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International audience; ObjectivesLupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN.MethodsWIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2–3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events.ResultsBetween 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI −1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups.ConclusionsNon-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares.Trial registration numberNCT01284725.

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

Summary We report a case of lactobacillus gasseri peritonitis in a patient treated by peritoneal dialysis. Streptococcus anginus and lactobacillus gasseri bacteria are commensal organisms of human oral, small intestinal, colic and vaginal mucous membranes. An infection with streptococcus anginosus during peritoneal dialysis, one responsible for an intra-abdominal abscess, has already been described, this type of streptococcus being widely associated with abscess formation. In contrast, no case of peritoneal infection with lactobacillus gasseri has ever been described. This bacterium is native to the mucous membranes, and colonizes the digestive tract of infants during childbirth, as they pass through the vaginal canal. It has local adaptation capacities, namely tolerance to acid pH, adhesion to the mucous membrane and resistance to bile salts. It is recognized as having an antimicrobial and probiotic function due to its production of bacteriocin, its local immunomodulatory role, its attenuation of the development of helicobacter pylori, its positive effect on the balance of the vaginal flora and its improvement of infectious diarrhea. This usually makes it an ally that contributes to our systemic balance but its irruption in the peritoneum has made it a pathogenic bacterium. The treatment of this peritoneal infection required a classic duration of treatment of organisms of digestive origin, i.e. 3 weeks

Recent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared with the general population, suggesting the possible value of a third booster dose. We characterized the humoral response after 3 doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD).Case series.69 French patients (38 HD and 31 PD) treated at a single center who received 3 doses of the BNT162b2 vaccine.Humoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least 3 weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 years [interquartile range (IQR), 53-76 years], 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7,554 [IQR, 2,268-11,736] AU/mL after the third dose. Three patients were nonresponders (anti-S1 antibody level 0.8 AU/mL), and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, 1 of the 3 initial nonresponders produced anti-spike antibody, and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe after a third vaccine dose.Observational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood.A third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.

Introduction Les patients dialysés ont une réponse vaccinale plus faible, et sont exposés à une morbimortalité plus importante que la population générale en cas d’infection par le SARS-CoV-2. Cependant, l’efficacité de la réponse vaccinale anti-SARS-CoV-2 reste peu étudiée dans cette population. Description L’objectif de cette étude était d’évaluer la réponse humorale au vaccin BNT162b2, et les facteurs associés à la réponse vaccinale chez des patients traités par hémodialyse (HD) et par dialyse péritonéale (DP). Méthodes Cette étude rétrospective a inclus 85 patients (n = 45 HD, n = 40 DP), ayant reçu deux doses du vaccin BNT162b2. La réponse vaccinale était évaluée par le titre d’anticorps anti-protéine spike, dosé au moins 10 jours après la deuxième dose vaccinale. Un titre d’anticorps anti-spike inférieur à 0,8 UI/mL correspondait à une non-réponse et un titre inférieur au 10e percentile (

Introduction Plusieurs cas de syndrome nephrotique secondaire a une nephropathie a lesions glomerulaires minimes (LGM) ont ete rapportes apres vaccination, notamment contre la grippe. Quelques cas commencent a etre rapportes avec les vaccins a ARNm anti SARS-CoV-2. Description Nous rapportons un cas de syndrome nephrotique survenant apres une premiere dose vaccinale anti SARS-CoV-2 (ChAdOx1 nCoV-19, Astra-Zeneca®). Methodes Un homme de 44 ans, sans antecedents medicaux, a ete hospitalise pour un tableau d’anasarque d’installation brutale survenant 3 semaines apres une premiere dose vaccinale. Le bilan biologique montrait un syndrome nephrotique (albumine 12,5 g/l, proteinurie 9,1 g/g) et une insuffisance renale aigue definie par une creatininemie a 187 μmol/l. Le titre d’anticorps anti-proteine Spike etait de 67 U/ml. La serologie anti-nucleocapside etait negative. Resultats La ponction biopsie renale montrait des lesions de hyalinose segmentaire et focale (HSF) avec trois « tip lesions » ( Fig. 1 ). L’evolution clinique et biologique (creatinine 73 μmol/l, albumine 34 g/l, proteinurie 27 mg/mmol) ont ete rapidement favorables sous corticotherapie 1 mg/kg/j. Conclusion La survenue d’un syndrome nephrotique dans les jours qui suivent la vaccination anti-COVID 19 souleve la question de l’imputabilite du vaccin et du mecanisme physiopathologique sous-jacent. La stimulation de l’immunite cellulaire T et une reponse cytokinique mediee par la vaccination pourraient contribuer a la survenue de lesions de LGM/HSF post-vaccination. Les resultats des etudes de pharmacovigilance restent necessaires pour determiner s’il existe un lien causal entre la survenue d’un syndrome nephrotique et la vaccination.

