Bridging the Gap Between CKD Management Paradigms in Transplant and Nontransplant Settings: Published Evidence, Challenges, and Perspectives.

Kidney transplantation (KT) is the best treatment for patients with kidney failure, associated with improved survival and quality of life compared with maintenance dialysis. However, despite constant improvements in the assessment and management of the alloimmune response, KT patients frequently demonstrate a reduced estimated glomerular filtration rate. Therefore, the usual complications of chronic kidney disease (CKD), such as anemia, hypertension, metabolic acidosis, hyperkalemia, or persistent secondary hyperparathyroidism, are highly prevalent after KT. However, their underlying mechanisms are different in the transplant setting (compared with the nontransplanted CKD population), and management recommendations are based on relatively poor-quality data. In recent years, new therapies have emerged, significantly improving kidney and cardiovascular outcomes of non-KT patients with CKD. Whether those new drugs could improve the outcomes of KT patients has largely been under investigated so far. In this review, we will address the challenges of the management of a KT patient with a reduced estimated glomerular filtration rate, cover the published evidence, and highlight the critical knowledge gaps.

Etelcalcetide use During Maintenance Hemodialysis and Incidence of Parathyroidectomy After Kidney Transplantation.

Introduction: Etelcalcetide is an i.v. calcimimetic agent, effectively reducing parathyroid hormone levels in patients on maintenance hemodialysis (HD). The clinical impact of discontinuing etelcalcetide at the time of kidney transplantation is unknown. Methods: We retrospectively reviewed all patients on HD meeting predefined criteria who received a kidney transplant at our institution between January 1, 2015, and December 12, 2022. The incidence of parathyroidectomy and the evolution of calcium, phosphate, and intact parathyroid hormone (iPTH) levels after transplantation was analyzed according to the type of calcimimetic treatment before transplantation (cinacalcet vs. etelcalcetide vs. none). Results: Overall, 372 patients (aged 53 years; interquartile range [IQR]: 42-62 years) were included. At the time of transplantation, 35, 75, and 262 patients were under etelcalcetide, cinacalcet, or no calcimimetic, respectively. After 1064 (IQR: 367-1658) days, the incidences of parathyroidectomy in the etelcalcetide, cinacalcet, no calcimimetic groups were 29%, 12%, and 1%, respectively (P < 0.001). Etelcalcetide was associated with an increased incidence of parathyroidectomy after adjustment for age, sex, and HD vintage (hazard ratio [HR]: 97.0, 95% confidence interval [CI]: 19.1-493.9, P < 0.001). The incidence of parathyroidectomy was related to etelcalcetide dosage (6/11 [54.6%] in patients with ≥ 10 mg vs. 4/24 [16.7%] in patients with < 10 mg, P = 0.02). Moreover, peak calcium levels were higher (P < 0.001) and parathyroidectomy was performed earlier (median 80 vs. 480 days, P < 0.001) in the etelcalcetide compared with the cinacalcet group. Long-term graft function, graft loss, and mortality were similar. Conclusion: Etelcalcetide use during maintenance HD is associated with an increased incidence of early parathyroidectomy after transplantation compared to cinacalcet or no calcimimetic.

Exploring Preservation Modalities in a Split Human Pancreas Model to Investigate the Effect on the Islet Isolation Outcomes.

Background: In islet transplantation, the use of dynamic hypothermic preservation techniques is a current challenge. This study compares the efficacy of 3 pancreas preservation methods: static cold storage, hypothermic machine perfusion (HMP), and oxygenated HMP. Methods: A standardized human pancreas split model was employed using discarded organs from both donation after brain death (n = 15) and donation after circulatory death (DCD) (n = 9) donors. The pancreas head was preserved using static cold storage (control group), whereas the tail was preserved using the 3 different methods (study group). Data on donor characteristics, pancreas histology, isolation outcomes, and functional tests of isolated islets were collected. Results: Insulin secretory function evaluated by calculating stimulation indices and total amount of secreted insulin during high glucose stimulation (area under the curve) through dynamic perifusion experiments was similar across all paired groups from both DCD and donation after brain death donors. In our hands, islet yield (IEQ/g) from the pancreas tails used as study groups was higher than that of the pancreas heads as expected although this difference did not always reach statistical significance because of great variability probably due to suboptimal quality of organs released for research purposes. Moreover, islets from DCD organs had greater purity than controls (P ≤ 0.01) in the HMP study group. Furthermore, our investigation revealed no significant differences in pancreas histology, oxidative stress markers, and apoptosis indicators. Conclusions: For the first time, a comparative analysis was conducted, using a split model, to assess the effects of various preservation methods on islets derived from pancreas donors. Nevertheless, no discernible variances were observed in terms of islet functionality, histological attributes, or isolation efficacy. Further investigations are needed to validate these findings for clinical application.

