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International audience; Background: Although anti-neutrophil cytoplasmic antibodies [ANCA] are frequently found in patients diagnosed with idiopathic pulmonary fibrosis [IPF], current guidance does not recommend serologic testing for vasculitis. Case presentation: A 71-year old Caucasian male, diagnosed with IPF three years earlier, presented with rapidly progressive glomerulonephritis. ANCA were found both in current and historical sera. A kidney biopsy sample was taken, which revealed a pauci-immune glomerulonephritis, but also areas of glomerular fibrosis, hence strongly suggesting unrecognized flares of an indolent vasculitis in his past. This made the diagnosis of " idiopathic " pulmonary fibrosis very unlikely. Conclusion: As nephrologists, we argue that testing for ANCA should be performed on a systematic basis, at least in elderly patients, even in the absence of extra-pulmonary signs of vasculitis at presentation.

Renal proximal tubular cells are the most energy-demanding cells in the body. The ATP that they use is mostly produced in their mitochondrial and peroxisomal compartments, by the oxidation of fatty acids. When those cells are placed under a biological stress, such as a transient hypoxia, fatty acid oxidation (FAO) is shut down for a period of time that outlasts injury, and carbohydrate oxidation does not take over. Facing those metabolic constraints, surviving tubular epithelial cells exhibit a phenotypic switch that includes cytoskeletal rearrangement and production of extracellular matrix proteins, most probably contributing to acute kidney injury-induced renal fibrogenesis, thence to the development of chronic kidney disease. Here, we review experimental evidence that dysregulation of FAO profoundly affects the fate of tubular epithelial cells, by promoting epithelial-to-mesenchymal transition, inflammation, and eventually interstitial fibrosis. Restoring physiological production of energy is undoubtedly a possible therapeutic approach to unlock the mesenchymal reprograming of tubular epithelial cells in the kidney. In this respect, the benefit of the use of fibrates is uncertain, but new drugs that could specifically target this metabolic pathway, and, hopefully, attenuate renal fibrosis merit future research.

Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.

Epithelial-mesenchymal transition (EMT) is a process by which differentiated epithelial cells undergo a phenotypic conversion and acquire a mesenchymal phenotype, including elongated morphology, enhanced migratory and invasion capacity, and greatly increased production of extracellular matrix (ECM) components. This phenomenon plays a pivotal role in embryonic development, wound healing and tissue regeneration. It has also been involved in organ fibrosis. Some studies suggest that following injury, renal tubular epithelial cells undergo reprograming in mesenchymal cells, and thus constitute an important source of de novo myofibroblasts invading the renal interstitium and contributing to fibrosis. However, an increasing number of studies raise doubts about the existence of this process in vivo. The role of EMT in the development of renal fibrosis remains a matter of intense debate and may depend on the model studied. In this review, we describe the role of EMT in the development of fibrosis of renal graft, and then we propose approaches for detecting and treating renal fibrogenesis by targeting TEM.

Epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs) may participate in the pathogenesis of renal fibrosis. We performed a prospective study of EMT markers in protocol biopsies obtained 3 months after engraftment from 56 patients who received deceased donor kidneys and who had stable renal function. The presence of EMT was examined, and quantified by immunohistochemical staining for vimentin and translocation of beta-catenin to the cytoplasm. EMT status was defined as the presence of EMT markers inor = 10% of TECs. EMT features were virtually absent in implantation biopsies, whereas 41% of the grafts were EMT-positive in the absence of advanced chronic allograft nephropathy. Thirteen patients (23%) had borderline changes or acute rejection. EMT features were more frequent in these patients than in those with normal kidney grafts (vimentin expression, p = 0.003; beta-catenin translocation, p = 0.002). EMT in grafts corresponded with elevated serum creatinine of the donor before the recovery of kidney (p = 0.02) and longer cold ischemia time (p = 0.02). In contrast, the donor age had no influence on the expression of EMT markers. These results suggest that EMT is an early and frequent phenomenon in kidney transplants that could be triggered by immunological and/or ischemic tubular injury.

Background. Mycotic arteritis and/or aneurysms are infrequent complications of renal transplantation. They are mostly secondary to bacterial infection and rarely to Candida albicans. We report four cases of mycotic arteritis due to C. albicans after renal transplantation but which have been inoculated during organ harvesting or conservation. Methods. In all the four cases corresponding to two independent donors, C. albicans was isolated few days later in the systematic culture of the conservative liquid. We also review the clinical features and outcomes of 13 cases previously reported in the literature. Results. In two cases, the diagnosis of fungal arteritis was confirmed only during autopsy after the patient’s death due to massive bleeding. In the other two cases, the diagnosis was made on the arterial section of the anastomotic wall after detransplantation for massive bleeding for arterial leakage although an immediate antifungal treatment with fluconazole and caspofungin was given and was found to be inefficient. Conclusion. This is a serious complication of renal transplantation because it leads to graft loss in the majority of the cases and even to death in a few cases despite an efficient and rapid treatment. Routine fungal cultures of preservation media are important for early diagnosis and timely surgical interventions are life-saving.

Background. The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial cells and are predictive of graft fibrosis. Here, we studied the possible involvement of several major transcriptional regulators, including snail1, phospho-Smad 2/3 and zeb1, in EMT induction in human renal grafts. Methods. We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication. Results. We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ= 0.94, P < 0.0001; vimentin: ρ= 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries. Conclusion. This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss.