Introduction La COVID-19 peut etre associee a une hyalinose segmentaire et focale (HSF) collapsante nommee COVAN de mauvais pronostic. Description Nous rapportons quatre cas de patients ayant presente une aggravation de leur insuffisance renale chronique (IRC) dans les suites d’une infection COVID-19. Methodes Entre novembre 2020 et avril 2021, quatre patients d’origine Africaine âges de 47 a 74 ans, suivis dans notre service, ont ete hospitalises pour une aggravation de leur IRC. Leur nephropathie sous-jacente etait une nephroangiosclerose (n = 2), un diabete (n = 1), une HSF collapsante (n = 1) prouvee par ponction biopsie renale (PBR). Lors du suivi, leur clairance etait en moyenne de 47 mL/min/1,73 m2 avec une proteinurie negative ou Resultats Les patients ont ete hospitalises pour une aggravation majeure de leur IRC. A l’admission, la clairance moyenne etait de 18 mL/min/1,73 m2 associee a une proteinurie de rang nephrotique. Une infection COVID-19 a ete retrouvee dans les deux mois precedents chez deux des quatre patients. Tous avaient une serologie COVID-19 positive, ainsi que les alleles a risque du gene ApoL1 (homozygote G1/G1 ou heterozygote G1/G2). Deux patients ont eu une PBR retrouvant une HSF collapsante. La PBR n’a pas ete realisee chez les autres en raison d’une hypotrophie renale. Durant le suivi, deux patients sont restes stables, un a necessite le recours a l’hemodialyse et le dernier a ete traite par corticoides 0,5 mg/kg/j, permettant une diminution de la proteinurie et une amelioration partielle de la fonction renale. La particularite de notre serie est l’existence d’une IRC sous-jacente regulierement suivie. Il reste a determiner si la presence d’une IRC constitue un facteur favorisant la survenue d’une COVAN ( Tableau 1 ). Conclusion L’aggravation rapide d’une IRC et d’une proteinurie doit maintenant faire rechercher une anteriorite d’infection par la COVID-19. La COVAN est probablement sous-estimee chez ces patients pour lesquels la PBR n’est la plupart du temps pas effectuee.

International audience

Introduction La prise en charge therapeutique et l’evolution de la glomerulonephrite extra-membraneuse (GEM) sont peu decrits chez la femme enceinte. Le but de notre travail est de montrer l’efficacite de la ciclosporine dans ce contexte. Methodes Nous avons collige trois cas de GEM, chez des femmes enceintes entre 11 SA et 15 SA, dont une grossesse gemellaire bi-choriale bi-amniotique obtenue par FIV. Resultats obtenus ou attendus La proteinurie initiale etait de 2,56 a 10 g/24 h et l’albumine plasmatique de 16 g/l a 28 g/l. La fonction renale etait normale. Une ponction biopsie renale (PBR) transjugulaire a ete pratiquee chez une patiente, les deux autres ont beneficie d’une PBR transparietale. Le caractere primitif de la GEM etait atteste par la presence d’anticorps anti-PLA2R chez une patiente et sur un bilan etiologique negatif chez les deux autres. Un traitement par corticoides (20 mg/jour) et ciclosporine (de 150 mg/j a 300 mg/j, selon les dosages plasmatiques) a ete initie. Les dosages de ciclosporinemie sont restes compris entre 80 et 100 μg/l. Une remission a ete observee apres 4 a 16 semaines de traitement avec une baisse de proteinurie jusqu’a 0,15 g/24 h. Il n’y a pas eu de complications infectieuses maternelles ou fœtales. Sont survenus une menace d’accouchement premature a 36 SA + 3 jours, facilement resolutive et un accouchement a 36 SA pour la grossesse gemellaire. Tous les enfants etaient de bon poids. La remission clinique et biologique s’est maintenue (rechute transitoire chez une patiente dans un contexte infectieux cutane). Actuellement les 3 patientes sont en remission complete, a fonction renale preservee sous faible dose de corticoides (10 mg/jour) et ciclosporine. Conclusion Au total, la ciclosporine a montre son efficacite dans l’obtention et le maintien de la remission de la GEM primitive de la femme enceinte. Il s’agit donc d’une bonne alternative a d’autres therapeutiques difficilement applicables au cours de la grossesse.

