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Background The use of a catheter for hemodialysis is associated with a 5-fold increased risk of septicemia. Early detection of catheter-related bloodstrean infection (CRBSI) may decrease morbidity and mortality, but the benefits of systematic blood cultures have not been demonstrated. Materials and methods We retrospectively studied the blood culture results of patients who had been dialyzed with a tunneled jugular catheter for more than 1 month in a dialysis unit from January to December 2015. Systematic monthly catheter blood cultures were taken from the heparin lock solutions in the arterial and venous branches, at the beginning or end of the session. CRBSI was assessed using patient symptoms (fever, chills, hemodynamic instability) and positive catheter blood cultures. Results 75 patients were included. We analyzed the results of 577 systematic catheter blood cultures. 27 (5%) were positive, including 23 from patients who did not develop CRBSI in the following month. For the latter, there was a predominance of coagulase-negative staphylococci. Only four patients with positive catheter blood cultures went on to develop CRBSI in the following month. The sensitivity and specificity of these monthly blood cultures to detect CRBSI in the following month were 0.44 and 0.95, respectively. The positive and negative predictive values of the test were 0.14 and 0.99, respectively. Conclusion In this study, systematic catheter blood cultures did not predict the occurrence of CRBSI. The sensitivity of these tests could be improved by increasing the sampling frequency. A cost-benefit analysis of such measures should be performed.

Background The spectrum of interferon-β (IFN-β)-associated nephropathy remains poorly described and the potential features of this uncommon association remain to be determined. Methods In this study we retrospectively analysed the clinical, laboratory, histological and therapeutic data of patients with biopsy-proven renal disease in a context of IFN-β treatment administered for at least 6 months. Results Eighteen patients (13 women, median age 48 years) with biopsy-proven renal disease occurring during IFN-β therapy were included. The median exposure to IFN-β (14 patients were treated with IFN-β1a and 4 patients with IFN-β1b) was 67 months (range 23–165 months). The clinical presentation consists in hypertension (HT; 83%), malignant HT (44%), proteinuria (protU) >1 g/g (94%), reduced renal function (78%), biological hallmark suggesting thrombotic microangiopathy (TMA; 61%), oedematous syndrome (17%) or nephritic syndrome (11%). The pathological findings included typical features of isolated TMAs in 11 cases, isolated focal segmental glomerulosclerosis (FSGS) lesions in 2 cases and 5 cases with concomitant TMA and FSGS lesions. An exploration of the alternative complement pathway performed in 10 cases (63%) did not identify mutations in genes that regulate the complement system. The statistical analysis highlighted that the occurrence of IFN-β-associated TMA was significantly associated with Rebif, with a weekly dose >50 µg and with multiple weekly injections. In all cases, IFN-β therapy was discontinued. Patients with TMA lesions received other therapies, including corticosteroids (44%), eculizumab (13%) and plasma exchanges (25%). At the end of a 36-month median follow-up, persistent HT and persistent protU were observed in 61% and 22% of patients, respectively. Estimated glomerular filtration rate, Graphical Abstract Graphical Abstract

Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1 mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation. Tacrolimus also affected renal miRNA expression, including miRNAs previously involved in fibrotic and inflammatory processes as "fibromirs" such as miR-21-5p, miR-199a-5p and miR-214-3p. In agreement with in vivo data, Renal Proximal Tubular Epithelial cells exposed to Tacrolimus (25 and 50 µM) showed upregulation of miR-21-5p and the concomitant induction of epithelial phenotypic changes, inflammation and oxidative stress. In conclusion, this study suggests for the first time that miRNAs, especially fibromiRs, participate to Tacrolimus-induced nephrotoxic effects. Therefore, targeting miRNAs may be a new therapeutic option to counteract Tacrolimus deleterious effects on kidney.