Introduction Les pre-eclampsies survenant avant 27 semaines d’amenorrhee (SA) sont souvent fatales pour le fœtus. L’epuration de la forme soluble du recepteur de type 1 du VEGF (sFlt1) est possible par LDL apherese. L’etude ADENA (PHRC regional, NCT02286284 ) a ete concue pour tenter de prolonger la grossesse des patientes en pre-eclampsie severe et tres precoce ( Patients et methodes Etude prospective de phase 2, testant l’effet de seances bi-hebdomadaires de LDL apherese (Kit DALi, Fressenius) via un catheter central chez des patientes adultes, developpant une pre-eclampsie severe avant 26 SA, en l’absence de retard de croissance intra-uterin severe, et de criteres d’accouchement imminent pour sauvetage maternel. Resultats L’etude ADENA a ete suspendue apres l’inclusion de deux patientes, en raison de la futilite de la technique : une amelioration tres transitoire ( Discussion La technique de LDL apherese, prometteuse en l’absence de signes de gravite d’apres une equipe americaine, n’a pas permis d’ameliorer la condition de deux patientes en pre-eclampsie precoce et severe, ni d’epurer suffisamment sFlt1 du sang maternel. Conclusion La LDL apherese ne semble pas appropriee aux patientes ayant une pre-eclampsie tres precoce et severe.

Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Whereas PAI-1 is not expressed in normal kidneys, it is strongly induced in glomerular diseases and thus could promote the local accumulation of fibrin. To study the role of PAI-1 in the development of inflammatory glomerular injury, passive antiglomerular basement membrane (GBM) glomerulonephritis (GN) was induced in PAI-1 knockout mice and in wild-type mice of the same genetic background. Unexpectedly, PAI-1 deficiency was associated with an early and severe exacerbation of glomerular injury: Infiltration by CD4 T cells, proportion of fibrinous crescents, and renal function impairment were significantly more pronounced in PAI-1 -/- mice. Interestingly, activation of transforming growth factor (TGF)- beta, which is known to be dependent on the PA/plasmin system in vitro, was dramatically enhanced in the kidneys in the absence of PAI-1. Moreover, administration of neutralizing antibodies against TGF-beta significantly attenuated the disease in PAI-1 -/- mice. This suggests that the poor outcome of GN in PAI-1 -/- mice is consecutive to an uncontrolled activation of TGF-beta and confers PAI-1 with a new, immunomodulatory role.

Resume Propos. – La drepanocytose heterozygote est le plus souvent asymptomatique mais peut se manifester uniquement par une atteinte renale dominee par l’hematurie macroscopique. Methodes. – Nous rapportons dix cas de drepanocytose heterozygote reveles par une hematurie macroscopique et etudions les autres manifestations de la nephropathie. Resultats. – Six hommes et quatre femmes, de la population noire, âges de 17 a 53 ans, presentent une hematurie macroscopique, recidivante, persistante parfois jusqu’a deux ans, associee a des caillots dans cinq cas et des douleurs lombaires dans quatre cas. Les examens morphologiques de l’appareil urinaire sont normaux. La concentration des urines est perturbee chez tous les patients alors que les fonctions de dilution, tubulaire proximale et distale sont normales. Le repos et l’apport de boissons alcalines permettent une disparition de l’hematurie chez trois patients. La prescription d’acide epsilon-aminocaproique permet une disparition de l’hematurie chez trois patients mais laissent persister une hematurie microscopique chez trois autres. Le dernier patient est traite par l’apport oral d’uree qui laisse persister une hematurie microscopique. Conclusion. – L’association de facteurs chimiques et physiques dans la medullaire renale de la drepanocytose heterozygote est responsable d’hematurie macroscopique et de perturbations de la concentration des urines. Le diagnostic de l’hematurie macroscopique reste un diagnostic d’exclusion d’un autre element lesionnel de l’appareil urinaire. Le tableau clinique est le plus souvent benin. L’association de repos et de boissons alcalines permet souvent de faire disparaitre l’hematurie. En cas d’echec, le recours a des agents antifibrinolytiques comme l’aprotinine, l’uree par voie orale ou les gestes urologiques sont parfois necessaires.

Background. Chronic allograft nephropathy is the main cause of long-term kidney graft loss. The plasminogen activator inhibitor type 1 (PAI-1) is a potential fibrogenic molecule whose secretion is regulated by several metabolic, inflammatory, and genetic factors. We aimed to determine whether PAI-1 secretion in renal transplant patients is correlated with the decline in renal function after transplantation. Methods. Renal transplant patients (145 male/71 female) were included in the study 1-27 years after transplantation (median of follow-up: 7.35 years). At inclusion, routine clinical and biological data were collected, the 4G/5G polymorphism of the recipient PAI-1 gene was determined, and the PAI-1 plasma level was measured. Results. The mean rate of decline in renal function was -4.26±0.30 ml/min/year. By multiple linear regression analysis, the rate of decline in renal function was significantly correlated with proteinuria (P=0.0176), occurrence of late acute rejection episodes (P=0.0001), and PAI-1 plasma level (P=0.0051). In addition, PAI-1 plasma level was also significantly correlated with body mass index (P=0.038), insulin (P