Background Henoch-Schonlein purpura, more recently renamed immunoglobulin A vasculitis (IgAV), is a systemic vasculitis characterized by IgA deposits. The current markers used to assess IgAV inaccurately evaluate the risk of nephritis occurrence and its long-term outcomes. The current study assessed biomarkers of nephritis outcomes. Methods This French multicentre prospective study enrolled 85 adult patients at the time of disease onset. Patients were assessed for clinical and biological parameters and re-examined after 1 year. Immunoglobulins, cytokines, IgA glycosylation, IgA complexes and neutrophil gelatinase-associated lipocalin (NGAL) concentrations were assessed in blood and urine. Results We identified 60 patients with IgAV-related nephritis (IgAV-N) and 25 patients without nephritis (IgAV-woN). At the time of inclusion (Day 1), the serum levels of galactose-deficient IgA1 (Gd-IgA1) and urinary concentrations of IgA, IgG, IgM, NGAL, interleukin (IL)-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were higher in the IgAV-N patients than in the IgAV-woN patients (P

Supplemental Digital Content is available in the text, The optimal treatment for pure membranous lupus nephritis (MLN) remains undetermined. Rituximab constitutes a promising therapeutic option for lupus nephritis and is currently being evaluated for use in idiopathic membranous nephritis. We retrospectively analysed the efficacy and tolerance of rituximab as a monotherapy in the induction treatment of pure MLN. We retrospectively investigated SLE patients with biopsy-proven pure class V lupus nephritis presenting with a protein-to-creatinine ratio of at least 2 g/g and treated with rituximab as monotherapy. A background low dose of corticosteroids (≤20 mg/day) was allowed, as was hydroxychloroquine; higher doses of steroids and/or immunosuppressive drugs fell under the exclusion criteria. Remission status was evaluated at baseline and 6, 12, and 24 months after rituximab. The study included 15 patients (13 women, median age 37 years, 27% with extra-renal manifestations, median SLE duration 1.5 years). The median protein-to-creatinine ratio was 4.9 g/g, 80% of the patients had nephrotic-range proteinuria, the median serum albumin was 24 g/L, the median serum creatinine was 0.7 mg/dL, and the median eGFR was 122 mL/min/1.73 m2. The median follow-up was 29 months (6–112 months). Treatment failure occurred in 2 patients. However, remission was recorded in the remaining 13 (87%, complete remission in 8 patients) with a median time to remission of 5 months. Median proteinuria decreased from 4.9 g/g to 0.16 g/g at month 12 and to 0.11 g/g at month 24. Median serum albumin increased to 36.5 g/L at month 24, and all patients had serum albumin levels greater than 30 g/L at month 12. Renal function remained stable in all patients. Relapse of proteinuria was recorded in 3 patients (at 12, 29, and 34 months). No patients experienced serious adverse events. Rituximab as monotherapy may represent an effective treatment for pure MLN with an excellent tolerance profile.

