Julien Aniort

A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate: Characterization of MuRF1-E2 network

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.

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.

Upregulation of MuRF1 and MAFbx participates to muscle wasting upon gentamicin-induced acute kidney injury.

Acute Kidney Injury (AKI) is frequently encountered in hospitalized patients where it is associated with increased mortality and morbidity notably affecting muscle wasting. Increased protein degradation has been shown to be the main actor of AKI-induced muscle atrophy, but the proteolytic pathways involved are poorly known. The Ubiquitin Proteasome System (UPS) is almost systematically activated in various catabolic situations, and the E3 ligases MuRF1 and MAFbx are generally up regulated in atrophying muscles. We hypothesized that the UPS may be one of the main actors in catabolic skeletal muscles from AKI animals. We used gentamicin-induced acute kidney disease (G-AKI) in rats fed a high protein diet to promote acidosis. We first addressed the impact of G-AKI in the development of mild catabolic conditions. We found that both muscle atrophy and UPS activation were induced with the development of G-AKI. In addition, the phasic muscles were more sensitive to 7-days G-AKI (-11 to -17%, P<0.05) than the antigravity soleus muscle (-11%, NS), indicating a differential impact of AKI in the musculature. We observed an increased expression of the muscle-specific E3 ligases MuRF1 and MAFbx in phasic muscles that was highly correlated to the G-AKI severity (R2=0.64, P<0.01 and R2=0.71, P<0.005 respectively). Conversely, we observed no variation in the expression of three other E3 ligases (Nedd4, Trim32 and Fbxo30/MUSA1). Altogether, our data indicate that MuRF1 and MAFbx are sensitive markers and potential targets to prevent muscle atrophy during G-AKI.

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.

Immunoallergic interstitial nephritis secondary to denosumab

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 25 fevrier 2017

Chronic renal failure complications and management in kidney transplanted and nontransplanted patients.

BACKGROUND Our purpose was to compare the management of chronic kidney disease (CKD) according to Kidney Disease Quality Initiative (K/DOQI) recommendations in kidney transplanted patients (T) and nontransplanted ones (NT). METHODS Data concerning CKD complications were collected retrospectively. Patients seen in consultations in our department from May 2009 to June 2010 were selected if they had at least 6 months of follow-up, CKD stage 4 or 5, and no exclusion criteria namely hospitalization, active cancer, or infection in the 3 months before data collection. RESULTS Fifty-eight T were compared with 85 NT matched by CKD stage (4-5). Anemia within K/DOQI target was better controlled among NT (51.2% versus 41.3%); however, ferritin levels within K/DOQI target were higher (80% T versus 51.7% NT). Average arterial blood pressure was similar in both groups but 51.7% of T were in K/DOQI target versus 41% of NT. Dyslipidemia within cholesterol K/DOQI target was better controlled in 60% (NT) versus 35% NT with 63.5% versus 38% NT within low-density lipoprotein K/DOQI targets. Phosphorus level was better controlled among T; parathyroid was better controlled in among 65% NT versus 50% T within the target level. CONCLUSION Most complications of CKD were better managed among NT.