Impact of reference panel composition on scores of script concordance test assessing basic nephrology knowledge in undergraduate medical education.

PURPOSE: In the assessment of basic medical knowledge, the composition of the reference panel between specialists and primary care (PC) physicians is a contentious issue. We assessed the effect of panel composition on the scores of undergraduate medical students in a script concordance test (SCT). METHODS: The scale of an SCT on basic nephrology knowledge was set by a panel of nephrologists or a mixed panel of nephrologists and PC physicians. The results of the SCTs were compared with ANOVA for repeated measurements. Concordance was assessed with Bland and Altman plots. RESULTS: Forty-five students completed the SCT. Their scores differed according to panel composition: 65.6 ± 9.73/100 points for nephrologists, and 70.27 ± 8.82 for the mixed panel, p < 0.001. Concordance between the scores was low with a bias of -4.27 ± 2.19 and a 95% limit of agreement of -8.96 to -0.38. Panel composition led to a change in the ranking of 71% of students (mean 3.6 ± 2.6 places). CONCLUSION: The composition of the reference panel, either specialist or mixed, for SCT assessment of basic knowledge has an impact on test results and student rankings.

Indoxyl sulfate inhibits muscle cell differentiation via Myf6/MRF4 and MYH2 downregulation.

BACKGROUND: Chronic kidney disease (CKD) is associated with a significant decrease in muscle strength and mass, possibly related to muscle cell damage by uremic toxins. Here, we studied in vitro and in vivo the effect of indoxyl sulfate (IS), an indolic uremic toxin, on myoblast proliferation, differentiation and expression of myogenic regulatory factors (MRF)-myoblast determination protein 1 (MyoD1), myogenin (Myog), Myogenic Factor 5 (Myf5) and myogenic regulatory factor 4 (Myf6/MRF4)-and expression of myosin heavy chain, Myh2. METHODS: C2C12 myoblasts were cultured in vitro and differentiated in myotubes for 7 days in the presence of IS at a uremic concentration of 200 µM. Myocytes morphology and differentiation was analyzed after hematoxylin-eosin staining. MRF genes' expression was studied using reverse transcription polymerase chain reaction in myocytes and 5/6th nephrectomized mice muscle. Myf6/MRF4 protein expression was studied using enzyme-linked immunosorbent assay; MYH2 protein expression was studied using western blotting. The role of Aryl Hydrocarbon Receptor (AHR)-the cell receptor of IS-was studied by adding an AHR inhibitor into the cell culture milieu. RESULTS: In the presence of IS, the myotubes obtained were narrower and had fewer nuclei than control myotubes. The presence of IS during differentiation did not modify the gene expression of the MRFs Myf5, MyoD1 and Myog, but induced a decrease in expression of Myf6/MRF4 and MYH2 at the mRNA and the protein level. AHR inhibition by CH223191 did not reverse the decrease in Myf6/MRF4 mRNA expression induced by IS, which rules out the implication of the ARH genomic pathway. In 5/6th nephrectomized mice, the Myf6/MRF4 gene was down-regulated in striated muscles. CONCLUSION: In conclusion, IS inhibits Myf6/MRF4 and MYH2 expression during differentiation of muscle cells, which could lead to a defect in myotube structure. Through these new mechanisms, IS could participate in muscle atrophy observed in CKD.

Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges.

BACKGROUND: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. METHODS: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). RESULTS: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (-15.9%; 95% CI, -29.4 to -2.5) compared with the PLEX not recommended group (-4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. CONCLUSIONS: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.

Mechanisms of myostatin and activin A accumulation in chronic kidney disease.

BACKGROUND: Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance. METHODS: We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells. RESULTS: In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients' muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes. CONCLUSION: During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.

Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study.

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.

No impact of disseminated intravascular coagulation in kidney donors on long-term kidney transplantation outcome: A multicenter propensity-matched study.