A frequent complication in patients with kidney diseases,chronic anaemia is commonly treated with erythropoietin-stimulating agents (ESA). At present, the optimal target forhaemoglobin (Hb) concentration is, however, unknown.The purpose of this communication is to plead for a lessaggressive correction of nephrogenic anaemia, fully justi-fied by the adaptive mechanisms that patients on dialysisare prompt to set off in order to increase their tolerance toanaemia. First, their delivery of oxygen from Hb is oppor-tunely facilitated. Second, beyond a certain threshold, ris-ing Hb concentration with ESA does not mean increasingtissue oxygenation. Although the physiological adaptationin patients with kidney failure has been known for decades,it has been constantly and startlingly ignored in the designof studies aiming at a full correction of anaemia and an‘irrational’ normalizationofHbwiththeuseofESA.Flawed in essence, these studies also demonstrate the dan-gerousness of a generic approach.Historically, the food and drug administration (FDA) ap-proved the prescription of recombinant erythropoietin(rhuEPO) in 1989 on the basis of a signal study published2 years earlier showing that rHuEPO could eliminate theneedfortransfusionsinpatientswithend-stagerenaldisease(ESRD), and thereby protect them from immunologicsensitization, infection and iron overload [1]. Twenty yearslater, on 16 February 2010, the same FDA announced thatESA should actually be prescribed under a‘risk manage-ment programme’, known as the Risk Evaluation and Miti-gation Strategy: data collected in longitudinal clinicalstudies had indeed repeatedly shown that in patients withrenal disease or with solid tumours, complete correction ofanaemiawith ESA had increased the risk of death, nonfatalmyocardial infarction [2–4], fatal or nonfatal stroke andblood clots [4]. In retrospect, thus, excessive normalizationofHblevelswithESAmayhaveimprovedthequalityoflifeofpatientswithESRD[5,6]butattheexpenseofadecreasein their ‘quantity’ of life [3]. The reasons to avoid bloodtransfusion still prevail, though, and a low Hb will increasethe risk for cardiovascular events in these patients [7], aswell. Since experimental findings have strongly suggestedthat the side effects of ESA are essentially related to a risein haematocrit and not to some off-target properties of thedrugs [8], it is now time to revise our target downwards [9].Themajorfunctionofthecentralcirculationistotransportoxygen from the lungs to the peripheral tissues at a rate thatsatisfies overall oxygen consumption. There is no storagesystem for oxygen (O

Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increases in suPAR concentration result in FSGS-like glomerular lesions and proteinuria. However, whether overexpression of suPAR, per se, contributes to the pathogenesis of FSGS in humans remains controversial. We conducted an independent set of animal experiments in which two different and well characterized forms of recombinant suPAR produced by eukaryotic cells were administered over the short or long term to wild-type (WT) mice. In accordance with the previous study, the delivered suPARs are deposited in the glomeruli. However, such deposition of either form of suPAR in the kidney did not result in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria.

BACKGROUND Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis. METHODS Using the technique of Peten et al., we microdissected the glomeruli of 23 kidney transplanted patients admitted in our department from 1993 to 1997, and we followed-up these patients for up to 5 years, with sometimes iterative renal biopsies. With this technique, we also microdissected the glomeruli of three patients who have had a nephrectomy for cancer (control patients). We investigated mRNA expression of the PAI-1, the thrombin receptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a housekeeping gene (cyclophilin) by reverse transcription-polymerase chain reaction. The results were correlated with the renal function and the histological findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies). RESULTS A significant up-regulation of PAI-1 and alpha2 IV collagen mRNA was observed in acute rejection (P

Objective: To determine the epidemiological trends, spectrum of etiologies, morbidity and mortality of acute renal failure (ARF) in patients over 80 years old.¶Design: Historical cohort analysis.¶Setting: Intensive care unit (ICU) of nephrology, Tenon Hospital, Paris.¶Patients and participants: The criteria of inclusion was ARF, defined on the basis of a creatinine value over 120 μmol/l, in patients over 80 years of age admitted between October 1971 and September 1996. When moderate chronic nephropathy was pre-existing, ARF was defined by the increase of at least 50 % over the basal creatininemia.¶Measurements and results: Three hundred and eighty-one patients over 80 years of age were included. The etiology and mechanism of ARF are detailed. 29 % of the patients received dialysis. Global mortality at the hospital was 40 %. Factors significantly associated with a poor prognosis are identified. Mean survival after hospitalization was 19 months.¶Conclusion: The frequency of admission to ICUs for ARF in patients older than 80 years seems to be on the increase. Mortality is less severe than expected. These patients could benefit from the renal replacement therapy of modern intensive care medicine.

Summary Introduction Wernicke encephalopathy – most often observed in alcoholic patients – is due to severe thiamine deficiency. Case We report here the case of a 30-year-old woman who presented with hyperemesis and vomiting during the first trimester of pregnancy ( hyperemesis gravidarum ). Hyperemesis can lead to severe, symptomatic thiamine deficiency and to severe dehydration with prerenal azotemia. Discussion Wernicke encephalopathy is a rare complication of hyperemesis gravidarum. It should be diagnosed as early as possible to prevent long-term complications.

Resume Introduction La maladie de McArdle est une glycogenose musculaire de transmission autosomique recessive liee a un deficit en phosphorylase musculaire et caracterisee par des crampes a l'effort associees a une myoglobinurie. Fait clinique Nous rapportons une observation de rhabdomyolyse massive avec insuffisance renale aigue revelant une maladie de McArdle chez une patiente de 20 ans. Discussion L'atteinte musculaire est constante dans la maladie de McArdle, mais la survenue d'une rhabdomyolyse massive avec insuffisance renale aigue est un mode de revelation plus rare. Les mecanismes de l'atteinte renale ainsi que leurs consequences therapeutiques sont discutes.

Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line. The cells were exposed for 24 hours to preeclamptic or normal pregnancy plasma and their transcriptome was analyzed using Agilent microarrays. A total of 116 genes were found differentially expressed: 71 were up-regulated and 45 were down-regulated. In silico analysis revealed significant consistency and identified four functional categories of genes: mitosis and cell cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic reticulum stress effectors. Moreover, several genes involved in vasoregulation and endothelial homeostasis showed modified expression, including EDN1, APLN, NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a significant overrepresentation of genes containing activation protein-1 regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a repressor of activation protein-1. The role of JDP2 in the regulation of a subset of genes in the human umbilical vein endothelial cells was confirmed by siRNA inhibition. We characterized transcriptional changes induced by preeclamptic plasma on human umbilical vein endothelial cells, and identified, for the first time to our knowledge, JDP2 as a regulator of a subset of genes modified by preeclamptic plasma.

