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Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.

Background Muscle wasting is observed in the course of many diseases and also during physiological conditions (disuse, ageing). Skeletal muscle mass is largely controlled by the ubiquitin‐proteasome system and thus by the ubiquitinating enzymes (E2s and E3s) that target substrates for subsequent degradation. MuRF1 is the only E3 ubiquitin ligase known to target contractile proteins (α‐actin, myosins) during catabolic situations. However, MuRF1 depends on E2 ubiquitin‐conjugating enzymes for ubiquitin chain formation on the substrates. MuRF1‐E2 couples are therefore putative targets for preventing muscle wasting. Methods We focused on 14 E2 enzymes that are either expressed in skeletal muscle or up‐regulated during atrophying conditions. In this work, we demonstrated that only highly sensitive and complementary interactomic approaches (surface plasmon resonance, yeast three‐hybrid, and split green fluorescent protein) allowed the identification of MuRF1 E2 partners. Results Five E2 enzymes physically interacted with MuRF1, namely, E2E1, E2G1, E2J1, E2J2, and E2L3. Moreover, we demonstrated that MuRF1‐E2E1 and MuRF1‐E2J1 interactions are facilitated by telethonin, a newly identified MuRF1 substrate. We next showed that the five identified E2s functionally interacted with MuRF1 since, in contrast to the non‐interacting E2D2, their co‐expression in HEK293T cells with MuRF1 led to increased telethonin degradation. Finally, we showed that telethonin governed the affinity between MuRF1 and E2E1 or E2J1. Conclusions We report here the first MuRF1‐E2s network, which may prove valuable for deciphering the precise mechanisms involved in the atrophying muscle programme and for proposing new therapeutical approaches.

Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass.

Background Tunnelled dialysis catheter (TC) infections are a major health complication and are associated with increased antibiotic consumption, hospital stays, health costs and mortality. Experimental data provide evidence that Ethenox, a mixture of enoxaparine 1000 U/mL in 40% v /v ethanol, could be a promising lock solution. The aim of the study is to compare an interdialytic lock solution of Ethenox with reference lock solutions, unfractionated heparin (UFH) or citrate 4% for the prevention of TCI in hemodialysis patients. Method This study will monitor a multicentre, prospective, single blind, randomized, controlled, parallel group trial. The main inclusion criteria are patients > 18 years old with end-stage renal disease, treated with chronic hemodialysis/hemodiafiltration three times a week, with incident or prevalent non-impregnated internal jugular TCs inserted for at least 2 weeks and able to give informed consent. Exclusion criteria are TCI in the previous 4 weeks and anti-infective treatment for TCI in the previous 2 weeks. Patients will be randomized to receive either study treatment Ethenox in the intervention group or reference solutions in the control group, unfractionated heparin (UFH) or citrate 4% w / v according to usual practice. The primary outcome measure will be time to first TCIs assessed by an endpoint adjudication committee blinded to the study arm according to predefined criteria. Patients will receive the study treatment for up to 12 months. Intention-to-treat analysis of the primary endpoint will be performed with a marginal Cox proportional hazard model. Prospective power calculations indicate that the study will have 90% statistical power to detect a clinical significant two-fold increase in median infection-free survival if 200 patients are recruited into each arm over a period of 24 months. Discussion Firm evidence of the efficacy of the Ethenox lock in preventing TCI could be of major clinical benefit for patients. The results of this study will allow the development of new guidelines based on a high level of evidence. Trial registration ClinicalTrials.gov Identifier: NCT03083184 , date of registration March 17 2017 and European Clinical Trials Database Identifier: EudraCT 2016-A00180-51), date of registration July 11 2016.