Renal fibrosis represents the final stage of most chronic kidney diseases and contributes to the progressive and irreversible decline in kidney function with accumulation of extracellular matrix components in the renal parenchyma. The molecular mechanisms governing the renal fibrosis process are complex and remain poorly understood. Recently, the profibrotic role of several microRNAs (miRNAs) has been described in kidney fibrosis. MiRNAs are a new class of, small non-coding RNAs of about 20 nucleotides that act as gene expression negative regulators at the post-transcriptional level. Seminal studies have highlighted the potential importance of miRNA as new therapeutic targets and innovative diagnostic and/or prognostic biomarkers. This review summarizes recent scientific advances on the role played by miRNAs in kidney fibrogenesis and discusses potential clinical applications as well as future research directions.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established “fibromiRs” involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214-3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three “fibromiRs” involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival.

Introduction La survenue d’une nephropathie sous interferon-beta (IFN-b) est un evenement rare. Quelques cas cliniques et des petites series recentes ont rapporte des microangiopathies thrombotiques (MAT) et des syndromes nephrotiques (SN) au cours du traitement d’une sclerose en plaque par IFN-b. Les objectifs cette etude etaient de decrire les caracteristiques clinicobiologiques, histologiques et pronostiques des nephropathies associees au traitement par IFN-b. Patients/materiels et methodes Nous avons effectue une recherche de cas de nephropathies survenues sous IFN-b aupres des differents centres francais de nephrologie. Une relecture histologique systematique a ete realisee au sein de notre centre. Resultats Nous avons inclus 18 patients ayant presente une nephropathie imputable a un traitement par IFN-b. Le sex-ratio etait de 5 hommes pour 13 femmes et l’âge median de survenue de la nephropathie etait de 47 ans. L’exposition mediane a l’IFN-b etait de 67 mois. La presentation clinique etait heterogene avec une hypertension arterielle (HTA) de novo ou une aggravation d’une HTA (89 % des patients), une HTA maligne (50 %), une proteinurie > 1 g/j (89 %), une insuffisance renale (78 %), une MAT biologique (61 %), un syndrome œdemateux (17 %), ou un SN (11 %). La biopsie renale a ete pratiquee pour 17 patients : 12 presentaient des lesions de MAT glomerulaires et/ou arteriolaires isolees, 2 presentaient des lesions de hyalinose segmentaire et focale (HSF) isolees et 3 presentaient des lesions de MAT et d’HSF. Le patient qui n’a pas eu de biopsie avait presente une MAT biologique avec insuffisance renale et proteinurie sur rein unique. Cinq patients (28 %) ont necessite une prise en charge en soins intensifs avec une hemodialyse initiale chez 3 patients (18 %). Le traitement par IFN-b a ete interrompu chez tous les patients. D’autres therapeutiques avaient ete pratiquees telles qu’une corticotherapie (44 %), de l’eculizumab (17 %) ou une plasmapherese (28 %). Au terme d’un suivi median de 36 mois, une HTA et une proteinurie persistante etaient observees chez respectivement 56 % et 27 % des patients. Il existait une insuffisance renale chronique (IRC) chez 61 % des patients : de stade 3 (44 %) ou de stade 4 (17 %). Aucun patient ne presentait d’IRC terminale. Conclusion Une nephropathie sous IFN-b doit etre recherchee en cas d’HTA et/ou de proteinurie. La presentation initiale est heterogene et non univoque alors qu’histologiquement les lesions de MAT et/ou d’HSF sont observes. Ces nephropathies ressemblent a celles associees aux anti-VEGF, dont des mecanismes physiopathologiques pourraient etre communs. L’interruption precoce de l’IFN-b est indispensable.

