Impact of first-wave COronaVIrus disease 2019 infection in patients on haemoDIALysis in Alsace: the observational COVIDIAL study.

BACKGROUND: There are only scarce data regarding the presentation, incidence, severity and outcomes of coronavirus disease 2019 (COVID-19) in patients undergoing long-term haemodialysis (HD). A prospective observational study was conducted in eight HD facilities in Alsace, France, to identify clinical characteristics of HD patients with COVID-19 and to assess the determinants of the risk of death. METHODS: All HD patients tested positive for COVID-19 from 5 March to 28 April 2020 were included. Collected data included patient characteristics, clinical features at diagnosis, laboratory data, treatments and outcomes. RESULTS: Among 1346 HD patients, 123 tested positive for COVID-19. Patients had a median age of 77 years (interquartile range 66-83), with a high number of comorbidities (3.2 ± 1.6 per patient). Symptoms were compatible in 63% of patients. Asthenia (77%), diarrhoea (34%) and anorexia (32%) were frequent at diagnosis. The delay between the onset of symptoms and diagnosis, death or complete recovery was 2 (0-5), 7 (4-11) and 32 (26.5-35) days, respectively. Treatment, including lopinavir/ritonavir, hydroxychloroquine and corticosteroids, was administered in 23% of patients. The median C-reactive protein (CRP) and lymphocyte count at diagnosis was 55 mg/L (IQR 25-106) and 690 Ly/µL (IQR 450-960), respectively. The case fatality rate was 24% and determinants associated with the risk of death were body temperature {hazard ratio [HR] 1.96 [95% confidence interval (CI) 1.11-3.44]; P = 0.02} and CRP at diagnosis [HR 1.01 (95% CI 1.005-1.017); P < 0.0001]. CONCLUSIONS: HD patients were found to be at high risk of developing COVID-19 and exhibited a high rate of mortality. While patients presented severe forms of the disease, they often displayed atypical symptoms, with the CRP level being highly associated with the risk of death.

Metabolic syndrome in haemodialysis patients: prevalence, determinants and association to cardiovascular outcomes.

BACKGROUND: In the general population, metabolic syndrome (MetS) is predictive of major adverse cardiovascular events (MACE). Waist circumference (WC), a component of the MetS criteria, is linked to visceral obesity, which in turn is associated with MACE. However, in haemodialysis (HD) patients, the association between MetS, WC and MACE is unclear. METHODS: In a cross-sectional study of 1000 HD patients, we evaluated the prevalence and characterised the clinical predictors of MetS. The relationship between MetS and its components, alone or in combination, and MACE (coronary diseases, peripheral arteriopathy, stroke or cardiac failure), was studied using receiver operating characteristics (ROC) curves and logistic regression. RESULTS: A total of 753 patients were included between October 2011 and April 2013. The prevalence of MetS was 68.5%. Waist circumference (> 88 cm in women, 102 cm in men) was the best predictor of MetS (sensitivity 80.2; specificity 82.3; AUC 0.80; p <  0.05). In multivariate analysis, MetS was associated with MACE (OR: 1.85; 95CI 1.24-2.75; p <  0.01), but not WC alone. There was a stronger association between the combination of abdominal obesity, hypertriglyceridaemia and low high-density lipoprotein cholesterol with MACE after exclusion of impaired fasting glucose and hypertension. CONCLUSIONS: MetS is frequent and significantly associated with MACE in our haemodialysis cohort and probably in other European dialysis populations as well. In HD patients, a new simplified definition could be proposed in keeping with the concept of the "hypertriglyceridaemic waist".

Pre-existing donor-specific antibodies are detrimental to kidney allograft only when persistent after transplantation.

Donor-specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty-seven patients (15.5%) had pre-existing DSA detected the day of transplantation. After 5 years, the pre-existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years (P = 0.009), a history of previous transplantation (P = 0.039), the presence of class II DSA (P = 0.009), an MFI of preformed DSA >3500 (P < 0.001), and the presence of two or more DSA (P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody-mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation.

