Outcomes of kidney transplant recipients who underwent pre-transplant bariatric surgery for severe obesity: a long-term follow-up study.

BACKGROUND: Kidney transplantation (KT) is the preferred therapy for end-stage renal disease (ESRD). While a major cause for ESRD, obesity is also a key obstacle to candidacy for KT. Bariatric surgery, particularly sleeve gastrectomy (SG), is increasingly used to improve access to KT in patients with obesity, but the literature especially on outcomes post-KT remains lacking. We aimed to provide a long-term follow-up analysis of efficacy and outcomes of a previously described cohort of patients with obesity, who had SG as a means for access to KT. METHODS: This is a single-center retrospective follow-up study of 32 patients with advanced chronic kidney disease or ESRD, who were referred and underwent SG between 2013 and 2018 as an access strategy to KT. The primary outcome was successful KT. Ninety-day outcomes, long-term graft function, and changes in weight and obesity-related comorbidities after KT were assessed. Descriptive statistics are presented as count (percentage) or median (interquartile range). RESULTS: At baseline, 18 (56%) were male with a median age and BMI of 51 (11) years and 42.3 (5.2) kg/m2, respectively. Median follow-up time post-SG was 53 (58) months. At last follow-up, 23 (72%) patients received KT. Median time to KT was 16 (20) months and BMI was 34.0 (5.1) kg/m2 at time of transplant. At KT, 13 (57%) and 20 (87%) had diabetes and hypertension, respectively. Median follow-up post-KT was 16 (47) months. There was one graft loss requiring return to dialysis. At 5-year post-KT, median serum creatinine was 136 (66) µmol/l. At last follow-up post-KT, median BMI remained at 33.7 (7.6) kg/m2. Among patients with diabetes and hypertension, 7/13 (54%) and 5/20 (25%) had either improvement or remission of their comorbidities, respectively. CONCLUSION: SG is an effective strategy to improve access to KT in patients with severe obesity. Transplant recipients also continue to benefit from sustained weight loss and improved related comorbidities that may positively impact their graft function after KT.

MCAM+ brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4+ T lymphocytes.

The trafficking of autoreactive leucocytes across the blood-brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood-brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinflammation remains understudied. Here, we show that Mcam identifies inflammatory brain endothelial cells with pro-migratory transcriptomic signature during experimental autoimmune encephalomyelitis. In addition, MCAM was preferentially upregulated on blood-brain barrier endothelial cells in multiple sclerosis lesions in situ and at experimental autoimmune encephalomyelitis disease onset by molecular MRI. In vitro and in vivo, we demonstrate that MCAM on blood-brain barrier endothelial cells contributes to experimental autoimmune encephalomyelitis development by promoting the cellular trafficking of TH1 and TH17 lymphocytes across the blood-brain barrier. Last, we showcase ST14 as an immune ligand to brain endothelial MCAM, enriched on CD4+ T lymphocytes that cross the blood-brain barrier in vitro, in vivo and in multiple sclerosis lesions as detected by flow cytometry on rapid autopsy derived brain tissue from multiple sclerosis patients. Collectively, our findings reveal that MCAM is at the centre of a pathological pathway used by brain endothelial cells to recruit pathogenic CD4+ T lymphocyte from circulation early during neuroinflammation. The therapeutic targeting of this mechanism is a promising avenue to treat multiple sclerosis.