The diagnosis of disseminated intravascular coagulation (DIC) is often considered to be a contraindication to organ donation. The aim of this study was to evaluate the impact of DIC+ donors on kidney recipient (KR) evolution. We identified 169 KRs with DIC+ donation after brain death donors between January 1996 and December 2012 in 6 French transplant centers. Individuals were matched using propensity scores to 338 recipients with DIC- donors according to donor age and sex, whether expanded criteria for the donor existed, graft year, and transplantation center. After kidney transplantation, delayed graft function was observed in 28.1% of DIC+ KRs and in 22.8% of DIC- KRs (NS). Renal allograft survival at 1, 5, and 10 years was 94.5%, 89.3%, and 73.9% and 96.2%, 90.8%, and 81.3% in DIC+ KRs and DIC- KRs, respectively (NS). The median estimated glomerular filtration rate (eGFR) was similar between DIC+ and DIC- KRs at 3 months, 1 year, and 10 years: 45.9 vs 48.1 mL/min, 42.1 vs 43.1 mL/min, and 33.9 vs 38.1 mL/min, respectively. Delayed calcineurin inhibitor introduction or induction had no impact on delayed graft function rate or eGFR evolution at 10 years after transplantation in DIC+ KRs. Donor DIC did not seem to affect initial outcome, long-term graft function, or allograft survival.

Evaluation of the efficacy of an interdialytic "ethanol 40% v/v - enoxaparin 1000 U/mL" lock solution to prevent tunnelled catheter infections in chronic hemodialysis patients: a multi-centre, randomized, single blind, parallel group study.

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.

Membranous Nephropathy and Intrarenal Extramedullary Hematopoiesis in a Patient With Myelofibrosis.

Kidney disease in the setting of a hematologic malignancy is common, with the frequency and type of kidney disease varying depending on the specific malignancy. Various glomerular diseases and tumor infiltration of the kidneys have been reported in patients with lymphoproliferative disorders. Descriptions of kidney involvement in myeloproliferative disorders have been much rarer. We report a case of membranous nephropathy accompanied by kidney injury in a patient with primary myelofibrosis with additional features considered related to the patient's myeloproliferative disorder. A 63-year-old patient with primary myelofibrosis underwent kidney biopsy to investigate nephrotic-range proteinuria and reduced kidney function. Histologic analysis revealed mesangial sclerosis and hypercellularity, changes indicative of membranous nephropathy, and infiltration of hematopoietic cells into the renal interstitium, peritubular capillaries, and perirenal tissue consistent with extramedullary hematopoiesis. He was treated with renin-angiotensin blockade and a Janus kinase inhibitor, resulting in improvement in kidney function and proteinuria.

Bile Cast Nephropathy Caused by Obstructive Cholestasis.

Acute kidney injury (AKI) is a major complication in patients with liver disease. Although hepatorenal syndrome is frequently involved, bile cast nephropathy, characterized by tubular bile cast formation, has been scarcely described in the setting of severe liver failure. Few renal histology studies are available in these patients. We describe a case of bile cast nephropathy in a patient with obstructive cholestasis caused by stones in the common bile duct. The kidney biopsy confirmed this diagnosis, with several green casts in tubular lumens, tubular injury, and bilirubin composition of the tubular casts with Hall stain. The patient had no confounding cause of kidney failure, and complete kidney recovery followed removal of the bile duct obstruction. This case shows that severe cholestasis is sufficient to cause AKI, and that AKI can be reversible after treatment of the biliary obstruction.

Daily urinary urea excretion to guide intermittent hemodialysis weaning in critically ill patients.

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.

Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group.