Donor- and isolation-related predictive factors of in vitro secretory function of cultured human islets.

Background and aims: Human islet preparations designated for research exhibit diverse insulin-secretory profiles. This study aims to assess the impact of donor- and isolation-related factors on in vitro islet secretory function. Methods: A retrospective analysis of 46 isolations from 23 pancreata discarded for clinical transplantation was conducted. In vitro islet secretory function tests were performed on Day 1 and Day 7 of culture. Linear mixed-effects models (LMMs) were employed to investigate the relationships between various predictors characterizing the patient and donor characteristics as well as the isolation effectiveness and two functional outcomes including the islet stimulation index (SI) and area under the insulin curve (AUC). Fixed effects were introduced to represent the main effects of each predictor, and backward elimination was utilized to select the most significant fixed effects for the final model. Interaction effects between the timepoint (Day 7 vs. Day 1) and the predictors were also evaluated to assess whether predictors were associated with the temporal evolution of SI and AUC. Fold-change (Fc) values associated with each predictor were obtained by exponentiating the corresponding coefficients of the models, which were built on log-transformed outcomes. Results: Analysis using LMMs revealed that donor body mass index (BMI) (Fc = 0.961, 95% CI = 0.927-0.996, p = 0.05), donor gender (female vs. male, Fc = 0.702, 95% CI = 0.524-0.942, p = 0.04), and donor hypertension (Fc = 0.623, 95% CI = 0.466-0.832, p= <0.01) were significantly and independently associated with SI. Moreover, donor gender (Fc = 0.512, 95% CI = 0.302-0.864, p = 0.02), donor cause of death (cerebrovascular accident vs. cardiac arrest, Fc = 2.129, 95% CI = 0.915-4.946, p = 0.09; trauma vs. cardiac arrest, Fc = 2.129, 95% CI = 1.112-7.106, p = 0.04), pancreas weight (Fc = 1.01, 95% CI = 1.001-1.019, p = 0.03), and islet equivalent (IEQ)/mg (Fc = 1.277, 95% CI = 1.088-1.510, p ≤ 0.01) were significantly and independently associated with AUC. There was no predictor significantly associated with the temporal evolution between Day 1 and Day 7 for both SI and AUC outcomes. Conclusion: This study identified donor- and isolation-related factors influencing in vitro islet secretory function. Further investigations are essential to validate the applicability of these results in clinical practice.

Tacrolimus Pharmacokinetics is Associated with Gut Microbiota Diversity in Kidney Transplant Patients: Results from a Pilot Cross-Sectional Study.