Introduction Les lesions de fibrose renales representent une caracteristique commune des maladies renales chroniques et participent, a terme, au developpement d’insuffisance renale chronique terminale. Bien que miR-21 soit un microARN communement implique dans le processus de fibrose renale, les donnees experimentales de la litterature restent contradictoires et suggerent que ce miARN joue un role complexe et ambivalent, protecteur ou deletere, selon le contexte des pathologies renales, aigues ou chroniques. L’objectif de ce travail est de preciser l’implication de miR-21 dans deux modeles murins de nephrotoxicite induite par le tacrolimus et le cisplatine. Patients/materiels et methodes Dans un premier modele, des souris ont ete exposees pendant 28 jours au tacrolimus (1 mg/kg/j). Le second modele repose sur l’utilisation de souris invalidees pour miR-21 exposees au cisplatine de maniere aigue (injection d’une dose unique de 10 mg/kg) ou subaigue (injections repetees de 7 mg/kg de cisplatine). La fonction renale des animaux a ete evaluee. Les reins preleves ont permis de realiser des analyses histologiques et de mesurer l’expression de miR-21, de marqueurs de souffrance renale, d’inflammation et de stress oxydant dans les deux modeles. Resultats Dans le premier modele, les souris exposees au tacrolimus ont une surexpression de miR-21 associee a des lesions renales (surexpression de marqueurs de stress, d’inflammation et fibrotiques). De plus l’expression de miR-21, dans les coupes tissulaires, est localisee au niveau des tubules et dans le compartiment interstitiel, suggerant l’implication de ce dernier dans les lesions de fibrose induites par le tacrolimus. Dans le second modele, les souris ayant recu une injection unique de cisplatine ne presentent pas de difference significative d’uremie, de marqueurs de souffrance renale, d’inflammation et de stress oxydant quel que soit leur statut sauvage ou invalide pour miR-21. En revanche, les injections repetees de cisplatine induisent des lesions renales plus severes chez les souris miR-21-/- que chez les souris sauvages. Conclusion Ces resultats confirment ainsi que miR-21 joue un role ambivalent au cours des lesions renales : protecteur a la phase precoce d’une agression renale aigue et deletere lorsque le processus se prolonge dans le temps. Des etudes complementaires sont necessaires afin d’evaluer l’interet potentiel de miR-21 en tant que cible therapeutique innovante.

Renal fibrosis represents the final stage of most chronic kidney diseases and contributes to the progressive and irreversible decline in kidney function with accumulation of extracellular matrix components in the renal parenchyma. The molecular mechanisms governing the renal fibrosis process are complex and remain poorly understood. Recently, the profibrotic role of several microRNAs (miRNAs) has been described in kidney fibrosis. MiRNAs are a new class of, small non-coding RNAs of about 20 nucleotides that act as gene expression negative regulators at the post-transcriptional level. Seminal studies have highlighted the potential importance of miRNA as new therapeutic targets and innovative diagnostic and/or prognostic biomarkers. This review summarizes recent scientific advances on the role played by miRNAs in kidney fibrogenesis and discusses potential clinical applications as well as future research directions.

Introduction Lors de l’evolution de la maladie de Berger, les lesions de fibrose interstitielle (FI) sont determinantes pour le pronostic renal. Les microARN (miR) sont de petits ARN non codants impliques dans la regulation post-transcriptionnelle. In vitro, et dans des modeles murins de FI, miR-21 et miR-199a-5p ont ete decrits comme pro-fibrosants. Notre objectif est d’analyser le niveau d’expression renale de ces miR chez des patients porteurs d’une maladie de Berger en fonction de leur niveau de FI. Patients et methodes Ce travail a ete mene sur une cohorte de 56 patients porteurs d’une maladie de Berger. Les lesions histologiques ont ete analysees selon la classification d’Oxford (score MEST). Differents grades de FI sont decrits (FI 50 % grade T2 : n = 12). La mesure de l’expression de miR-21 et miR-199a-5p est realisee par une technique de PCR en temps reel a partir du tissu renal. Resultats Le niveau d’expression tissulaire renale de miR-21 augmente de maniere dichotomique des le developpement d’une FI de grade 1 (T0 vs T1 : 1,67 ± 1,6 vs 5,58 ± 3,8, p = 0,001). L’augmentation de miR-199a-5p n’est significative que pour les patients ayant developpe une FI > 50 %. L’analyse de survie actuarielle renale montre l’influence de l’expression renale de miR-21 sur le risque d’evolution vers l’insuffisance renale chronique terminale (risque relatif d’IRCT pour un niveau d’expression renale de miR-21 > 1,93 = 7,3, p = 0,007, IC 95 % : 1,72–31,18). Il n’existe par ailleurs aucune correlation entre le niveau d’expression tissulaire renale de miR-21 et l’existence de lesions glomerulaires actives. Discussion et conclusion Le niveau d’expression tissulaire renale de miR-21 est specifiquement associe au developpement de la FI et au pronostic fonctionnel de la maladie de Berger. MiR-21 pourrait etre une cible therapeutique innovante afin de prevenir le developpement de la FI.