The use of plasma exchanges (PLEX) in systemic necrotizing vasculitides (SNV) still need to be codified. To describe indications, efficacy and safety of PLEX for the treatment of SNV, we conducted a multicenter retrospective study on patients with ANCA-associated vasculitis (AAV) or non-viral polyarteritis nodosa (PAN) treated with PLEX. One hundred and fifty-two patients were included: GPA (n = 87), MPA (n = 56), EGPA (n = 4) and PAN (n = 5). PLEX were used for rapidly progressive glomerulonephritis (RPGN) in 126 cases (86%), alveolar hemorrhage in 64 cases (42%), and severe mononeuritis multiplex in 23 cases (15%). In patients with RPGN, there was a significant improvement in renal function compared to baseline value (P < 0.0001), the plateau being reached at month 3 after PLEX initiation, and estimated glomerular filtration rate improved especially as the number of PLEX increased. In patients with alveolar hemorrhage, mechanical ventilation was discontinued in all patients after a median time of 15 days. Patients treated for mononeuritis multiplex showed improvement of severe motor weakness. After a median follow of 22 months, 18 deaths (12%) were recorded, mainly in patients with RPGN and within the first 6 months. Incidence of end-stage renal disease and/or death was similar between groups of different baseline renal function, but was increased in MPO-ANCA compared to PR3-ANCA. Adverse events attributable to PLEX were recorded in 63%. No death occurred during PLEX. This large series describes indications, efficacy and safety of PLEX in daily practice. Randomized controlled studies are ongoing to define optimal indications, PLEX regimen and concomitant medications.

Safe use of citric acid-based dialysate and heparin removal in postdilution online hemodiafiltration.

BACKGROUND: Anticoagulation of the blood circuit with heparin is essential for hemodialysis, but exposes patients to several risks (bleeding, thrombocytopenia, etc.). The use of citric acid-based dialysate (CitA-D) allows the reduction of heparin in conventional hemodialysis. We evaluated the feasibility of using CitA-D in postdilution online hemodiafiltration (OL-HDF) and of removing heparin. METHODS: We prospectively compared chlorhydric acid-based dialysate with CitA-D in 10 patients treated by OL-HDF. First, we reduced heparin by half the dose and then we totally removed anticoagulation. RESULTS: For all 120 sessions using heparin-free CitA-D, only one clotting episode related to an arteriovenous fistula stenosis was observed. No adverse clinical effect was observed. (Kt/V)sp, predialytic serum bicarbonate, calcium, phosphate, parathroid hormone, and ß2-microglobulin remained the same in all cases. CONCLUSION: Our data suggest that the use of CitA-D in OL-HDF is safe and allows heparin removal in most patients.

Innovations thérapeutiques dans la prise en charge de l'anémie de la maladie rénale chronique Therapeutic innovations in the management of chronic kidney disease-associated anemia.

Anemia is a common complication of chronic kidney disease (CKD). The insufficient erythropoietin (EPO) production by the kidneys and iron deficiency are the main causes. Iron supplementation and the administration of recombinant EPO are the main treatment modalities. New iron formulations that can be administered orally, intravenously or directly via the dialysate have recently been developed to improve efficacy and tolerance. Ferric citrate administered orally can effectively corrects anemia in case of iron deficiency and in addition chelate phosphate in the gut lumen. Ferric carboxymaltose allows intravenous administration of larger doses given less frequently. Ferric pyrophosphate citrate administered directly via the dialysate allows the compensation of iron losses during the hemodialysis session. HIF-prolyl-hydroxylase inhibitors are a new therapeutic class of erythropoiesis-stimulating agents. Orally administered, they act by stabilizing the HIF transcription factor involved in the initiation of erythropoietin production by hypoxia. Several clinical studies have recently evaluated these new molecules in comparison with recombinant EPO. In CKD patients not yet on dialysis or undergoing dialysis therapy non-inferiority in correcting anemia has been demonstrated compared with recombinant EPO. The decrease in circulating hepcidin they induce appears greater than that induced by injectable recombinant EPO. Presently available reports on the safety of HIF-prolyl-hydroxylase inhibitors are reassuring but need to be confirmed in longer-term studies of larger size. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation.

[Evaluation of serum iron as a predictor of a hemoglobin response to injectable iron treatment in chronic hemodialysis patients]. / Évaluation du fer sérique comme facteur prédictif d'une réponse de l'hémoglobine au traitement par fer injectable chez les patients hémodialysés chroniques.