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study.

BACKGROUND: Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation. METHODS: The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared. RESULTS: The mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03-6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status. CONCLUSIONS: KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

Kidney biopsy for the diagnosis and treatment of kidney diseases. Recommendations from the French speaking Society of Nephrology (SFNDT) and French National Authority for Health (HAS) 2022

Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.

La biopsie rénale (BR) est un outil diagnostique crucial dans le domaine des maladies rénales et est pratiquée en routine dans les services de néphrologie. Une précédente enquête menée par la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a révélé d'importantes disparités dans les pratiques cliniques, parfois en contradiction avec la littérature existante et les recommandations récemment publiées. En réponse, la SFNDT a souhaité promouvoir l'élaboration de recommandations de bonnes pratiques, sous l'égide de la Haute Autorité de santé (HAS), afin d'établir un cadre standardisé pour la réalisation des biopsies rénales en France.

External validation of the 2-year mortality prediction tool in hemodialysis patients developed using a Bayesian network.

Background: In recent years, a number of predictive models have appeared to predict the risk of medium-term mortality in hemodialysis patients, but only one, limited to patients aged over 70 years, has undergone sufficiently powerful external validation. Recently, using a national learning database and an innovative approach based on Bayesian networks and 14 carefully selected predictors, we have developed a clinical prediction tool to predict all-cause mortality at 2 years in all incident hemodialysis patients. In order to generalize the results of this tool and propose its use in routine clinical practice, we carried out an external validation using an independent external validation database. Methods: A regional, multicenter, observational, retrospective cohort study was conducted to externally validate the tool for predicting 2-year all-cause mortality in incident and prevalent hemodialysis patients. This study recruited a total of 142 incident and 697 prevalent adult hemodialysis patients followed up in one of the eight Association pour l'Utilisation du Rein Artificiel dans la région Lyonnaise (AURAL) Alsace dialysis centers. Results: In incident patients, the 2-year all-cause mortality prediction tool had an area under the receiver curve (AUC-ROC) of 0.73, an accuracy of 65%, a sensitivity of 71% and a specificity of 63%. In prevalent patients, the performance for the external validation were similar in terms of AUC-ROC, accuracy and specificity, but was lower in term of sensitivity. Conclusion: The tool for predicting all-cause mortality at 2 years, developed using a Bayesian network and 14 routinely available explanatory variables, obtained satisfactory external validation in incident patients, but sensitivity was insufficient in prevalent patients.

Impaired platelet P2Y12 inhibition by thienopyridines in chronic kidney disease: mechanisms, clinical relevance and pharmacological options.

Patients with chronic kidney disease (CKD) represent an increasing proportion of the population undergoing percutaneous coronary intervention (PCI) and up to 40% of the patients treated for acute coronary syndrome (ACS). Several studies and registries in the setting of ACS and elective PCI have reported a negative association between CKD and mortality, stent thrombosis, post-procedural ischaemic events and bleeding events. Pharmacological inhibition of the adenosine diphosphate receptor by thienopyridines or ticagrelor and disruption of the cyclooxygenase pathway by aspirin constitute the current standards of care to prevent thrombotic complications following stent-based PCI. In CKD patients, the avoidance of anti-platelet therapy may be driven by the lack of clinical trial data to support its efficacy, by errors or omissions, or by a reluctance to use this therapy in a population characterized by its enhanced bleeding risk. However, there is growing evidence to suggest that a severely decreased glomerular filtration rate per se, independent of the presence of diabetes mellitus, is an important determinant of high residual platelet reactivity under a clopidogrel maintenance dose. Recent reports have emphasized that the impact of impaired platelet inhibition by thienopyridines is of paramount importance in CKD patients, with an enhanced mortality rate in low-responder patients. Pharmacodynamic studies indicate the phosphodiesterase 3 inhibitor, cilostazol, the third generation thienopyridine prasugrel and the reversible P2Y12 antagonist ticagrelor to be potent strategies to overcome this biological resistance. In clinical practice, platelet function testing should be considered in CKD patients undergoing PCI, especially in those who experience thrombotic events despite dual therapy. Newer agents should be contemplated in patients who display higher residual platelet aggregability after standard treatment. Among these, the non-thienopyridine P2Y12 receptor antagonist ticagrelor, which does not require biotransformation, could be the drug of choice in CKD patients with ACS. In this population, ticagrelor has been found to reduce mortality and ischaemic events with an acceptable bleeding risk.