Alors que la physiopathologie du syndrome maternel de préeclampsie est beaucoup mieux comprise,celle de son versant placentaire, qui est le primummovens du syndrome, reste mystérieuse. Les outilsmodernes et spécifiques de mesure des stéroïdescomme la spectrométrie de masse après chromatographie gazeuse, ont cependant permis de détecterune diminution de la synthèse de l’œstradiol dansle sang des femmes accouchant dans un contextede préeclampsie. Ce défaut semble consécutif à undéfaut d’aromatisation des androgènes fœtaux etmaternels par le placenta. Ici, nous faisons l’hypothèse que ce défaut est précoce et joue un rôle causal dans les anomalies de la pseudovasculogénèseplacentaire qui caractérisent mais aussi induisent lapréeclampsie.

Levofloxacin , the l-isomer of ofloxacin has become one of the cornerstones of antibiotic therapy of pyelonephritis since its introduction in the 1990s, thanks to its exceptional pharmacokinetic (PK) and pharmacodynamic (PD) profile, broad-spectrum antibacterial action and satisfactory tolerance. However, the emergence of widespread fluoroquinolone resistance over the past decade, has prompted to re-examine its place in the treatment of urinary tract infection.This review covers the medical literature in any language through December 2012, on 'levofloxacin'. To identify relevant articles, the search terms 'pyelonephritis', 'urinary tract infections', 'levofloxacin', 'levaquin' and 'ofloxacin' were obtained through PubMed, MEDLINE and Clinicaltrials.gov queries. The authors focus on clinical trials, articles related to the PK and PD properties of levofloxacin as well as recent development in the mechanisms and prevalence of levofloxacin resistance. Major points stemming from international guidelines are also reviewed.Levofloxacin has achieved satisfactory bacterial eradication rates and clinical success across all available trials, similar to the antibiotic comparator. High-dose (750 mg) orally administrated levofloxacin over a short 5-day course is a reasonable option for patients eligible for outpatient management. Levofloxacin is no longer a suitable option for first-line empirical treatment of pyelonephritis in areas where resistance rates are high (10%) when pyelonephritis is hospital-acquired. Efforts to promote fluoroquinolone-sparing agents should be encouraged and its prescription should be performed in compliance with antimicrobial guidelines.

Summary In this ancillary study of the CONCEPT trial, we studied the role of CsA withdrawal at 3 months (3M) post-transplant on the intensity of epithelial phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12M surveillance biopsy. Although conversion from CsA to sirolimus (SRL) at 3M was reported to have improved mean graft function at 12M, it did not reduce the score of EPC (1.73 ± 1.15 in the SRL group vs. 1.87 ± 1 in the CsA group, P = 0.61). Acute rejection, which had occurred twice more frequently in SRL-converted patients included here, was associated with 12M EPC. Interestingly, we observed that the patients durably exposed to CsA and who developed 12M EPC had a significant progression of blood pulse pressure (pp) from 1 to 6M post-transplantation (Δpp = +12.3 mmHg, P = 0.0035). Pulse pressure at 4, 6, and 9M and pp progression from 1 to 6M were significantly associated with the development of EPC at 12M in renal grafts. Logistic regression analysis revealed that a high 6M pp (≥60 mmHg) was an independent risk factor for 12M EPC with an odds ratio of 2.25 per additional 10 mmHg pp (95%CI: 1.14–4.4, P = 0.02) after adjustment with recipient's and donor's age, acute rejection incidence and immunosuppressive regimen. A post hoc analysis of the data collected in the whole population CONCEPT study revealed that pp was significantly higher at 6 months in patients maintained on CsA and that at this time point pp correlated negatively with GFR at 1 year.

Renal transplantation is the best option for patients with end-stage renal disease (ESRD), but its half-life is limited to a decade. Clinical and histological markers measurable within the first year of transplantation can be used to predict its outcome. These markers are important for selecting kidneys for transplantation, for identifying the main causes of late allograft loss, for therapeutic decisions and as surrogate markers in therapeutic trials. ‘Basal state’ markers, such as age, glomerular filtration rate and fibrotic lesions, are highly predictive of allograft loss, showing that early and stable pathological mechanisms contribute considerably to this loss. On the other hand, some more dynamic predictors such as treatment, recurrence of the initial disease, inflammation and epithelial phenotypic changes offer clinicians and researchers opportunities to influence the fate of allografts.

Introduction Parmi les facteurs anti-angiogeniques produits par le placenta, sFlt-1 joue un role majeur dans la physiopathologie du syndrome maternel de pre-eclampsie. Son elevation est detectable dans le sang maternel plusieurs semaines avant les signes cliniques. L’etude MOMA (MOrbiMortality Amelioration in preeclamptic primiparas) a ete concue pour determiner si la prediction de la pre-eclampsie grâce au dosage de sFlt1 au sixieme mois de grossesse permettrait de diminuer la morbi-mortalite maternelle et fœtale. Patients et methodes MOMA est une etude interventionnelle prospective et randomisee ayant inclus dans le Centre d’obstetrique de Tenon des patientes adultes primipares, ayant accepte le dosage de sFlt-1 entre 24 et 29 semaines d’amenorrhee (SA), et un Doppler aux arteres uterines a 22 SA ± 10 jours. Le risque de pre-eclampsie etait d’abord stratifie sur la base du Doppler, puis calcule sur la base de la concentration de sFlt-1 (> 957 ng/mL), et communique a l’obstetricien dans un cas sur 2. En cas de risque juge eleve de pre-eclampsie (sFlt-1 eleve), les patientes etaient soumises a une surveillance accrue. Dans le groupe temoin, le risque etait mesure mais non communique. Le critere de jugement principal etait composite, associant differents facteurs de morbidite maternelle et fœtale. Resultats Au total, 939 femmes ont ete incluses, parmi lesquelles 466 ont constitue le groupe « sFlt-1 connu », et 473 le groupe « sFlt-1 masque ». L’incidence de la pre-eclampsie a ete de 7,3 % dans le groupe connu, 4,9 % dans le groupe masque. Le score de morbidite a ete identique dans les deux groupes, suggerant que le suivi rapproche des patientes a risque ne change pas le pronostic du syndrome. Le seuil choisi de la concentration de sFlt-1 a ete, a posteriori, bas. Mais sFlt-1 a une valeur pronostique : le score etait le plus eleve dans le quartile le plus eleve des concentrations. Discussion Si la concentration de sFlt-1 dans le sang maternel, entre 24 et 29 SA, est associee a la morbidite du syndrome de pre-eclampsie, le suivi rapproche des patientes a risque (meme si le risque a ici ete surestime) ne semble pas diminuer la morbidite, ce qui est logique en l’absence de traitement specifique disponible. Conclusion La mesure de la concentration de sFlt-1 dans le sang maternel entre 24 et 29 SA ne permet pas de diminuer la morbidite de la pre-eclampsie.