Introduction La glomerulonephrite extra-membraneuse GEM est une cause majeure de syndrome nephrotique chez l’adulte, elle est moins decrite chez la femme enceinte en particulier sa prise en charge therapeutique immunosuppressive. Le but de notre travail est de montrer l’efficacite de la ciclosporine chez la femme enceinte atteinte de GEM primitive. Methodes Etude descriptive nous avons collige entre l’annee 2008 et 2019, trois cas de GEM survenant chez des femmes enceintes dont l’âge gestationnel moyen au moment du diagnostic etait de 13 SA + 3 jours pour un âge moyen de 32,6 ans. Resultats obtenus ou attendus La proteinurie moyenne etait a 5,52 g/24 H lors de la decouverte du syndrome nephrotique et l’albuminurie moyenne a 23 g/l. Toutes nos patientes ont eu une PBR ; le caractere primitif de GEM etait attribue a la presence d’anticorps anti-PLA2R chez une patiente et sur un bilan etiologique negatif chez les autres. Un traitement a base de corticoides a faible dose associe a la ciclosporine a ete initie chez toutes nos patientes au cours d’un âge gestationnel moyen de 18 SA, une remission etait obtenue a 8 semaines de traitement en moyenne avec une baisse de la proteinurie de 24 h jusqu’a 0,15 g/24 H. La remission clinique et biologique est maintenue en post-partum hormis une qui a presente une rechute dans un contexte infectieux cutane resolu apres maitrise du syndrome infectieux et majoration de l’immunosuppression. Le dosage de la cyclosporine dans le sang est reste stable. Actuellement toutes nos patientes sont en remission complete, a fonction renale preservee sous faible dose de corticoides et cyclosporine. La duree moyenne de la ciclosporine est de 5 ans. Conclusion Dans notre serie, la ciclosporine a montre son efficacite dans le maintien de la remission du syndrome nephrotique dans la GEM primitive survenue chez des femmes enceintes, avec un pronostic materno-fœtal satisfaisant.

The development of well-tolerated and effective therapies that target the pathogenesis of membranous nephropathy (MN) would be useful. Our objective was to evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients treated with rituximab for idiopathic MN. Anti-PLA2R antibodies in serum and PLA2R antigen in kidney biopsy were assessed in 10 and 9 patients, respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6 and 12 months, respectively. At 6 months, 2 patients achieved complete remission (CR) and 12 partial remission (PR; overall renal response, 50%). At 12 months (n = 23), CR was achieved in 6 patients and PR in 13 patients (overall renal response, 82.6%). Three patients suffered a relapse of nephrotic proteinuria 27–50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD estimated glomerular filtration rate 2) is an independent factor that predicts lack of response to rituximab. Anti-PLA2R antibodies were detected in the serum of 10 patients, and PLA2R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up sera. In this retrospective study, a high rate of remission was achieved 12 months after treatment.

It is well known that lesions morphologically identical with focal segmental glomerulosclerosis (FSGS) may appear in IgA nephropathy (IgAN). Capsular adhesions without underlying abnormalities in the tuft, often the first sign of FSGS, are frequent in IgAN. In this retrospective study, a new cohort of 128 adult patients with IgAN was used to validate the new Oxford classification system of IgAN, and shown to have highly significant associations with clinical and outcome parameters. We then used these patients to determine the extent to which IgAN could be accounted for in terms of FSGS. Some form of lesion consistent with FSGS, notably hyalinosis and collapsing glomerulopathy, was found in 101 of these patients. No glomerular lesions were found in 16 patients, and 11 had mild lesions not definable as FSGS. Those with FSGS had significantly worse renal survival at 80 months than those without. Comparison of pure forms of FSGS (excluding collapsing glomerulopathy) with cases of FSGS having other glomerular lesions (mesangial hyperplasia, endocapillary hypercellularity, glomerular necroses, extracapillary proliferation) revealed that those with FSGS and other superimposed lesions did significantly worse than cases of pure FSGS at 80 months following diagnosis. Importantly, patients with pure FSGS had relatively poor survival even without other superimposed glomerular abnormalities. Thus, the majority of cases of IgAN can be interpreted as representing one or another variant of FSGS. Hence, interpreting IgAN in terms of FSGS emphasizes the role that podocyte lesions may play in the pathogenesis and progression of this disease.