Clinical use of tacrolimus (TAC), an essential immunosuppressant following transplantation, is complexified by its high pharmacokinetic (PK) variability. The gut microbiota gains growing interest but limited investigations have evaluated its contribution to TAC PKs. Here, we explore the associations between the gut microbiota composition and TAC PKs. In this pilot cross-sectional study (Clinicaltrial.gov NCT04360031), we recruited 93 CYP3A5 non-expressers stabilized kidney transplant recipients. Gut microbiota composition was characterized by 16S rRNA gene sequencing, TAC PK parameters were computed, and additional demographic and medical covariates were collected. Associations between PK parameters or diabetic status and the gut microbiota composition, as reflected by α- and ß-diversity metrics, were evaluated. Patients with higher TAC area under the curve AUC/(dose/kg) had higher bacterial richness, and TAC PK parameters were associated with specific bacterial taxa (e.g., Bilophila) and amplicon sequence variant (ASV; e.g., ASV 1508 and ASV 1982 (Veillonella/unclassified Sporomusaceae); ASV 664 (unclassified Oscillospiraceae)). Building a multiple linear regression model showed that ASV 1508 (co-abundant with ASV 1982) and ASV 664 explained, respectively, 16.0% and 4.6% of the interindividual variability in TAC AUC/(dose/kg) in CYP3A5 non-expresser patients, when adjusting for hematocrit and age. Anaerostipes relative abundance was decreased in patients with diabetes. Altogether, this pilot study revealed unprecedented links between the gut microbiota composition and diversity and TAC PKs in stable kidney transplant recipients. It supports the relevance of studying the gut microbiota as an important contributor to TAC PK variability. Elucidating the causal relationship will offer new perspectives to predict TAC inter- and intra-PK variability.

In situ management of late thrombosis of a renal graft vein in a patient with Cockett syndrome / Prise en charge in situ d'une thrombose tardive de la veine d'un greffon rénal chez une patiente avec un syndrome de Cockett

Late thrombosis of the renal graft vein is a rare complication that results in graft loss in the majority of cases. We describe the case of a 57-year-old female patient who had a kidney transplant 32 years ago and developed a late thrombosis of the graft vein, accompanied by extensive thrombosis in the common femoral and iliac veins. Risk factors included severe malnutrition, chronic inflammation due to an anal fistula, and Cockett syndrome. The treatment consisted of mechanical thrombectomy of the iliac vein, placement of a stent in the common iliac vein, partial thromboaspiration of the renal vein thrombus with local thrombolysis, followed by systemic anticoagulation. With this approach, renal function fully recovered without major complications.

La thrombose tardive de la veine du greffon rénal est une complication rare qui conduit à la perte du greffon dans la majorité des cas. Nous présentons le cas d'une femme de 57 ans, transplantée depuis 32 ans, qui a développé une thrombose de la veine du greffon, se manifestant par une insuffisance rénale aiguë anurique. Cette thrombose compliquait une thrombose extensive débutant dans la veine fémorale superficielle et s'étendant dans les veines fémorale commune et iliaque. La patiente présentait plusieurs facteurs de risque de thrombose veineuse, tels qu'un état de malnutrition sévère, une inflammation chronique due à une fistule anale chronique et un syndrome de Cockett. La patiente a été traitée en plusieurs étapes successives : une thrombectomie mécanique de toute la veine iliaque a d'abord été réalisée, suivie de la mise en place d'un stent dans la veine iliaque commune gauche en raison du syndrome de Cockett, puis d'une thrombo-aspiration partielle du thrombus de la veine rénale combinée à une thrombolyse locale (par urokinase) de la veine rénale via un cathéter, et enfin d'une anticoagulation systémique. Cette approche a permis une récupération complète de la fonction rénale sans complication notable. Nous rapportons cette prise en charge in situ d'une thrombose tardive de la veine d'un greffon rénal chez une patiente avec un syndrome de Cockett, ayant permis une issue favorable.

Impact of thrice-weekly cotrimoxazole prophylaxis on creatinine and potassium plasma levels in kidney transplant recipients.

INTRODUCTION: Cotrimoxazole (CTX) 800/160 mg daily or thrice-weekly is recommended as prophylaxis of Pneumocystis jirovecii pneumonia in kidney transplant recipients. Cotrimoxazole 800/160 daily elevates plasma creatinine and potassium levels but whether the thrice-weekly regimen does so is unknown. METHODS: Medical records of 225 kidney transplant recipients at Cliniques Universitaires Saint-Luc were analyzed retrospectively. All received thrice-weekly CTX 800/160 for 6 months after transplantation. Monthly laboratory results, co-medications, and tacrolimus trough levels were compared. Standard statistical tests were used. RESULTS: One month after CTX stop, creatinine level decreased by 0.11 mg/dl (8%, p = 0.029). This contrasts with its stability in previous and subsequent months. No co-medication change accounted for this decrease. The decrease averaged 0.17 mg/dl (p < 0.01) in the highest initial creatinine tertile. The higher the initial creatinine level, the greater the decrease after CTX stop (p < 0.001), and urea levels remained stable after CTX stop. Potassium levels decreased by 0.09 mmol/L (p = 0.021) one month after CTX stop, and decreased by 0.23 mmol/L (p < 0.01) in the highest initial potassium level tertile. CONCLUSIONS: Our study pinpoints the impact of CTX 800/160 thrice-weekly on creatinine and potassium levels in kidney transplant recipients. This should be considered when interpreting the evolution of plasma creatinine over time, especially in patients with graft dysfunction. Thus, creatinine levels of cohorts with 6 months versus lifelong CTX require different interpretations.