Introduction Une insuffisance renale aigue resolutive est desormais un facteur de risque reconnu d’insuffisance renale chronique. L’objectif de ce travail experimental etait d’analyser le comportement de l’epithelium tubulaire proximal apres une ischemie reperfusion et sa reponse en cas de deuxieme agression. Materiels et methodes Des souris C57Bl/6 adultes ont ete soumises a une nephrectomie et a une ischemie reperfusion controlaterale par le clampage du pedicule renal pendant 20 minutes (un groupe controle subissait seulement une nephrectomie, et un abord fantome du pedicule renal controlateral). Un mois plus tard, une perfusion continue pendant 4 semaines d’angiotensine 2 a ete administree par minipompes sous-cutanees pour induire une hypertension arterielle. Ont ete analyses : les parametres de la fonction renale, la fibrose renale et le transcriptome non biaise de l’epithelium tubulaire proximal isole ex vivo aux differents temps experimentaux (RNAseq). Resultats Quatre semaines apres l’ischemie reperfusion, l’insuffisance renale aigue etait pleinement resolutive, aux plans biologique et histologique, et la coloration par le rouge sirius ne montrait pas de fibrose. Comparativement aux souris ayant subi une chirurgie fantome, les souris ayant un antecedent d’insuffisance renale aigue resolutive ont developpe une fibrose interstitielle significativement plus marquee. L’analyse du transcriptome de l’epithelium tubulaire proximal montrait, au sacrifice, une augmentation significative des transcrits de la voie metabolique de la β-oxydation des acides gras. Par immunohistochimie, les cellules du cortex encore differenciees (exprimant la megaline) etaient, en effet, le lieu d’une surexpression de ces enzymes. Discussion Un antecedent d’insuffisance renale aigue par necrose tubulaire ischemique sensibilise le parenchyme renal a une fibrogenese acceleree en cas de deuxieme hit (ici, une hypertension arterielle). L’effondrement de la voie de la β-oxydation des acides gras, un mecanisme de fibrogenese renale, est probablement le fait des tubes atrophiques : les tubes encore differencies sont au contraire hyperactifs. Conclusion Notre travail modelise et eclaire l’acceleration de la fibrogenese renale apres une agression ischemique pourtant resolutive.

Introduction La maladie des anticorps anti-membrane basale glomerulaire (syndrome de Goodpasture) est une maladie auto-immune rare, causee par des anticorps anti-membrane basale glomerulaire. Elle est caracterisee par un syndrome pneumo-renal associant une glomerulonephrite rapidement progressive avec proliferation extra-capillaire et une hemorragie intra-alveolaire. L’atteinte renale est souvent brutale, severe, et greve le pronostic d’une lourde morbimortalite. Nous disposons de peu d’informations quant a la prevalence de l’atteinte pulmonaire et au pronostic renal compte-tenu du faible nombre de patients atteints. Patients et methodes Nous avons analyse de facon retrospective les caracteristiques cliniques et radiologiques, les modalites de traitement et l’evolution de 50 cas de maladie des anticorps anti-membrane basale glomerulaire. Resultats Dans notre population, le sexe ratio H/F etait de 1,2. Les patients etaient âges de 46,3 ans en moyenne, 39 % presentaient une intoxication tabagique chronique. Le mode de revelation etait le plus souvent brutal et associe a une alteration de l’etat general. Dans deux-tiers des cas, les patients ont ete pris en charge en nephrologie, et 39 % des patients ont necessite un sejour en reanimation medicale. Quatre-vingt-dix pour cent des patients ont presente une insuffisance renale aigue, le plus souvent severe avec 85 % d’epuration extrarenale d’emblee. Trente-huit pour cent des patients ont presente des manifestations respiratoires avec toux seche et hemoptysie. Un seul patient a presente une atteinte respiratoire severe isolee et a beneficie d’une transplantation bipulmonaire. Des anticorps anti-membrane basale glomerulaire ont ete mis en evidence par technique Elisa ou immunofluorescence dans 90 % des cas et 88 % des patients ont beneficie d’une ponction biopsie-renale qui a confirme la maladie sur le plan histologique. Concernant la prise en charge therapeutique, 92 % des patients ont beneficie d’echanges plasmatiques a raison de 12 seances au total en moyenne, ainsi qu’une corticotherapie systemique par bolus puis relais per os 1 mg/kg dans 84 % des cas. Un traitement par cyclophosphamide a ete initie dans 82 % des cas, le plus souvent par voie intraveineuse. Seuls 7 % des patients ont beneficie d’un traitement par rituximab. Un tiers des patients a beneficie d’une transplantation renale et aucune recidive apres transplantation n’a ete mise en evidence. La duree moyenne de suivi etait de 37 mois. En fin de suivi, 46 % des patients etaient toujours dialyses et 4 % sont decedes. Conclusion La maladie des anticorps anti-membrane basale glomerulaire est une vascularite rare dont le pronostic est severe. Le rituximab semble un traitement d’induction prometteur.