Identification of a leucine-zipper motif in pUL51 essential for HCMV replication and potential target for antiviral development.

Human cytomegalovirus (HCMV) can cause serious diseases in immunocompromised patients. Use of current antivirals is limited by their adverse effects and emergence of drug resistance mutations. Thus, new drugs are an urgent need. The terminase complex (pUL56-pUL89-pUL51) represents a target of choice for new antivirals development. pUL51 was shown to be crucial for the cleavage of concatemeric HCMV DNA and viral replication. Its C-terminal part plays a critical role for the terminase complex assembly. However, no interaction domain is clearly identified. Sequence comparison of herpesvirus homologs and protein modelling were performed on pUL51. Importance of a putative interaction domain is validated by the generation of recombinant viruses with specific alanine substitutions of amino acids implicated in the domain. We identified a Leucine-Zipper (LZ) domain involving the leucine residues L126-X6-L133-X6-L140-X6-L147 in C-terminal part of pUL51. These leucines are crucial for viral replication, suggesting the significance for pUL51 structure and function. A mimetic-peptide approach has been used and tested in antiviral assays to validate the interaction domain as a new therapeutic target. Cytotoxicity was evaluated by LDH release measurement. The peptide TAT-HK29, homologous to the pUL51-LZ domain, inhibits HCMV replication by 27% ± 9% at 1.25 µM concentration without cytotoxicity. Our results highlight the importance of a leucine zipper domain in the C-terminal part of pUL51 involving leucines L126, L133, L140 and L147. We also confirm the potential of mimetic peptides to inhibit HCMV replication and the importance to target interaction domains to develop antiviral agents.

Association of estimated GFR with platelet inhibition in patients treated with clopidogrel.

BACKGROUND: The reasons that decreased glomerular filtration rate (GFR) might alter the clinical efficacy of clopidogrel are poorly understood. STUDY DESIGN: In this study, we sought to evaluate whether decreased GFR alters platelet response to clopidogrel in patients receiving a maintenance dose of clopidogrel (75 mg/d for at least 8 days). SETTINGS & PARTICIPANTS: 126 consecutive patients categorized by estimated GFR: stages 1-2 (>60 mL/min/1.73 m(2); n = 29), stage 3a (45-59 mL/min/1.73 m(2); n = 21); stage 3b (30-44 mL/min/1.73 m(2); n = 26), stage 4 (15-29 mL/min/1.73 m(2); n = 14), and stage 5 (<15 mL/min/1.73 m(2); n = 36) were prospectively enrolled. PREDICTOR: Residual platelet reactivity, defined in the VASP (Vasodilator Stimulated Phosphoprotein) flow cytometry test as platelet reactivity index (PRI) ≥61% and in the VerifyNow turbidimetric-based assay as a value >235 PRU (adenosine diphosphate receptor reaction units) or percentage of platelet inhibition <15%. OUTCOMES: We examined factors associated with low response to clopidogrel using logistic regression. RESULTS: A significant relationship between estimated GFR, PRI, PRU, and percentage of inhibition was found. The prevalence of residual platelet reactivity was highest in patients with GFR stage 5. PRI ≥61% occurred in 52.8% of patients with stage 5 versus 30.8% of stage 3b and 24.1% of stages 1-2 (P = 0.1). PRU >235 was found in 63.6% of patients with stage 5 versus 36.8% of stage 3b and 17.2% of stages 1-2 (P = 0.005). Inhibition <15% affected 66.7% of patients with stage 5 versus 21.1% of stage 3b and 17.2% of stages 1-2 (P < 0.001). In the multivariable model, GFR stage 5 (adjusted prevalence ratio [PR], 3.10; 95% CI, 1.23-9.43; P = 0.02), and obesity (adjusted PR, 1.92; 95% CI, 1.34-2.23; P = 0.004) were the sole predictors of residual platelet reactivity. LIMITATIONS: Interference of hemodialysis with the pharmacokinetics of clopidogrel could not be excluded. CONCLUSION: GFR stage 5 is associated with substantial impairment of platelet inhibition independently of diabetes mellitus.