International audience; BACKGROUND: The proportion of diabetic patients undergoing haemodialysis is rapidly increasing. Glucose control among such patients is difficult to assess. We aimed to evaluate the clinical performance of a continuous glucose monitoring system (CGMS) in type 2 diabetic patients on chronic haemodialysis. METHODS: We used a 4-day CGMS to monitor glucose levels in 19 haemodialysed type 2 diabetic patients (HD T2) including 2 days with and 2 days without dialysis session, and 39 non-HD T2 in a double-centre study. RESULTS: The glucose concentration according to the glucose meter and CGMS were correlated in HD T2 patients (r = 0.90, P < 0.0001) and in non-HD T2 patients (r = 0.81, P < 0.0001). The relative absolute difference (RAD) between glucose determined by a glucose meter and glucose determined by the CGMS did not differ between HD T2 and non-HD T2 patients (9.2 +/- 10.5 vs. 8.2 +/- 7.6%; P = 0.165). Glycated haemoglobin (A1c) and mean glucose concentration were strongly correlated in non-HD T2 patients (r = 0.71; P < 0.0001) but weakly correlated in HD T2 patients (r = 0.47; P = 0.042). Fructosamine was correlated with the mean glucose concentration in non-HD T2 (r = 0.67; P < 0.0001) but not in HD T2 patients (r = 0.04; P = 0.88). CONCLUSION: CGM is a validated marker of glycaemic control in HD diabetic patients. This tool showed that A1c and fructosamine, despite being good markers of glycaemic control in non-HD diabetic patients, are of poor value in HD diabetic patients.

Introduction Le traitement specifique des GEM lupiques pures est mal codifie. Le rituximab a un interet reconnu pour certaines glomerulonephrites lupiques proliferatives actives et est en cours d’evaluation pour les GEM idiopathiques. L’objectif de l’etude etait d’evaluer l’efficacite et la tolerance du rituximab en monotherapie chez les patients presentant une GEM lupique pure. Patients et methodes Etude retrospective multicentrique nationale incluant les patients ayant une GN lupique classe V pure de l’ISN/RPS 2003, un ratio proteinurie/creatininurie (RPC) d’au moins 2 g/g et ayant beneficie d’un traitement d’induction par rituximab seul ou associe a une corticotherapie a faible dose (≤ 20 mg/j). Le statut de remission renale a ete analyse a 6, 12 et 24 mois du traitement par rituximab. La remission complete (RC) etait definie par RPC Resultats Quatorze patients (13 femmes) d’âge median de 37 ans ont ete inclus. Le RPC median etait de 4,4 g/g (> 3 g/g pour 79 %). L’albuminemie mediane etait de 25,5 g/L. La creatininemie mediane de 0,7 mg/dL (DFG estime median : 121,5 mL/min/1,73 m2 [67–158]). Le suivi median a ete de 29 mois. Deux patients ont presente un echec de traitement. Une remission a ete obtenue chez les 12 autres (86 % de la cohorte, RC chez 8 patients) apres un delai median de 5 mois. Il existait une reduction de la proteinurie mediane a 0,02 g/g et tous les patients avaient une albuminemie superieure a 30 g/L a 12 mois. La fonction renale est restee stable chez tous. Trois ont presente une rechute a 12, 29 et 34 mois du traitement. Aucun effet secondaire severe n’a ete rapporte. Discussion Le rituximab en monotherapie pourrait constituer une option therapeutique efficace et bien toleree pour les GEM lupiques pures. Conclusion Une etude prospective randomisee est necessaire afin de confirmer sa place reelle dans cette indication.