Silicone ganulomas usually arise from the rupture of silicone implants. Until the 1980s, however, underground care providers used to inject liquid and unapproved silicone directly into human tissues, in the absence of a containing capsule. We report here the case of a man who ultimately developed end-stage renal disease (ESRD) because of a chronic glomerulosclerosis that was attributed to a glomerular AA amyloidosis diagnosed 28 years after a buttock injection of liquid silicone. To our knowledge, this is the first case of a silicone-induced AA amyloidosis irreversibly affecting the kidneys, and leading to ESRD. An interleukin 1 receptor antagonist was started to prevent the extension of amyloidosis, but to no avail as far as the kidneys are concerned. We want to draw the attention of health professionals about the risk of developing AA amyloidosis secondary to a long-lasting inflammation induced by silicone leakage, after a long latency period.

Renal epithelial cells arise during embryogenesis by mesenchymal to epithelial transition (MET). In the context of renal diseases, these cells can switch back to a mesenchymal phenotype, in a process thus reminiscent of an epithelial-to-mesenchymal transition (EMT) in which we referred to as "Epithelial Phenotypic Changes" (EPC). The pathophysiological consequence of EPC is controversial: in particular, to what extent EPC contribute to the pool of disease-associated renal fibroblasts is very uncertain. However, there is strong evidence that EPC correlate with a poor renal outcome. EPC indeed reflect an exposure to a profibrotic environment, at an early and potentially reversible stage. Detecting EPC has potential therapeutic implications for patients prone to renal fibrosis, both as a marker of efficacy or more directly as a target. In opposition to the EMT occurring during embryogenesis, EMT in fibrosis as well as in cancer is an anarchic cellular process actually developing at the expense of the whole organ(ism).

Hemolytic and uremic syndrome (HUS) is the most feared complication of infections with enterohemorrhagic Escherichia coli. During summer 2011, Europe was the scene of a large outbreak of shiga-toxin producing E. coli gastroenteritis, occasioning more than 800 cases of HUS, highlighting this public health problem. Last years, many advances have occurred, on the physiopathology, microbiology or therapeutics. We review here these different aspects, from molecular identification of the German bacteria, to the use of targeted therapies as eculizumab in severe forms, or even the major role of complement activation in the physiopathology of HUS.

BACKGROUND A widely used immunosuppressant, cyclosporine A (CsA), conveys long-term nephrotoxicity in some patients. However, no specific marker is presently available. In both native and transplanted human kidneys, epithelial phenotypic changes (EPCs) suggestive of epithelial to mesenchymal transition (EMT) are expressed in various diseases and are prognostic with respect to progression of interstitial fibrosis. We hypothesized that CsA is able to trigger these EPCs in tubular cells in vivo. METHODS We studied the kinetics of the EMT markers β-catenin, snail, vimentin, collagen III, and HSP47 at the messenger RNA and protein levels in the kidneys from rats injected with 15 mg/kg/day of CsA or its vehicle. We investigated several therapeutic strategies available to block EMT in this model. RESULTS By 2 weeks, CsA had induced histological changes (tubular dilatation and vacuoles) and overexpression of EMT-related genes. This up-regulation of the EMT program was associated with tubular, not interstitial, overexpression of mesenchymal markers. Angiotensin II and endothelin receptor antagonists failed to prevent this CsA-induced EMT. Interestingly, CsA withdrawal led to the gradual regression of histological lesions and EMT, demonstrating that it not only prevents progression but also allows healing of renal injury. CONCLUSION Our study suggests that detecting EPC could help to identify ongoing renal CsA-induced toxicity at an early and reversible stage.

Maintenance immunosuppression with cyclosporine A (CsA) can cause nephrotoxicity in renal transplant recipients. Identifying patients at increased risk for CsA nephrotoxicity may allow interventions to prolong graft survival. Here, we studied the effect of early CsA withdrawal or maintenance among 96 kidney recipients at risk for interstitial fibrosis and tubular atrophy (IF/TA) on the basis of tubular expression of vimentin and β-catenin in a protocol biopsy performed 3 months after transplant. In this retrospective analysis of biopsies collected during a randomized trial of early withdrawal of CsA or mycophenolate mofetil, the semiquantitative score of early phenotypic changes suggestive of epithelial-to-mesenchymal transition (EMT) progressed with time among those maintained on a CsA-containing regimen. EMT-positive grafts displayed a significantly higher IF/TA score and greater progression of the IF/TA score at 12 months (P = 0.001 and 0.008, respectively). EMT-positive grafts exposed to CsA also had a greater decrease in estimated GFR compared with EMT-negative grafts exposed to CsA and EMT-positive grafts withdrawn from CsA exposure. Multivariable analysis revealed that the presence of EMT was an independent risk factor for a 10% decline in graft function up to 4 years posttransplant (odds ratio 4.49; 95% confidence interval 1.02 to 19.9). Collectively, these data demonstrate that changes consistent with EMT are strong prognostic biomarkers in renal transplant recipients exposed to CsA.

International audience; Over the past two decades, the concept of the epithelial to mesenchymal transition (EMT) has been imported from embryology and oncology to fibrosis, particularly in the kidney. This interest in EMT in the context of renal fibrosis stems from observations of epithelial cells undergoing phenotypic changes reminiscent of fibroblasts. Whether EMT is actually a source of interstitial fibroblasts has been the subject of heated debate, and this controversy has caused physicians to neglect the value of EMT as a biomarker in renal fibrosis. In this review, we describe the evolution of the techniques used to detect EMT during fibrosing renal diseases, and what information they provide in the diagnosis of various renal diseases. Highlighting the great heterogeneity of these techniques and the need to standardize them, we warn against some misleading uses of EMT markers. We suggest using the association of vimentin and β-catenin for the diagnosis of EMT in renal pathology because it is both sensitive and prognostic, thus satisfying the properties required for a screening test. Finally, we discuss the potential interests to diagnose EMT for the comprehension of renal fibrosis and for clinical practice.