Evaluation of a predictive model of end-stage kidney disease in a French-based cohort.

BACKGROUND: The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case-control cohort and test the pertinence of the proposed thresholds. METHODS: A retrospective case-control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3-5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone. RESULTS: 314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48-0.79; and OR 0.72, 95% CI 0.59-0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02-1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60-0.72, p = 0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60-0.72, p = 0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64-0.76, p = 0.526). A 40% and 20% score thresholds were not superior to eGFR < 15 and 20 mL/min/1.73 m2, respectively. A 10% threshold was more specific than an eGFR < 30 mL/min/1.73 m2. CONCLUSION: KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.

Potential of Anti-CMV Immunoglobulin Cytotect CP® In Vitro and Ex Vivo in a First-Trimester Placenta Model.

BACKGROUND: Congenital CMV infection is the leading cause of neonatal neurological deficit. We herein studied in vitro and ex vivo the potential of the hyperimmune globulin Cytotect CP® (Biotest, Germany) for congenital infection prevention and treatment. METHODS: In vitro neutralization assays were conducted in fibroblasts and retinal epithelial cells on the CMV strains TB40/E and VHL/E to determine the 50% and 90% neutralizing doses (ND50 and ND90). The toxicity was assessed by measuring LDH release. Ex vivo assays were conducted in first-trimester villi explants with the TB40/E strain, namely, neutralization assays, the prevention of villi infection, and the inhibition of viral replication in infected villi. Viability was assessed by ß-HCG quantification in supernatants. RESULTS: The in vitro neutralization tests showed that Cytotect CP®® inhibits the development of infection foci (DN50: 0.011-0.014 U/mL for VHL/E and 0.032-0.033 U/mL for TB40E) without any toxicity. In the ex vivo neutralization assays, the DN50 were 0.011 U/mL on day 7 and 0.093 U/mL on day 14. For the prevention of villi infection, the EC50 was 0.024 U/mL on day 7. Cytotect-CP® did not inhibit viral growth in infected villi. No impact on villi viability was observed. CONCLUSIONS: These results sustained that Cytotect CP® has the potential to prevent CMV congenital infection.

First clinical description of letermovir resistance mutation in cytomegalovirus UL51 gene and potential impact on the terminase complex structure.

BACKGROUND: Letermovir (LMV) is a human cytomegalovirus (HCMV) terminase inhibitor indicated as prophylaxis for HCMV-positive stem-cell recipients. Its mechanism of action involves at least the viral terminase proteins pUL56, pUL89 and pUL51. Despite its efficiency, resistance mutations were characterized in vitro and in vivo, largely focused on pUL56. To date, mutations in pUL51 in clinical resistance remain to be demonstrated. METHODS: The pUL51 natural polymorphism was described by sequencing 54 LMV-naive strains and was compared to UL51 HCMV genes from 16 patients non-responding to LMV therapy (prophylaxis or curative). Recombinant viruses were built by «en-passant¼ mutagenesis to measure the impact of the new mutations on antiviral activity and viral growth. Structure prediction was performed by homology modeling. The pUL51 final-model was analyzed and aligned with the atomic coordinates of the monomeric HSV-1 terminase complex (PDB:6M5R). RESULTS: Among the 16 strains from treated-patients with LMV, 4 never described substitutions in pUL51 (D12E, 17del, A95V, V113L) were highlighted. These substitutions had no impact on viral fitness. Only UL51-A95V conferred 13.8-fold increased LMV resistance level by itself (IC50 = 29.246 ± 0.788). CONCLUSION: As an isolated mutation in pUL51 in a clinical isolate can lead to LMV resistance, genotyping for resistance should involve sequencing of the pUL51, pUL56 and pUL89 genes. With terminase modelling, we make the hypothesis that LMV could bind to domains were UL56-L257I and UL51-A95V mutations were localized.