Introduction Les glomerulopathies a depots de C3 (GC3) regroupent un ensemble heterogene de glomerulopathies chroniques qui ont recemment ete individualisees au sein des glomerulonephrites membrano-proliferatives (GNMP) [1] , [2] . Certaines formes de GC3 sont associees a des mutations des genes regulant l’activation de la voie alterne du complement [3] . Observation Nous rapportons le cas d’une patiente transplantee renale en 2005 a l’âge de 42 ans apres evolution defavorable d’une glomerulopathie d’etiologie indeterminee associee a des stigmates biologiques de microangiopathie thrombotique. Le bilan etiologique initial avait mis en evidence une consommation de la voie alterne (baisse du C3 et du facteur B avec un C4 normal) associe a un deficit quantitatif du facteur I sans anticorps anti-C3 convertase de la voie alterne. Le mecanisme en cause etait une mutation homozygote jamais rapportee au niveau de l’exon 10. Dans les suites de la transplantation renale qui se deroule sans incident notable (creatinemie 97 μmol/L en 2009), la patiente beneficie en 2009 d’une premiere ponction biopsie du greffon pour l’apparition d’une proteinurie a 1,3 g/j dans un contexte d’apparition de DSA. Cet examen met en evidence une GNMP avec proliferation endocapillaire associee a un marquage exclusif de C3 au niveau sous-endothelial, mesangial et parietal. Devant la parfaite stabilite de la fonction renale et la diminution de la proteinurie sous IEC, une simple surveillance est preconisee. Le bilan immunologique en 2009 retrouve des anomalies identiques a celles decrites lors de la prise en charge initiale. Deux nouvelles biopsies du greffon en 2014 et 2015 montrent une parfaite stabilite des lesions histologiques alors que la proteinurie reste inferieure a 0,3 g/j et la fonction renale stable (96 μmol/L en 2016) Discussion Des mutations heterozygotes du facteur I peuvent etre associees a des GC3 mais une mutation homozygote du facteur I qui est habituellement associee a des infections recidivantes constitue une observation exceptionnelle et une cause inhabituelle de GC3. Conclusion Apres plus de 10 ans de greffe renale sans traitement specifique (anti-C5, echanges plasmatiques), la recidive de GC3 sur le greffon en rapport avec une mutation homozygote du facteur I peut etre purement histologique sans traduction clinique.

Microscopic polyangiitis, granulomatosis with polyangiitis, Churg-Strauss syndrome and focal necrotizing glomerulonephritis are severe systemic vasculitides associated with circulating antineutrophil cytoplasmic antibodies (ANCA). Several studies reported that some malignancies can develop in these patients during follow-up, but few studies have considered the association and role of pre-existing cancers, at least in a fraction of patients. Herein, we report five patients with ANCA-associated diseases who had associated lung carcinomas or were diagnosed within 2 years after vasculitis onset. We discuss the putative role of tumor antigen in driving the auto-immune response.

Kinetics of 125 I-β 2 -microglobulin turnover in dialyzed patients. The kinetics of β 2 -microglobulin (β 2 m) were studied in 17 anephric or functionally anephric hemodialyzed patients and five healthy subjects as controls. Highly purified β 2 m was radiolabeled with 125 I and infused into patients. The radioactivity in plasma and dialysis fluids was measured during a week including two or three dialysis sessions. Patients were classified in four groups according to treatment: hemodialysis on Cuprophan (N = 5) or on AN69 membranes (N = 5), hemofiltration (N = 4) and CAPD (N = 3). Plasma activity was fitted to a three compartment model. In controls almost 100% of the radioactivity was recovered in urine within 96 hours and there was no extrarenal catabolism. In patients the fractional catabolic rate ranged from 0.0008 to 0.0022 min -1 versus 0.026 to 0.047 min -1 in controls. The synthetic rate was within the range of values from controls in 10 patients but higher in the seven others. It was correlated with plasma β 2 m concentration. Kinetic data indicate a retention of intact β 2 m. The original model was therefore modified with an additional compartment representing β 2 m captation. The amount of capted β 2 m was more elevated in hemodialyzed patients than in patients treated by hemofiltration or CAPD, in whom it could reach 5 mg/kg/day. Hemofiltration or CAPD may eliminate about 30 to 100% of β 2 m produced and therefore contribute to the low captation amount of these patients, as compared with that of patients treated by hemodialysis.

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.

The kinetics of 131I-beta2-microglobulin (beta2-M) were studied using external total body gamma counting in a low noise chamber after administration of trace doses of radioactivity (4 microCi) in 14 uremic patients treated by either hemodialysis or hemofiltration. Data were collected over a 1 week period that included 3 dialysis sessions. The following artificial membranes were used: Cuprophan, polyacrylonitrile AN69, polysulfone, polymethylmethacrylate (PMMA), and polyamide. Radiolabeled beta2-M excretion by an extrarenal route was nearly nonexistent. The 131I-beta2-M half-life was between 2.4 and 8 days, shorter in patients with residual diuresis. A mean removal of 153+/-33 mg/L of beta2-M was obtained per dialysis session with a highly permeable membrane. A hemofiltration session (25 L exchange per session) was slightly more efficient in removing beta2-M than a 4 h hemodialysis session with the same AN69 highly permeable membrane. The amounts of 131I-beta2-M binding on the membranes, expressed as beta2-M equivalents, were 0, 16, 54, 58, and 59 mg/m2 for Cuprophan, polysulfone, polyacrylonitrile AN69, polyamide, and PMMA, respectively. In conclusion, the decrease of total body gamma counting directly reflected the beta2-M breakdown and removal in hemodialysis patients. Intact beta2-M was removed by convection with synthetic, highly permeable membranes. In addition, membrane adsorption accounted for 15% (polysulfone) to near 100% (PMMA) of the beta2-M removal per session. Adsorption was of the same magnitude regardless of the dialysis technique in use, indicating a membrane saturability process. None of the currently available dialysis procedures based on a 3 sessions per week schedule can balance beta2-M generation.