Introduction Il a ete recemment suggere qu’un episode d’insuffisance renale aigue triple le risque d’insuffisance renale terminale dans les dix ans qui suivent [1] . De 15 a 45 % des patients developpent une acute kidney injury apres une chirurgie cardiaque (hausse de creatininemie de 0,3 mg/dL en moins de 48 h ou de 50 % en 7 jours) [1] , [2] . Le pronostic renal de ces patients reste meconnu. L’objectif de ce travail etait de suivre la fonction renale des patients indemnes de toute insuffisance renale avant la chirurgie, et ayant developpe une AKI transitoire. Patients et methodes Une etude retrospective a ete conduite sur le CHU de Caen. Celle-ci a inclus l’ensemble des patients ayant beneficie d’une chirurgie cardiaque entre septembre 2010 et decembre 2013. Les patients presentant une insuffisance renale chronique avant la chirurgie ont ete exclus. Resultats Parmi les 2015 patients ayant beneficie d’une chirurgie cardiaque, 1694 (84 %) avaient un DFG preoperatoire estimable ; 447 patients ont ete exclus en raison d’une insuffisance renale chronique preexistante. Sur les 1247 patients restants, 432 (35 %) ont developpe une AKI en postoperatoire, dont la majorite (295 patients, 68 %) a recupere en 30 jours une fonction renale equivalente (± 5 %) a celle estimee en preoperatoire. Au terme du suivi, 21 patients du groupe AKI ont developpe une insuffisance renale chronique, contre 1 patient seulement dans le groupe sans AKI (p Discussion et conclusion L’AKI est frequente apres une chirurgie cardiaque. Elle ne suscite generalement pas une attention particuliere pour trois raisons : elle est par definition d’intensite moderee, il n’y a aucun traitement specifique, et enfin son pronostic renal immediat est relativement bon. Notre etude montre pourtant que, dans ce contexte, une AKI meme reversible est associee a un risque accru de developper une insuffisance renale chronique a moyen terme. Ces resultats consolident l’idee recente qu’il existe comme un effet memoire d’un episode d’insuffisance renale aigue [1] . Ils incitent a proposer un suivi nephrologique chez ces patients.

Every year in the United States, 5000 renal transplant recipients start or restart dialysis because of the unusual propensity of these allografts to develop interstitial fibrosis and tubular atrophy (IF/TA). Although IF/TA often follows one or more identifiable events, our capacity to specifically treat, prevent, or even detect IF/TA at an early stage is poor. These limitations are largely related to our lack of adequate tools to assess graft failure over time. Data accumulated over the past 5 years have demonstrated that tubular epithelial cells may react to certain fibrogenic stimuli to engage in the process of epithelial-to-mesenchymal transition (EMT). In this review, we highlight the current view of EMT with a focus on both its role in the context of renal transplantation and the potential for utilizing markers of EMT to identify patients undergoing early IF/TA.

Late loss of renal grafts is primarily due to progressive sclerosis, involving both immune and non immune processes. Activation of interstitial fibroblasts responsible for graft fibrosis is known to involve proliferation and activation of resident fibroblasts, recruitment of bone marrow-derived stem cells, and epithelial-mesenchymal transition, a more recently identifled mechanism. In this latter process, tubular epithelial cells lose their epithelial phenotype, acquire mesenchymal markers and properties, and participate in the fibrotic process. Whether or not these cells move into the interstitium is controversial. By using immunohistochemistry with specific antibodies against vimentin, beta cadherin, beta catenin and other fibroblastic markers, we found that tubular epithelial cells in kidney grafts can exhibit phenotypic markers of epithelial-mesenchymal transition as early as 3 months after transplantation, before the onset of fibrosis. These changes are associated with prolonged cold ischemia and clinical or subclinical acute rejection. In addition, changes observed at 3 months seem to be predictive of both the fibrosis score at 12 months and, interestingly, the progression of fibrosis between 3 months and 12 months. Finally, renal function at 2 years was significantly poorer in patients exhibiting epithelial changes at 3 months. These results suggest that the epithelial-mesenchymal transition plays a role in the progressive fibrosis of kidney grafts, and that its early inhibition could prevent the gradual decline in renal function and late graft loss.

The transcription factor Snail is an important repressor of E-cadherin gene expression. It plays a key role in the induction of epithelial-mesenchymal transition, an essential process important not only in embryonic development and tumor progression but also in organ fibrogenesis. We studied the expression of Snail by immunohistochemistry, along with several epithelial phenotypic changes suggestive of epithelial-mesenchymal transition, in 14 patients with multiple myeloma cast nephropathy. This nephropathy is characterized by a rapid progression toward fibrosis. As controls, we used normal kidneys and kidneys from patients displaying an idiopathic nephrotic syndrome, a syndrome unassociated with renal fibrosis. We discovered that, in all patients with multiple myeloma nephropathy, a drastic accumulation of Snail is seen in the nuclei from tubular epithelial cells showing epithelial phenotypic changes. In contrast, normal and idiopathic nephrotic syndrome kidneys did not exhibit either of these markers. Snail, a major player in the process of epithelial-to-mesenchymal transition, is highly expressed by tubular epithelial cells during multiple myeloma nephropathy. It is, therefore, a potential target to prevent multiple myeloma kidneys from fibrosing. Intranuclear accumulation of Snail is a characteristic in phenotypically altered tubular cells from multiple myeloma kidneys. The epithelial-mesenchymal transition pathway could, therefore, be involved in the rapid renal fibrogenesis observed in this setting.