Structures and Divergent Mechanisms in Capsid Maturation and Stabilization Following Genome Packaging of Human Cytomegalovirus and Herpesviruses.

Herpesviruses are the causative agents of several diseases. Infections are generally mild or asymptomatic in immunocompetent individuals. In contrast, herpesvirus infections continue to contribute to significant morbidity and mortality in immunocompromised patients. Few drugs are available for the treatment of human herpesvirus infections, mainly targeting the viral DNA polymerase. Moreover, no successful therapeutic options are available for the Epstein-Barr virus or human herpesvirus 8. Most licensed drugs share the same mechanism of action of targeting the viral polymerase and thus blocking DNA polymerization. Resistances to antiviral drugs have been observed for human cytomegalovirus, herpes simplex virus and varicella-zoster virus. A new terminase inhibitor, letermovir, recently proved effective against human cytomegalovirus. However, the letermovir has no significant activity against other herpesviruses. New antivirals targeting other replication steps, such as capsid maturation or DNA packaging, and inducing fewer adverse effects are therefore needed. Targeting capsid assembly or DNA packaging provides additional options for the development of new drugs. In this review, we summarize recent findings on capsid assembly and DNA packaging. We also described what is known about the structure and function of capsid and terminase proteins to identify novels targets for the development of new therapeutic options.

New Insights into Human Cytomegalovirus pUL52 Structure.

Human cytomegalovirus (HCMV) can cause serious diseases in immunocompromised patients. Current antiviral inhibitors all target the viral DNA polymerase. They have adverse effects, and prolonged treatment can select for drug resistance mutations. Thus, new drugs targeting other stages of replication are an urgent need. The terminase complex (pUL56-pUL89-pUL51) is highly specific, has no counterpart in the human organism, and thus represents a target of choice for new antivirals development. This complex is required for DNA processing and packaging. pUL52 was shown to be essential for the cleavage of concatemeric HCMV DNA and crucial for viral replication, but its functional domains are not yet identified. Polymorphism analysis was performed by sequencing UL52 from 61 HCMV naive strains and from 14 HCMV strains from patients treated with letermovir. Using sequence alignment and homology modeling, we identified conserved regions and potential functional motifs within the pUL52 sequence. Recombinant viruses were generated with specific serine or alanine substitutions in these putative patterns. Within conserved regions, we identified residues essential for viral replication probably involved in CXXC-like or zinc finger motifs. These results suggest that they are essential for pUL52 structure/function. Thus, these patterns represent potential targets for the development of new antivirals.

Kidney transplantation for active multiple myeloma or smoldering myeloma: a case-control study.

