25-hydroxyvitamin D sufficiency is associated with lower de novo anti-HLA donor specific antibody and better kidney transplant outcomes.

T-cell mediated rejection (TCMR), de novo anti-HLA donor-specific antibodies (dnDSAs) 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 dnDSAs, 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 dnDSA-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 dnDSA occurrence in KTRs. Moreover, we reinforce previously published data showing an association between 25(OH)D, TCMR and graft survival in KT.

Renal involvement is frequent in adults with primary mitochondrial disorders: an observational study.

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.

Mediterranean Diet for Cardiovascular Risk Reduction in Chronic Kidney Disease.

The Mediterranean diet is a plant-based healthy diet similar to the vegetarian and the Dietary Approaches to Stop Hypertension diets. Unlike vegetarian and Dietary Approaches to Stop Hypertension diets, the Mediterranean diet encourages a lifestyle associated with physical activity, and social connections. In addition, the Mediterranean diet is not based on restriction of nutrients but does limit intake of processed foods. Prospective studies have confirmed that the Mediterranean diet confers primary and secondary cardiovascular disease prevention in the general population. The benefits of the Mediterranean diet lifestyle include reducing the risk of diabetes mellitus, dyslipidemia, and lowers blood pressure. In adults with CKD, adherence to the Mediterranean diet is associated with a lower risk of CKD progression and its complications such as hyperphosphatemia and metabolic acidosis, and reduces production of uremic toxins and inflammatory mediators when compared to omnivore dietary patterns. Nevertheless, prospective studies are needed to confirm the cardiovascular disease prevention with the Mediterranean diet in adults with CKD. Medical nutrition therapy remains a cornerstone of CKD management, and the Mediterranean diet could be utilized to slow CKD progression and complications.

À qui un néphrologue doit-il prescrire un iSGLT2 ? Indications of SGLT2 inhibitors in kidney disease: who, why and when?

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.

Vascularization of Cell-Laden Microfibres by Femtosecond Laser Processing.

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.

Adult onset tubulo-interstitial nephropathy in MT-ND5-related phenotypes.

Kidney is a highly adenosine triphosphate dependent organ in human body. Healthy and functional mitochondria are essential for normal kidney function. Clinical and genetic variability are the hallmarks of mitochondrial disorders. We report here the involvement of two MT-ND5 pathogenic variants encoding for ND5 subunit of respiratory chain complex I, the m.13513G>A and the m.13514A>G, in adult-onset kidney disease in three unrelated patients. The first patient had myopathy encephalopathy lactic acidosis and stroke syndrome, left ventricular hypertrophy with Wolff-Parkinson-White syndrome and tubulo-interstitial kidney disease. The second presented Leber hereditary optic neuropathy associated with tubulo-interstitial kidney disease. The third presented with an isolated chronic tubulo-interstitial kidney disease. These mutations have never been associated with adulthood mitochondrial nephropathy. These case reports highlight the importance to consider mitochondrial dysfunction in tubulo-interstitial kidney disease.