The formation of new vessels (aka neo-angiogenesis) is critical for tumoral progression. Although anti-angiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway are employed since less than ten years in human patients, they are now a key player in the treatment of advanced stage malignant tumors. An endothelial syndrome, characterized by hypertension and glomerular proteinuria, complicates this treatment in roughly 25% of patients. From a pathophysiological perspective, this may be considered as a preeclampsia-like syndrome. While the most severe forms require the interruption of the regimen, this syndrome is usually mild or moderate, and should be treated by the addition of an anti-hypertensive drug.

Preeclampsia (PE) is one of the most common diseases worldwide, complicating ~ 5% of all pregnancies. Although no major progress has been achieved in the treatment of PE, our ability to identify women at high-risk has increased considerably during the past decade. Thus, the soluble form of the type-1 receptor of vascular endothelial growth factor (sFlt1) and of endoglin (sEng), an endothelial receptor for transforming growth factor beta, have been shown to increase dramatically in the maternal blood of the women affected some weeks before the onset of clinical symptoms. A relative concomitant fall in VEGF and placental growth factor (PlGF) has also been reported. In 2010, they are the most promising biomarkers for PE. The extent to which they are involved in the pathophysiology of the maternal syndrome and of the primary placental disorder responsible for PE is being actively investigated. In parallel, defective placental steroidogenesis, as well as the loss of tolerance towards the angiotensin-2 receptor have also been found to be critically involved in mouse models of PE. Although there is not much data to support their role in human PE, these two biological pathways are a potential future source of both new biomarkers, and new therapeutic strategies. The aim of this review is to compare the likely value of these molecules at the bedside, and to discuss their implication in the pathophysiology of what used to be known as “the disease of theories”.

Hemolytic uremic syndrome (HUS) is related to a renal thrombotic microangiopathy, inducing hypertension and acute renal failure (ARF). Its pathogenesis involves an activation/lesion of microvascular endothelial cells, mainly in the renal vasculature, secondary to bacterial toxins, drugs, or autoantibodies. An overactivation of the complement alternate pathway secondary to a heterozygote deficiency of regulatory proteins (factor H, factor I or MCP) or to an activating mutation of factor B or C3 can also result in HUS. Less frequently, renal microthrombi are due to an acquired or a constitutional deficiency in ADAMTS-13, the protease cleaving von Wilebrand factor. Hemolytic anemia with schistocytes, thrombocytopenia without evidence of disseminated intravascular coagulation, and renal failure are consistently found. In typical HUS, a prodromal diarrhea, with blood in the stools, is observed, related to pathogenic enterobacteria, most frequently E. Coli O157:H7. HUS may also occur in the post partum period, and is then related to a factor H or factor I deficiency. HUS may also occur after various treatments such as mitomycin C, gemcitabine, ciclosporin A, or tacrolimus, and as reported more recently bevacizumab, an anti VEGF antibody. Atypical HUS are not associated with diarrhea, may be sporadic or familial, and can be related to an overactivation of the complement alternate pathway. More recently, some of them have been related to a mutation of thrombomodulin, which also regulates the alternate pathway of complement. In adults, several HUS are encountered in the course of chronic nephropathies: nephroangiosclerosis, chronic glomerulonephritis, post irradiation nephropathy, scleroderma, disseminated lupus erythematosus, antiphospholipid syndrome. Overall the prognosis of HUS has improved, with a patient survival greater than 85% at 1 year. Chronic renal failure is observed as a sequella in 20 to 65% of the cases. Plasma infusions and plasma exchanges are effective in most of the cases to treat hemolysis and thrombocytopenia. Steroid therapy is debated, as well as immunosuppressive drugs, including rituximab, in autoimmune forms. A new monoclonal anti-C5 antibody is tested, and seems to be effective in atypical HUS with abnormal complement alternate pathway activation. If terminal renal failure occurs, renal transplantation can be performed but the risk of recurrence, which very low in post infectious forms of HUS, is about 70 to 80% in genetic forms of complement regulatory protein deficiency.

Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell-mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers.

In renal grafts, the progression of interstitial fibrosis and tubular atrophy (IF/TA) is exponential during the first months post-transplant. Consequently, roughly 40% of the cadaveric grafts will function less than ten years. There is, however, no specific strategy to halt fibrogenesis, i.e. the progression of fibrosis with time, in kidney recipients. Epithelial to mesenchymal transition (EMT) is a biological process used to disperse cells during embryogenesis. In the setting of injury, it is also a mechanism to escape cellular death. The last five years, several studies demonstrated that EMT does occur in tubular epithelial cells, which have been shown to loose the expression of epithelial markers, and acquire the expression of mesenchymal proteins, like vimentin. The aim of this review is triple: 1) discuss the connections between EMT and the context of transplantation; 2) explain how EMT markers may be useful in clinical practice, as promising surrogate markers for fibrogenesis; 3) discuss some therapeutic perspectives.

The pathogenesis of the HELLP (hemolysis, enzyme liver, low platelets) syndrome is unknown. Recently soluble endoglin (sEng) was identified as a cause of the appearance of schistocytes and liver pathology in an animal model of preeclampsia (PE).We explored the value of sEng in 82 women who delivered in a context of normal pregnancy (NP, n = 10), PE (n = 49), or HELLP (n = 23).sEng was elevated in pathological pregnancies (66.7 +/- 62 and 75.7 +/- 48 pg/mL in PE and HELLP, respectively, vs 5.29 +/- 1.25 in NP, P.001 for both comparisons) and was correlated with an increase in transaminases (r(2) = 0.17; P = .05), but it was not statistically different between PE and HELLP.Although recent literature findings demonstrated a role of sEng in the pathophysiology of HELLP syndrome in animal models, we found that, at the time of delivery, sEng was not specifically elevated in preeclamptic patients with HELLP.