Continuous vs. discontinuous purification of isolated human islets: functional and morphological comparison.

Background: The COBE 2991 cell processor, commonly used for pancreatic islet isolation, is no longer distributed in Europe, leading to a search for alternative purification procedures with equivalent efficacy. The aim of this study was to evaluate the efficacy of an alternative method based on the discontinuous purification of islets. Methods: The conventional isolation procedure using a standard continuous islet purification with COBE 2991 of n = 4 human pancreas was compared to n = 8 procedures using a discontinuous purification with a "bottle" method from donors of similar characteristics. Islet equivalents, purity, and dynamic glucose-stimulated insulin secretion were evaluated. Results: A similar islet yield was obtained using continuous vs. discontinuous purification methods (76,292.5 ± 40,550.44 vs. 79,625 ± 41,484.46 islet equivalents, p = 0.89). Islets from both groups had similar purity (78.75% ± 19.73% vs. 55% ± 18.16%, p = 0.08) and functionality both in terms of stimulation index (3.31 ± 0.83 vs. 5.58 ± 3.38, p = 0.22) and insulin secretion (1.26 ± 0.83 vs. 1.53 ± 1.40 mean AUC, p = 0.73). Moreover, the size of the islets was significantly larger in the discontinuous vs. continuous purification group (19.2% ± 10.3% vs. 45.4% ± 18.8% of islets less than 100 µm, p = 0.0097 and 23.7% ± 5.3% vs. 15.6% ± 5.8% of 200-250 µm islet size, p = 0.03). Conclusion: Compared to the conventional purification procedure, discontinuous purification with a bottle method shows similar results with regard to isolation yield and islet secretory function. Furthermore, this alternative technique allows for obtaining larger islets.

Intermittent Surface Oxygenation Results in Similar Mitochondrial Protection and Maintenance of Aerobic Metabolism as Compared to Continuous Oxygenation during Hypothermic Machine Kidney Machine Perfusion.

Short bubble and subsequent surface oxygenation is an innovative oxygenation technique and alternative for membrane oxygenation during hypothermic machine perfusion (HMP). The metabolic effect of the interruption of surface oxygenation for 4 h (mimicking organ transport) during HMP was compared to continuous surface and membrane oxygenation in a pig kidney ex situ preservation model. After 30 min of warm ischemia by vascular clamping, a kidney of a ±40 kg pig was procured and subsequently preserved according to one of the following groups: (1) 22-h HMP + intermittent surface oxygenation (n = 12); (2) 22-h HMP + continuous membrane oxygenation (n = 6); and (3) 22-h HMP + continuous surface oxygenation (n = 7). Brief perfusate O2 uploading before kidney perfusion was either obtained by direct bubble (groups 1, 3) or by membrane (group 2) oxygenation. Bubble oxygenation during minimum 15 min was as efficient as membrane oxygenation in achieving supraphysiological perfusate pO2 levels before kidney perfusion. Metabolic tissue analysis (i.e., lactate, succinate, ATP, NADH, and FMN) during and at the end of the preservation period demonstrated similar mitochondrial protection between all study groups. Short bubble and subsequent intermittent surface oxygenation of the perfusate of an HMP-kidney might be an effective and cheap preservation strategy to protect mitochondria, eliminating the need/costs of a membrane oxygenator and oxygen source during transport.