Membrane regulatory molecules normally prevent complement activation by autologous cells, therefore we compared the membrane control system of human lymphoid cell lines which activate or not human complement through the alternative pathway (AP). Membrane expression of decay-accelerating factor (DAF), membrane cofactor protein (MCP), complement receptors (CR)1, CR2 and H was measured either by radioimmunoassay or enzyme-linked immuno-sorbent assay on cell lysates. Soluble extracts of isolated membranes were tested functionally for their ability to accelerate the decay of C3bBb C3-convertase and allow the cleavage of C3b by factor I. Both regulatory functions were detected in solubilized membranes of Ramos cells, which do not activate the AP, as well as on the potent AP activator, Raji. Raji cells were found to express CR2, DAF and MCP molecules, while MCP was the only known regulatory protein detected on Ramos cells which expressed neither CR1, nor CR2, H or DAF. The I-cofactor activity of both Raji and Ramos cells was immunoprecipitated by anti-MCP, but the decay-accelerating activity was not adsorbed by anti-DAF nor by any of the available antibodies. Two EBV genome-negative cell lines (BJAB, BL41) were tested before and after in vitro conversion by EBV. As previously shown, EBV-converted cell lines activate the AP more efficiently than EBV− cell lines. At the same time, EBV superinfection induces an increase of both AP regulatory functions of cell membranes and enhances the expression of DAF, MCP and CR2. The results of this study show that complement activation by lymphoid cell lines is not related to an impaired autologous control of these cells, but that the expression of regulatory molecules increases together with the appearance of activating structures on the cell surface. Our results also suggest the occurrence of a new factor involved in the decay-accelerating activity on BL lines.

The number of C3b receptor (CR1) molecules on erythrocytes is genetically determined by two codominant autosomal alleles. The genetic polymorphism of CR1 expression correlates with a Hind III restriction fragment length polymorphism (RFLP) of the CR1 gene. The relative frequency of individuals homozygous for the allele coding for low CR1 numbers is approximately 5% of the normal population. CR1 numbers/erythrocytes are significantly decreased in symptomatic HIV-infected individuals. Decreased CR1 expression correlates with the severity of disease. The present study investigated the CR1 genomic Hind III RFLP-related polymorphism in 79 HIV-infected individuals and 84 healthy subjects. Allele frequencies were found to be similar in both populations. Thus, there is no susceptibility nor resistance to HIV-infected linked to the CR1 gene. Defective expression of CR1 in HIV-infected patients is acquired through central and/or peripheral mechanisms.

The role of genetic factors in decreased expression of CR1 in patients with systemic lupus erythematosus (SLE) was investigated by assessing the frequency of genotypes determining the numbers of CR1 on erythrocytes obtained from 52 patients with SLE and from 84 normal individuals. The expression of CR1 was quantitated using flow cytometry. Genotypes were determined by analyzing the CR1 gene restriction fragment length polymorphism using the CR1.1 complementary DNA probe and the Hind III restriction enzyme. In normal subjects, the distribution of the HH, HL, and LL genotypes fit the Hardy-Weinberg law. The frequency for the H allele did not differ between the 2 groups. No individual homozygous for the LL genotypes was found among the SLE patient population. Taken together, data from this and previous studies indicate an under-representation of the LL homozygous genotype in patients with SLE. SLE patients expressed decreased numbers of CR1 per erythrocyte within each genotype compared with these numbers in normal subjects. The results suggest that defective expression of CR1 in SLE patients is acquired and that the presence of the L allele is not linked to a genetic susceptibility for SLE.