BACKGROUND: The increased survival of patients with multiple myeloma (MM) raises the question of kidney transplantation (KT) in patients with end-stage renal disease (ESRD). METHODS: We included 13 patients with MM or smoldering myeloma (SMM) and ESRD transplanted between 2007 and 2015, including 7 MM with cast nephropathy, 3 with MM-associated amyloid light chain amyloidosis or light chain deposition disease and 3 SMM and compared them with 65 control-matched kidney-transplanted patients. Nine of the MM patients with KT were also compared with 63 matched MM patients on haemodialysis. RESULTS: Pre-transplantation parameters were comparable, except for the duration of renal replacement therapy (57.8 versus 37.0 months; P = 0.029) in MM versus control patients, respectively. The median follow-up post-KT was 44.4 versus 36.4 months (P = 0.40). The median MM graft and patient survival were 80.1 and 117.2 months, respectively, and were not significantly different from control patients, although mortality tended to be higher in the 10 symptomatic MM patients (P = 0.059). MM patients had significantly more viral and fungal infections and immunosuppressive maintenance therapy modifications while they received lower induction therapy. Two MM patients relapsed and two SMM cases evolved to MM after KT. Three cast nephropathies occurred, two of them leading to ESRD. Moreover, survival of MM with KT increased relative to control haemodialysed patients (P = 0.002). CONCLUSIONS: Selected MM patients may benefit from KT but need careful surveillance in the case of KT complications and MM evolution.

[The terminase complex, a relevant target for the treatment of HCMV infection]. / Le complexe terminase, une cible de choix dans le traitement de l'infection à cytomégalovirus humain.

Human cytomegalovirus (HCMV) is an important ubiquitous opportunistic pathogen that belongs to the betaherpesviridae. Primary HCMV infection is generally asymptomatic in immunocompetent individuals. In contrast, HCMV infection causes serious disease in immunocompromised patients and is the leading cause of congenital viral infection. Although they are effective, the use of conventional molecules is limited by the emergence of resistance and by their toxicity. New antivirals targeting other replication steps and inducing fewer adverse effects are therefore needed. During HCMV replication, DNA packaging is performed by the terminase complex, which cleaves DNA to package the virus genome into the capsid. With no counterpart in mammalian cells, these terminase proteins are ideal targets for highly specific antivirals. A new terminase inhibitor, letermovir, recently proved effective against HCMV in phase III clinical trials. However, its mechanism of action is unclear and it has no significant activity against other herpesvirus or non-human CMV.

TITLE: Le complexe terminase, une cible de choix dans le traitement de l'infection à cytomégalovirus humain. ABSTRACT: Le cytomégalovirus humain (CMVH) est un pathogène opportuniste majeur en cas d'immunodépression et représente la principale cause d'infection congénitale d'origine virale. Bien qu'efficace, l'utilisation des molécules conventionnelles est limitée par leur toxicité et par l'émergence de résistance du virus, rendant nécessaire le développement de nouveaux traitements. Lors de la réplication du CMVH, l'encapsidation de l'ADN est réalisée par le complexe terminase qui clive l'ADN pour empaqueter le génome dans la capside. L'absence d'homologues dans les cellules des mammifères rend les protéines du complexe terminase des cibles idéales pour des antiviraux spécifiques. Une nouvelle molécule, le letermovir, cible une étape exclusivement virale en interagissant avec le complexe terminase. Son efficacité a été prouvée lors d'essais cliniques de phase III. Néanmoins, son mécanisme d'action n'est, à ce jour, pas élucidé et aucune activité n'est observée contre les autres herpèsvirus.

A confusional state associated with use of lanthanum carbonate in a dialysis patient: a case report.

A 75-year-old woman was admitted with febrile confusion and abdominal pain. She was taking medications that included lanthanum carbonate. Examination, biology, a cerebral scan, and a review of her medications could not explain the confusion. The plain film of the abdomen revealed multiple diffuse calcium-like deposits throughout the digestive tract. The plasma levels of lanthanum were higher than normal. The confusion resolved after discontinuation of the lanthanum carbonate. This case raises the problem of the potential role played by lanthanum tablet residue in the genesis or aggravation of diverticular flare-up and the problem of the potential permeability of the blood-brain barrier with lanthanum use in case of its digestive accumulation, leading to increased serum concentrations.

[Fabry disease's screening: Results from the first French survey on nephrologists habits]. / Dépistage de la maladie de Fabry : résultats de la première enquête française sur les pratiques des néphrologues.