Peripheral embolism as first and only clinical symptom of a true aneurysmal degeneration of the radial artery after ligation of a radiocephalic fistula.

True aneurysmal degeneration of the inflow artery after arteriovenous fistula ligation is extremely rare. Pain is the most common symptom and surgical treatment by an autologous venous bypass is considered as the treatment of choice with good long-term results. We present a patient with peripheral embolism as first and only symptom leading to the diagnosis of a true aneurysmal degeneration of the entire left radial artery. It was discovered 5 years after the ligation of his radiocephalic fistula. As illustrated by this case, a conservative treatment by antiplatelet and anticoagulation therapy should be considered a satisfying alternative to the standard bypass surgery in patients with anatomical variations (e.g. an incomplete arterial palmar arch) since the latter include a higher risk of postoperative ischemic complications.

First clinical kidney transplantation series using brief bubble and direct surface oxygenation as alternative for membrane oxygenation during hypothermic machine perfusion.

BACKGROUND: Active oxygen during hypothermic machine perfusion has the potential to improve mitochondrial preservation and subsequently decrease the harmful effects of ischemia reperfusion injury. Brief bubble, and subsequent surface oxygenation are an alternative oxygenation technique for membrane-oxygenated kidneys during hypothermic machine perfusion (HMP). METHODS: Between March 20, 2022, and June 13, 2022, 5 kidney grafts originating from 3 donors after circulatory death were oxygenated by bubble and surface oxygenation during HMP. RESULTS: No adverse events related to this new oxygenation technique were observed. All five recipients experienced no dialysis-dependency after transplantation with excellent initial graft function at 3 months after transplantation. CONCLUSIONS: For the first time in human, this new oxygenation technique was successfully applied to 5 HMP-kidneys, originating from donation after circulatory death. If confirmed on larger scale cohorts, this innovative oxygenation technique, as alternative oxygenation technique for membrane-oxygenated kidneys, has the potential to be widely implemented because its simplicity and efficacy, and reducing economic and ecological costs by eliminating the need for a membrane oxygenator and oxygen source during transport.

BRAFV600E Expression in Thyrocytes Causes Recruitment of Immunosuppressive STABILIN-1 Macrophages.

Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers (TC), and BRAFV600E genetic alteration is found in 60% of this endocrine cancer. This oncogene is associated with poor prognosis, resistance to radioiodine therapy, and tumor progression. Histological follow-up by anatomo-pathologists revealed that two-thirds of surgically-removed thyroids do not present malignant lesions. Thus, continued fundamental research into the molecular mechanisms of TC downstream of BRAFV600E remains central to better understanding the clinical behavior of these tumors. To study PTC, we used a mouse model in which expression of BRAFV600E was specifically switched on in thyrocytes by doxycycline administration. Upon daily intraperitoneal doxycycline injection, thyroid tissue rapidly acquired histological features mimicking human PTC. Transcriptomic analysis revealed major changes in immune signaling pathways upon BRAFV600E induction. Multiplex immunofluorescence confirmed the abundant recruitment of macrophages, among which a population of LYVE-1+/CD206+/STABILIN-1+ was dramatically increased. By genetically inactivating the gene coding for the scavenger receptor STABILIN-1, we showed an increase of CD8+ T cells in this in situ BRAFV600E-dependent TC. Lastly, we demonstrated the presence of CD206+/STABILIN-1+ macrophages in human thyroid pathologies. Altogether, we revealed the recruitment of immunosuppressive STABILIN-1 macrophages in a PTC mouse model and the interest to further study this macrophage subpopulation in human thyroid tissues.

Impact of Recipient Obesity on Kidney Transplantation Outcome: A Retrospective Cohort Study with a Matched Comparison.