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Background There are no easily available markers of renal recovery to guide intermittent hemodialysis (IHD) weaning. The aim of this study was to identify markers for IHD weaning in critically ill patients with acute kidney injury (AKI). Methods We performed a retrospective single-center cohort study of patients treated with IHD for at least 7 days and four dialysis sessions for AKI between 2006 and 2011 in an intensive care unit (ICU) of a French university hospital. Blood and urinary markers were recorded on the day of the last IHD in the ICU for unweaned patients and 2 days after the last IHD for weaned patients. Factors associated with IHD weaning were identified by multiple logistic regression. The areas under the receiver operating characteristic curve (AUROC) and the characteristics of the best diagnostic thresholds were compared. Results Sixty-seven patients were analyzed, including thirty-seven IHD-weaned patients. Urine output [odds ratio (OR) 1.59, 95 % confidence interval (CI) 1.20–2.10 (per ml/kg/24 h increase); P  = 0.01] and urinary urea concentration [OR 1.29, 95 % CI 1.01–1.64 (per 10 mmol/L increase); P  = 0.04] were both associated with IHD weaning. The optimal diagnostic thresholds for IHD weaning were urine output greater than 8.5 ml/kg/24 h, urinary urea concentration greater than 148 mmol/L, and daily urea excretion greater than 1.35 mmol/kg/24 h, with accuracy of 82.1 %, 76.1 %, and 92.5 % ( P  = 0.03), respectively. The AUROC of daily urinary urea excretion (0.96) was greater than the AUROC of urine output (0.86) or the AUROC of urinary urea concentration (0.83) ( P  < 0.001). Conclusions A daily urinary urea excretion greater than 1.35 mmol/kg/24 h was found to be the best marker for weaning ICU patients with AKI from IHD.

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge ( p = NS). The FGR was 62.5% in G1 and 8.1% in G2 ( p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.

Aims The management of chronic kidney disease (CKD) complications is not always adequate in patients with a failed kidney transplant. We aimed to evaluate the frequency of CKD complications and assess whether they may lead to worse outcomes in this patient population. Method We analyzed 49 kidney transplant recipients with a failed transplant (T+) and matched non-transplanted patients (T−) starting dialysis between 2000 and 2010 in five dialysis centers in France. CKD complications at dialysis initiation, hospitalizations and death were recorded and compared between the two groups. Results At dialysis initiation, T+ patients were more likely to have bicarbonate < 22 mmol/l (77.6 vs. 22.0%, p < 0.01), phosphate > 1.5 mmol/l (77.6 vs. 59.2%, p = 0.03), arterial blood pressure > 130/80 mmHg (75.5 vs. 93.9%, p = 0.01), body mass index < 23 (59.2 vs. 32.7%, p = 0.01) and albumin < 38 g/l (69.4 vs. 36.7%) than T− patients. T+ patients were hospitalized more frequently in the year following dialysis initiation (40.8 ± 7.0 vs. 16.3 ± 5.3%, log rank p = 0.01) and 5-year survival rate was lower than in T− patients (82.1 ± 6.2 vs. 64.0 ± 7.4%, log rank p = 0.02). However risk of hospitalization and mortality was lesser after adjustments for CKD complications. Conclusion Despite regular follow-up by nephrologists, CKD complications before initiation of dialysis are more frequent in T+ patients than in T− patients. A better management of CKD complications in T+ patients could improve outcomes after dialysis initiation.

Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40[0.26-0.55] mug/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.

Aims The management of chronic kidney disease (CKD) complications is not always adequate in patients with a failed kidney transplant. We aimed to evaluate the frequency of CKD complications and assess whether they may lead to worse outcomes in this patient population.Method We analyzed 49 kidney transplant recipients with a failed transplant (T+) and matched non-transplanted patients (T-) starting dialysis between 2000 and 2010 in five dialysis centers in France. CKD complications at dialysis initiation, hospitalizations and death were recorded and compared between the two groups.Results At dialysis initiation, T+ patients were more likely to have bicarbonate < 22 mmol/l (77.6 vs. 22.0%, p < 0.01), phosphate > 1.5 mmol/l (77.6 vs. 59.2%, p = 0.03), arterial blood pressure > 130/80 mmHg (75.5 vs. 93.9%, p = 0.01), body mass index < 23 (59.2 vs. 32.7%, p = 0.01) and albumin < 38 g/l (69.4 vs. 36.7%) than T-patients. T+ patients were hospitalized more frequently in the year following dialysis initiation (40.8 +/- 7.0 vs. 16.3 +/- 5.3%, log rank p = 0.01) and 5-year survival rate was lower than in T-patients (82.1 +/- 6.2 vs. 64.0 +/- 7.4%, log rank p = 0.02). However risk of hospitalization and mortality was lesser after adjustments for CKD complications.Conclusion Despite regular follow-up by nephrologists, CKD complications before initiation of dialysis are more frequent in T+ patients than in T-patients. A better management of CKD complications in T+ patients could improve outcomes after dialysis initiation.