Fabry disease is a systemic and genetic disorder resulting from an α-galactosidase A enzymatic deficiency leading to sphingolipid accumulation in lysosomes: it remains a rare and poorly-known disease. This study aimed to know the formation of nephrologists, their knowledge, and their habits both in terms of screening and management in this field. Answers form 152 nephrologists have been analyzed: few doctors directly managed Fabry disease patient (22 %) and 18 % have already made the diagnosis by their own. Formation seems to be insufficient and most of them did not fully know symptoms, as resources already available (associations, collecting database, etc.). Some indications for the treatment are also poorly known (mainly regarding end stage renal disease). Information is mainly provided by of firms' staff. A knowledge score was calculated: the kidney injury is also poorly known (less than 50 % of correct answers) even if 50 % of nephrologists performed appropriate testing and confirmation, around 65 % knew the symptoms, treatment indication and the main key points of the disease. Fabry disease is still an unknown disorder, unless early diagnosis tools and therapeutics exist to reduce its complications. Nephrology community has to invest more formation about symptoms, testing, and medical care.

Assessment of Renal Dysfunction Improves the Simplified Pulmonary Embolism Severity Index (sPESI) for Risk Stratification in Patients with Acute Pulmonary Embolism.

BACKGROUND: Whereas the major strength of the simplified pulmonary embolism severity index (sPESI) lies in ruling out an adverse outcome in patients with sPESI of 0, the accuracy of sPESI ≥ 1 in risk assessment remains questionable. In acute pulmonary embolism (APE), the estimated glomerular filtration rate (eGFR) can be viewed as an integrate marker reflecting not only previous chronic kidney disease (CKD) damage but also comorbid conditions and hemodynamic disturbances associated with APE. We sought to determine whether renal dysfunction assessment by eGFR improves the sPESI score risk stratification in patients with APE. METHODS: 678 consecutive patients with APE were prospectively enrolled. Renal dysfunction (RD) at diagnosis of APE was defined by eGFR < 60 mL/min/1.73 m² and acute kidney injury (AKI) by elevation of creatinine level >25% during in-hospital stay. RESULTS: RD was observed in 26.9% of the cohort. AKI occurred in 18.8%. A stepwise increase in 30-day mortality, cardiovascular mortality and overall mortality was evident with declining renal function. Multivariate analysis identified RD and CRP (C-reactive protein) level but not sPESI score as independent predictors of 30-day mortality. AKI, 30-day mortality, overall mortality, and cardiovascular mortality were at their highest level in patients with eGFR < 60 mL/min/1.73 m² and sPESI ≥1. CONCLUSION: in patients with APE, the addition of RD to the sPESI score identifies a specific subset of patients at very high mortality.

[Impact of the adjunction of boiled-egg during the chronic hemodialysis session on the nutrition state]. / Impact du renforcement de la prise en charge nutritionnelle du patient en hémodialyse chronique par ajout d'œufs durs en collation.

Denutrition for chronic hemodialysed patients is common and severe, often the first step of many complication and comorbidities. This work was aimed to study the impact of the adjunction of hard-boiled egg during six months, at the time of the hemodialysis session, if the classic nutritional support with oral nutritional supplements and intradialytic parenteral nutrition has failed. Required criteria were: Albuminemia, prealbuminemia and Moreau and Gaudry's score. Thirty-six patients have been included. During the six months, the following nutritional parameters have improved: Moreau and Gaudry's score decreased of 0.27, C reactive protein of 9.44 mg/L. Albuminemia improved of 3.53 g/L in average, pre-albuminemia of 0.2 g/L, and normalized Protein catabolic rate of 0.01 g/kg/day. Half of the patients were successful to stop the intradialytic parenteral nutrition. Protein adjunction with hard-boiled egg during chronic hemodialysis session, on top of the classic dietetic support has improved nutritional patient status.