BACKGROUND: The aim of this study was to evaluate the effect of a recipient's obesity on posttransplant complications and patient and graft survival. METHODS: A single-institution, retrospective study was performed on obese renal transplant recipients (BMI ≥ 30 kg/m2, n = 102) from January 2010 to December 2018, matched with non-obese recipients (BMI < 30 kg/m2, n = 204). For comparison, for every obese patient we selected 2 nonobese patients with a similar age, sex, and period of transplantation. The comparative analysis included patient and graft survival as primary outcomes and graft function and postoperative complications as a secondary outcome. RESULTS: Recipient demographics were comparable in both groups except for diabetic nephropathy in obese patients (P = .0006). Obesity was strongly related to a poorer patient survival (risk ratio [RR] = 2.83 confidence interval [CI] 95% 1.14-7.04; P = .020) but there was no observed difference in graft survival (P = .6). While early graft function was inferior in the obese population (RR = 2.41; CI 95% 1.53-3.79; P = .00016), during late follow-up, no statistically significant differences were observed between both groups (P = .36). Obese recipients had a significantly higher risk of delayed graft function (RR = 1.93; CI 95% (1.19-3.1), P = .0077), heart infarction (RR = 7; CI 95% 1.68-29.26; P = .0042), wound infections (RR = 8; CI 95% 1.96-32.87; P = .0015), diabetes aggravation (RR = 3.13; CI 95% 1.29-7.6; P = .011), and surgical revision for eventration (RR = 8; CI 95% 1.22-52.82; P = .026) when compared with nonobese recipients. CONCLUSIONS: Despite the inferior early kidney graft function in obese recipients, there was no difference observed at the long-term follow-up. However, recipient obesity demonstrated a negative effect on patient survival and postoperative complications.

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival.

BACKGROUND: The lack of space, as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms, remains controversial. AIM: To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease. METHODS: One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without (kidney transplant alone (KTA) group) and 77 with associated ipsilateral nephrectomy (KTIN group), were retrospectively reviewed. Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival. RESULTS: Creation of space for future graft positioning was the main reason (n = 74, 96.1%) for associated ipsilateral nephrectomy. No significant difference in surgical comorbidity (lymphocele, wound infection, incisional hernia, wound hematoma, urinary infection, need for blood transfusion, hospitalization stay, Dindo Clavien classification and readmission rate) was observed between the two study groups. The incidence of primary nonfunction and delayed graft function was comparable in both groups [0% and 2.6% (P = 0.497) and 9.1% and 16.9% (P = 0.230), respectively, in the KTA and KTIN group]. The 1- and 5-year graft survival were 94.8% and 90.3%, and 100% and 93.8%, respectively, in the KTA and KTIN group (P = 0.774). The 1- and 5-year patient survival were 96.1% and 92.9%, and 100% and 100%, respectively, in the KTA and KTIN group (P = 0.168). CONCLUSION: Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short- and long-term graft survival.

Monoclonal Antibody Therapy in Kidney Transplant Recipients With Delta and Omicron Variants of SARS-CoV-2: A Single-Center Case Series.

Rationale & Objective: Neutralizing monoclonal antibody treatments have shown promising preliminary results in kidney transplant recipients infected with severe acute respiratory syndrome coronavirus 2. However, their efficacy in kidney transplant recipients infected with the Omicron variant has not been reported yet. Study Design: Single-center retrospective study. Setting & Participants: We included all consecutive kidney transplant recipients treated with monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 infections (positive polymerase chain reaction on nasopharyngeal swab) between June 10, 2021, and January 14, 2022. Forty-seven kidney transplant recipients were included. All patients had symptoms evolving for ≤7 days and no oxygen therapy need at monoclonal antibody infusion. Results: Symptoms at diagnosis were mainly cough (n = 25; 53%) and fever (n = 15; 32%). Eighty-three percent of the cohort (n = 39) had been vaccinated with at least 2 doses before infection, of whom 30 (77%) had demonstrated a vaccine-induced humoral response. They were treated with either casirivimab-imdevimab (n = 16; 34%) or sotrovimab (n = 31; 66%) a median of 2 days (range, 0-6 days) after the onset of symptoms. Except for 1 mild allergic reaction during casirivimab-imdevimab infusion, no side effects were reported. The median viral loads at admission (day 0) and 7 days after monoclonal antibody infusion were 2,110,027 copies/mL (range, 1,000-153,798,962 copies/mL) and 1,000 copies/mL (range, 0-10,000,000 copies/mL), respectively. Genotypes were available for 22 kidney transplant recipients (47%). Omicron, Delta, and Gamma variants were identified in 13 (59%), 8 (36%), and 1 (5%) patients, respectively. In kidney transplant recipients infected with the Omicron variant, the median viral loads at day 0 and day 7 were 752,789 copies/mL (range, 4,000-12,859,300 copies/mL) and 1,353 copies/mL (range, 0-1,211,163 copies/mL), respectively. 2 kidney transplant recipients required hospitalization immediately after sotrovimab perfusion for oxygen therapy that was weaned in 3 days, allowing patients' discharge. None were admitted to the intensive care unit or died. Limitations: Small sample size, no control group. Conclusions: Neutralizing monoclonal antibody therapy is associated with positive outcomes in kidney transplant recipients with mild coronavirus disease 2019, including those infected with the Omicron variant.

