leading to randomized controlled studies in CKD patients : CREDENCE, DAPA-CKD and EMPA-KIDNEY. iSGLT2 are associated with a slower progression toward end-stage kidney disease, a lower slope of GFR and a lower rate of albuminuria. In CKD patients with proteinuria either diabetic or not, the DAPA-CKD and the EMPA-KIDNEY studies have demonstrated a nephroprotective effect. This effect has not been found for patients without proteinuria. For the other nephropathies, further studies are required to confirm results obtained in patients without type 2 diabetes and macroalbuminuria. Therefore, the indication of iSGLT2, with appropriate dose of RAS inhibitor, seems undeniable to an optimal nephroprotection in CKD patients with type 2 diabetes and/or albuminuria and/or heart failure. They must be prescribed in addition to conventional nephroprotective and cardioprotective treatments and care. Side effects are limited. However, special education and monitoring concerning risks of genital infection and euglycemic ketoacidosis (diabetic patients) must be taken in mind. The therapeutic arsenal for CKD patients is expanding, leading to consider a personalized care according to the underlying nephropathy. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation. [ABSTRACT FROM AUTHOR]

Objectives: Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in ANCA-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement., Methods: In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30 mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form., Results: Among the 31 patients (median age 72 years), 10 had a relapsing AAV, twenty had anti-myeloperoxidase antibodies, and thirty had kidney vasculitis. Induction regimen included rituximab (n = 27), cyclophosphamide (n = 2), or both (n = 2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favorable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35 mL/min/1.73m2 [23; 45] at month 12 (p< 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration)., Conclusions: The GCs' sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The optimal regional anticoagulation (RA) of dialysis filters in patients at risk of bleeding remains elusive. Inducing hypocalcemia within the filter by using a calcium-free dialysate has emerged as an easy-to-use heparin-free RA, including in critically ill patients, but comparative studies are lacking., Methods: We conducted a multicentre, randomized, crossover trial to compare the efficacy and tolerance of two RAs (heparin-coated membrane (HCM) or calcium free dialysate with calcium reinjection according to ionic dialysance (CFD)) in patients requiring hemodialysis and at risk of bleeding. During the study period, each patient received two dialysis sessions (one with each RA in a randomly assigned order). The primary endpoint was the proportion of dialysis sessions completed (≥ 240 min)., Results: 94 patients were included in the intention-to-treat analysis, including 16 critically ill patients (17.0%). Coagulation and inflammation parameters, as well as hemodynamic status at baseline, were balanced between groups. Premature coagulation of the filter occurred in 19 HCM (20.9%) compared to 3 (3.2%) CFD sessions. In half of the sessions with premature termination, coagulation occurred before 180 minutes. The proportion of patients who completed the CFD session while failing to complete the HCM session (n = 17) was significantly higher than the proportion of patients who completed the HCM session while failing to complete the CFD session (n = 1; p < 0.001). Hemodynamic and metabolic tolerance were not different between groups., Conclusions: In individuals at risk of bleeding, RA with calcium-free dialysate significantly reduces the incidence of premature dialysis termination compared to heparin-coated membrane without safety concerns. Trial registration and statistical analysis plan: ClinicalTrials.gov identifier: NCT03842657., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known., Methods: Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models., Results: After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially cytomegalovirus (CMV) syndromes and diseases (213/544, 39%). One-third of the infected patients experienced at least two opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than after that (34.7 infections for 100 patient-years vs 3.64). Opportunistic infections associated with the age of the donor (P = .032), the age of the recipient (P = .049), the CMV serostatus (P < 10-6), a higher class II HLA mismatch (P = .032) and an induction treatment including rabbit anti-thymocyte globulins (P = .026). Repeated opportunistic infections associated with each other (P < 10-6) and with renal death (P < 10-6)., Conclusion: Opportunistic infections occur with a two-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. To answer these issues, the formation of an intra-volume channel within a three-dimensional, scaffold free, mature, and cell-covered collagen microfibre is here investigated through laser-induced cavitation. An intra-volume channel was formed upon irradiation with a near-infrared, femtosecond laser beam, focused with a high numerical aperture lens. The laser beam directly crossed the surface of a dense and living-cell bilayer and was focused behind the bilayer to induce channel formation in the hydrogel core while preserving the cell bilayer. Channel formation was assessed through confocal microscopy. Channel generation inside the hydrogel core was enhanced by the formation of voluminous cavitation bubbles with a lifetime longer than 30 s, which also improved intra-volume channel durability. Twenty-four hours after laser processing, cellular viability dropped due to a lack of sufficient hydration for processing longer than 10 min. However, the processing automation could drastically reduce the cellular mortality, this way enabling the formation of hollowed microfibres with a high density of living-cell outer bilayer.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects different organs and caused by loss-of-function mutations in one of two genes: TSC1 or TSC2. TSC1 or TSC2 gene mutation lead to dysfunction of hamartin or tuberin, respectively. Hamartin and tuberin form a protein complex that helps regulate cellular proliferation. These proteins form a complex that constitutively inhibits the mammalian target of rapamycin (mTOR) signaling pathway, leading to permanent activation of mTOR signaling within all TSC-associated lesions. Major features of TSC include tumors of the brain, skin, heart, lungs and kidneys, seizures and TSC-associated neuropsychiatric disorders, which can include autism spectrum disorder and cognitive disability. These disorders are usually diagnosed in children and adults. Specific guidelines for diagnosis, surveillance, and management have been proposed by the International Tuberous Sclerosis Complex Consensus Group. Several randomized controlled trials led to regulatory approval of the use of mTOR inhibitors for the treatment of renal angiomyolipomas, brain subependymal giant cell astrocytomas, refractory epilepsy and pulmonary lymphangioleiomyomatosis., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: Rabbit antithymocyte globulin (rATG) induction is associated with profound immunosuppression, leading to a higher risk of cytomegalovirus (CMV) infection compared with anti-interleukin 2 receptor antibody (anti-IL-2RA). However, this risk, depending on the baseline CMV serological recipient/donor status, is still controversial., Methods: The CMV DNAemia-free survival between rATG- and anti-IL-2RA-treated patients was analyzed in donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients in 1 discovery cohort of 559 kidney transplant recipients (KTRs) and 2 independent cohorts (351 and 135 kidney KTRs). The CMV-specific cell-mediated immunity (CMI) at baseline and at different time points after transplantation was assessed using an interferon γ enzyme-linked immunosorbent spot assay., Results: rATG increased the risk of CMV DNAemia in R+ but not in D+R- KTRs. In R+ CMI-positive (CMI+) patients, the CMV DNAemia rate was higher in rATG-treated than in anti-IL-2RA-treated patients; no difference was observed among R+ CMI-negative (CMI-) patients. Longitudinal follow-up demonstrated a deeper depletion of preformed CMV CMI in R+ rATG-treated patients., Conclusions: D+R- KTRs have the highest risk of CMV DNAemia, but rATG adds no further risk. Among R+ KTRs, we described 3 groups, the least prone being R+CMI+ KTRs without rATG, then R+CMI+ KTRs with rATG, and finally R+CMI- KTRs. CMV serostatus, baseline CMV-specific CMI, and induction therapy may lead to personalized preventive therapy in further studies., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)