Contexte : les mitochondries assurent la regulation des especes reactives de l’oxygene, la survie cellulaire, l’apoptose et la production d’energie. Ces fonctions sont controlees par des genes de l’ADN mitochondrial et nucleaire. Les variants pathogenes affectant ceux-ci vont donc etre responsables de mitochondriopathies primitives (MIDs), qui peuvent etre diagnostiquees a l’âge adulte. Les fonctions renales dependent de la respiration mitochondriale. Cependant, la prevalence des nephropathies associees aux MIDs (MIDANs) est inconnue dans la population adulte. Methodologie : les adultes (>16 ans) avec un diagnostic moleculaire de MID entre 2000 et 2020, et avec une evaluation de maladie renale (MR), etaient inclus dans l’etude retrospective. Les MIDANs etaient definies par l’association d’une MID et d’une MR. Les caracteristiques phenotypiques, biologiques, histologiques et genotypiques etaient recueillies a partir des dossiers medicaux. Resultats : nous avons inclus 80 adultes avec MID et confirme la presence de MIDAN chez 28/80 (35%). Dans cette population, 14/28 (50%) des MR etaient identifiees avant l’etude. Les MIDANs etaient essentiellement des nephropathies tubulo-interstitielles (TIN) avec 14/28 (50%) et des nephropathies glomerulaires (GD) avec 9/28 (32,1%) des MIDANs. Les MIDANs etaient independamment associees avec une albumine elevee [odds ratio (OR), 0.79; 95% intervalle de confiance (95%IC), 0.67–0.95], l’hypertension arterielle (OR, 4.23; 95%IC, 1.04-17.17) et les anomalies de la vision (OR, 0.17; 95%IC, 0.03–0.94). Nous n’avons pas mis en evidence d’association entre les MIDANs, les donnees histologiques et genotypiques. Conclusion : les MIDANs sont frequentes et sous-estimees chez les adultes avec MIDs. Ce sont essentiellement des TIN et des GD. Les anomalies de la vision, l’hypertension arterielle et l’albuminemie etaient independamment associes avec les MIDANs. Notre etude ouvre la voie a des etudes prospectives, evaluant notamment la prevalence des MIDANs au sein d’une population de MR indeterminees.
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.
T‐cell mediated rejection (TCMR), de novo anti‐HLA donor‐specific antibodies ( dn DSAs) and ensuing antibody‐mediated rejection (ABMR) reduce kidney transplantation (KT) survival. The immunomodulatory effects of 25‐hydroxyvitamin D [25(OH)D] could be beneficial for KT outcomes. We aimed to evaluating the association between 25(OH)D levels, the development of dn DSAs, clinical TCMR and ABMR, and graft survival. This single center retrospective study included 253 KT recipients (KTRs) transplanted without preformed DSA between 2010 and 2013. We measured 25(OH)D in successive serum samples: at KT (M0) and M12 for the entire cohort, and additionally at M24 and/or M36 when sera were available. We assessed graft outcomes up to 5 years post‐KT. The proportion of KTRs having sufficient 25(OH)D at KT (M0) was high (81.4%) and then dropped at M12 (71.1%). KTRs with sufficient 25(OH)D at M0 experienced less clinical TCMR (HR, 0.41; 95% CI, 0.19–0.88 in multivariate analysis). A sufficient 25(OH)D at M12 was independently associated with a longer dn DSA‐free survival (HR, 0.34; 95% CI, 0.17–0.69). There was no association between 25(OH)D and clinical AMBR. Studying the KTRs with 25(OH)D measurements at M12, M24 and M36 ( n = 203), we showed that 25(OH)D sufficiency over the 3 first‐years post‐KT was associated with a longer graft survival in multivariate analyses (HR, 0.39; 95% CI, 0.22–0.70). To our knowledge, this study is the first showing an association between 25(OH)D sufficiency post‐KT and dn DSA occurrence in KTRs. Moreover, we reinforce previously published data showing an association between 25(OH)D, TCMR and graft survival in KT.
ABSTRACT Background Mitochondrial functions are controlled by genes of both mitochondrial and nuclear DNA. Pathogenic variants affecting any of these are responsible for primary mitochondrial disorders (MIDs), which can be diagnosed during adulthood. Kidney functions are highly dependent on mitochondrial respiration. However, the prevalence of MID-associated nephropathies (MIDANs) is unknown in the adult population. We aimed to address this point and to provide a full characterization of MIDANs in this population. Methods We retrospectively included for observational study adults (≥16 years of age) with genetically diagnosed MID between 2000 and 2020 in our tertiary care academic centre when they had a chronic kidney disease (CKD) evaluation. MIDANs were ascertained by CKD occurring in MIDs. The phenotypic, biological, histopathological and genotypic characteristics were recorded from the medical charts. Results We included 80 MID-affected adults and ascertained MIDANs in 28/80 (35%). Kidney diseases under the care of a nephrologist occurred in only 14/28 (50%) of the adults with MIDAN. MIDANs were tubulointerstitial nephropathy in 14/28 patients (50%) and glomerular diseases in 9/28 (32.1%). In adults with MID, MIDAN was negatively associated with higher albumin levels {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.67–0.95]} and vision abnormalities [OR 0.17 (95% CI 0.03–0.94)] and positively associated with hypertension [OR 4.23 (95% CI 1.04–17.17)]. Conclusion MIDANs are frequent among adult MIDs. They are mostly represented by tubulointerstitial nephropathy or glomerular disease. Vision abnormalities, hypertension and albumin levels were independently associated with MIDANs. Our results pave the way for prospective studies investigating the prevalence of MIDANs among undetermined kidney disease populations.