Two miRNAs enriched in plasma extracellular vesicles are potential biomarkers for thyroid cancer.

Differential diagnosis of thyroid cancer and benign nodules is still one of the most challenging issues in the field of endocrinology. To overcome overdiagnosis of papillary thyroid carcinomas (PTC) and the consecutive overtreatment of multinodular diseases, the search for easily accessible, sensitive and accurate biomarkers is critical. Several micro-RNAs (miRNAs) freely circulating in peripheral blood or enclosed in extracellular vesicles (EVs) have been proposed as potential biomarkers from non-invasive liquid biopsies. However, protocols are rarely comparable and conflicting data exist in the literature. In this work, we aimed to assess the diagnostic value of six micro-RNAs by comparing their expression in thyroid tissue to their abundance in bulk plasma and in plasma-EVs, before and after thyroid surgery. Plasma-EVs were isolated using a sequential density- and size-based fractionation, followed by in-depth characterization, confirming EV purity. Micro-RNA levels were measured by RT-qPCR in thyroid tissue, plasma and plasma-EVs. Among the six candidates, only miR-146b-5p and miR-21a-5p displayed a significant differential abundance in purified plasma-derived EVs from patients with PTC and benign disease. However, no difference could be demonstrated in bulk plasma through our cohort of patients. Overall, our work supports the use of a well-defined protocol of plasma-EV miRNAs purification for biomarker discovery, rather than the use of freely circulating miRNAs in bulk plasma. Our work also demonstrates that standardized pre-analytical and analytical procedures as well as optimized EV-miRNAs detection methods are essential.

Pregnancy Outcomes After Kidney Transplantation and Long-Term Evolution of Children: A Single Center Experience.

BACKGROUND: Pregnancies in women who underwent kidney transplants are at high risk compared with the general population. METHODS: In this study, we aimed to retrospectively assess the obstetrical complications, delivery outcomes, and impact of pregnancy on kidney allograft function in a single-center cohort of kidney transplant recipients (KTRs). We provide data regarding the long-term evolution of children. RESULTS: Thirty-two KTRs underwent a total of 57 pregnancies between 1994 and 2010. Fourteen pregnancies (24 %) did not survive caused by miscarriages (n = 9), stillborn (n = 1), ectopic pregnancies (n = 2), and medical abortion (n = 2). Live birth occurred in 76% of pregnancies. Delivery was by cesarean in 66%. The mean gestational age was 30.45 ± 11.3 weeks and 65% of newborns were premature. A low birth weight <2500g was noted in 46%. Obstetric complications were de novo hypertension in 4%, pre-eclampsia in 9%, and gestational diabetes in 2%. The 5- and 10-year post-delivery death-censored graft loss rates were 3.1% and 12.5%, respectively. Data on 21 children were collected via a self-questionnaire. After a median follow-up time of 17 years, they appeared in good medical and psychological health. None of them suffered from chronic disease (especially uronephrological condition) or was taking chronic medication. CONCLUSIONS: Long-term evolution of children born to women who underwent kidney transplants seems favorable. Pregnancies in KTRs are successful in two-thirds of cases but are at increased risk of prematurity, delivery by cesarean, and low birth weight.