BACKGROUND: The detection and correction of iron deficiency are essential for the treatment of anemia in chronic hemodialysis patients. The aim of our study was to assess the ability of serum iron to predict hemoglobin response to intravenous iron supplementation in hemodialysis patients. METHODS: It is a retrospective study in 91 hemodialysis patients during 2016 at Clermont-Ferrand University Hospital for whom intravenous iron supplementation had been started. A responder patient was defined as an increase in hemoglobin greater than or equal to 1 g/dL/month and/or a decrease in the dose of erythropoiesis stimulating agent after two months of iron supplementation. RESULTS: In responding patients, serum iron was significantly lower (6.7 ± 2.7 µmol/L) compared to non-responding patients (8.9±2.9 µmol/L; P<0.001). The positive response to iron supplementation was significantly associated with low serum iron (odds ratio = 0.58 [0.42-0.81]; P=0.002) in a logistic regression model taking into account ferritin, transferrin saturation coefficient, dose variation monthly iron and erythropoiesis stimulating agent and the duration of dialysis. The area under the receiver operating characteristic curve of serum iron, ferritin and transferrin saturation coefficient to predict the response to iron supplementation were 0.72, 0.51 and 0.64, respectively (serum iron versus ferritin [P=0.006] and serum iron versus transferrin saturation coefficient [P=0.04]). The sensitivity for serum iron below 7.5 µmol/L was better than that for ferritin below 86 ng/mL (P<0.001) and the specificity for serum iron below 7.5 µmol/L was better than that for TSC less than 19% (P=0.02). CONCLUSION: Serum iron below 7.5 µmol/L can predict the success of the response to iron supplementation in chronic hemodialysis patients.

Management of Immunosuppression After Kidney Transplant Failure: Effect on Patient Sensitization.

BACKGROUND: Immunosuppressive treatment is often interrupted in the first months following kidney transplant failure (KTF) to limit side effects. The aim of this study was to assess the effect of prolonged treatment (PT) of more than 3 months' duration after KTF on HLA sensitization and treatment tolerance. METHODS: We performed a retrospective observational study involving 119 patients with KTF in 3 French kidney transplant centers between June 2007 and June 2017. Sensitization was defined as the development of HLA donor-specific antibodies (DSA). RESULTS: In the PT group receiving calcineurin inhibitor (CNI) treatment, 30 of 52 patients (57.7%) were sensitized vs 52 of 67 patients (77.6%) who had early cessation of treatment (P = .02). The results were confirmed by multivariate analysis (odds ratio [OR] = 0.39, 95% confidence interval [CI] [0.16; 0.98], P = .04). The development of de novo DSAs after CNI treatment (n = 63/90 [70.0%]) was significantly more frequent than during CNI treatment, (n = 18/52 [34.6%], P = .01). Panel-reactive antibody ≥85% was lower in the PT group in multivariate analysis (OR = 0.28, 95% CI [0.10; 0.78], P = .02). No differences in the rates of infection, cardiovascular complications, neoplasia, and deaths were observed between the 2 groups. In multivariate analysis, continuation of corticosteroid treatment had no influence on sensitization but was associated with a higher rate of infection (OR = 2.66, 95% CI [1.09; 6.46], P = .03). CONCLUSION: Maintenance of CNI treatment after return to dialysis in patients requesting a repeat transplant could avoid the development of anti-HLA sensitization with a good tolerance.

Day and night changes in energy expenditure of patients on automated peritoneal dialysis.

RATIONALE: Automated peritoneal dialysis (APD) treatment for end-stage kidney disease affords patients a degree of autonomy in everyday life. Clinical investigations of their energy expenditure (EE) are usually based on resting EE, which could mask day and night variations in EE. The aim of this study, therefore, was to compare the components of EE in APD patients and healthy control (C) subjects. MATERIAL AND METHOD: Patients treated with APD for more than 3 months were compared with C volunteers matched for age and lean body mass (LBM). Biochemical analyses were performed and body composition was determined by DEXA to adjust EE to LBM. Total EE, its different components and respiratory quotients (RQ) were measured by a gas exchange method in calorimetric chambers. Spontaneous total and activity-related EE (AEE) were also measured in free-living conditions over 4 days by a calibrated accelerometer and a heart rate monitor. RESULTS: APD (n = 7) and C (n = 7) patients did not differ in age and body composition. REE did not differ between the two groups. However, prandial increase in EE adjusted for dietary energy intake was higher in APD patients (+57.5 ± 12.71 kcal/h) than in C subjects (+33.8 ± 10.5 kcal/h, p = 0.003) and nocturnal decrease in EE tended to be lower in APD patients undergoing dialysis sessions (- 4.53 ± 8.37 kcal/h) than in subjects (- 11.8 ± 7.69 kcal/h, p = 0.059). Resting RQ (0.91 ± 0.09 vs 0.81 ± 0.04, p = 0.032) and nocturnal RQ (0.91 ± 0.09 vs 0.81 ± 0.04, p = 0.032) were significantly higher in APD patients, indicating a preferential use of glucose substrate potentially absorbed across the peritoneum. AEE was lower in APD patients (595.9 ± 383.2 kcal/d) than in C subjects (1205.2 ± 370.5 kcal/d, p = 0.011). In contrast, energy intakes were not significantly different (1986 ± 465 vs 2083 ± 377 kcal/d, p = 0.677). CONCLUSION: Although the two groups had identical resting EE, APD patients had a higher prandial increase in EE, a lower activity-related EE and higher resting and nocturnal RQ than healthy subjects.

Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

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] µg/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.

Systematic Review of Atrial Vascular Access for Dialysis Catheter.

INTRODUCTION: The last decade has seen a steady increase worldwide in the prevalence of end-stage renal disease (ESRD). Hemodialysis is the major modality of renal replacement therapy (RRT) in 70% to 90% of patients, who require well-functioning vascular access for this procedure. The recommended access for hemodialysis is an arteriovenous fistula or a vascular graft. However, recourse to central venous catheters remains essential for patients whose chronic renal disease is diagnosed at the end stage or in whom an arteriovenous fistula cannot be created or maintained. Tunneled dialysis catheter (TDC) exposure can induce venous stenosis and occlusions and can result in superior vena cava syndrome and/or vascular access loss. Exhaustion of conventional vascular accesses is 1 of the greatest challenges that nephrologists and patients have to face. Several unconventional salvage-therapy routes for TDC placement in patients with exhausted upper body venous access have been reported in the literature. METHODS: We report 2 new cases of intra-atrial TDC placement for patients with exhausted vascular access and perform a meta-analysis of cases from the literature. RESULTS: A total of 51 patients were included. The TDC was inserted by a cardiovascular surgeon in all cases. At the end of follow-up, 75% patients were alive. The median survival time was 25 months. Survival time of hemodialysis patients with intra-atrial TDC was lower than that observed with conventional TDC. CONCLUSIONS: This unconventional technique is safe and functional for hemodialysis patients with exhausted venous access. Atrial vascular access for TDC placement is salvage therapy and is therefore potentially lifesaving.

Renal Transplant in Obese Patients and Impact of Weight Loss Before Surgery on Surgical and Medical Outcomes: A Single-Center Cohort Study.

OBJECTIVES: Previous studies have linked obesity to poor outcomes in renal transplant recipients, prompting many transplant centers to encourage weight loss pretransplant in obese patients. Here, we performed a single-center retrospective study to assess the effects of weight loss on graft and patient outcomes. MATERIALS AND METHODS: Data from 893 renal transplant recipients at our center from 2007 to 2011 were analyzed. First, renal transplant recipients with a history of obesity before transplant (42%) were compared with nonobese patients. Second, in the obese group, renal transplant recipients with significant weight loss (> 10%) before transplant were compared with other obese renal transplant recipients without significant weight loss. RESULTS: Renal transplant recipients were predominantly white, with 74% having undergone living-donor transplant. Obese patients were older (56.6 vs 46.7 y old) and had more comorbidities and more surgical complications, in particular wound complications and incisional hernias, posttransplant than nonobese patients (14.7 vs 5.5%, respectively). Patient and graft survival rates were similar to those in nonobese patients. In the obese group, patient characteristics and medical or surgical complications after transplant did not differ between those with or without significant weight loss. However, obese patient and graft survival rates were lower in patients with weight loss than in obese patients without weight loss. CONCLUSIONS: In our study, weight loss before transplant surgery in obese patients had no influence on surgical outcomes but was associated with a higher mortality rate. A prospective assessment of the impact of weight loss before surgery is needed to establish its usefulness.