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Integrin Subunit Alpha 8 gene (ITGA8) encodes an integrin chain that is known to be critical in the early stage of the kidney development. Bi-allelic pathogenic variants in ITGA8 are associated with bilateral renal agenesis, as well as anomalies involving urogenital system. Here, we report two unrelated patients presenting with slowly progressing chronic kidney disease associated with bilateral renal hypodysplasia carrying homozygous loss of function variants in the ITGA8 gene. These results broaden the clinical and genotypic spectrum of ITGA8 defects, revealing the high and unexpected degree of phenotypic heterogeneity of this autosomal recessive disease. Our study emphasizes the usefulness of Next-Generation Sequencing in unraveling the genetic cause of chronic kidney disease of unknown etiology, and raises the question of genetic modifiers involved in the variation of the phenotypes associated with autosomal recessive ITGA8 pathogenic variants.

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.

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.

We report the case of a patient followed for a mixed connective tissue disease with signs of systemic sclerosis and systemic lupus, who presented an acute renal failure with severe neurological symptoms (confusion, obnubilation) and hypertension. The distinction between scleroderma renal crisis and lupus nephritis was challenging and hence, the decision to use or not high dose of corticosteroids. Kidney biopsy was of major importance for the diagnosis and therapeutic strategy. The diagnosis of neurological symptoms was also made difficult given the clinical presentation and the results of imaging. Neurolupus, malignant hypertension, or posterior reversible encephalopathy syndrome were the evoked diagnosis.

Background Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis. Methods We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment. Results We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up. Conclusions This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule.

Objective The optimal induction therapy for severe glomerulonephritis of ANCA-associated vasculitis (AAV) is debated. We compared the efficacy of glucocorticoid and rituximab (RTX) or CYC induction therapy for severe AAV-related glomerulonephritis and evaluated the potential benefit of plasma exchange (PE) as adjunct therapy to CYC. Methods This retrospective, multicentre study included AAV patients with severe renal active disease (serum creatinine level ≥350 µmol/l and/or estimated glomerular filtration ratio ≤15 ml/min/1.73 m2). Propensity-score analysis was used to adjust for potential confounders. Results Between 2005 and 2017, 153 patients with AAV-related glomerulonephritis were studied (96 [60%] men; mean [s.d.] age 63 [13.1] years): 19 (12%) were treated with RTX and 134 (88%) with CYC. Remission rates did not differ between RTX- and CYC-treated groups. Although more patients with RTX than CYC were dialysis-free at month (M) 12 (79% vs 68%), the difference was not significant after adjustment. Among 134 patients with CYC-treated glomerulonephritis, 76 (57%) also had PE. M3 and M6 remission rates were comparable for weighted CYC groups with or without PE. For weighted groups, the dialysis-free survival rate with CYC was higher with than without PE at M6 (72% vs 64%; odds ratio 2.58) and M12 (74% vs 60%; odds ratio 2.78) reaching statistical significance at M12. Conclusion We could not find any difference between RTX and CYC as induction therapy for patients with severe AAV-related glomerulonephritis. In patients receiving CYC induction regimen, the addition of PE conferred short-term benefits with higher dialysis-free rate at M12.

Background Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. Methods In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. Results We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. Conclusions Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.

OBJECTIVE: This study was undertaken to characterize kidney and urine antibody-secreting cells (ASCs) from patients with active lupus nephritis, before and after induction therapy. METHODS: We included patients with biopsy-proven active lupus nephritis and performed anti-CD138 staining of kidney biopsy samples to visualize ASCs. We performed single-cell gene expression profiling on sorted ASCs from fresh biopsy samples using multiplex reverse transcriptase-polymerase chain reaction. We used a gene set that allowed for the study of ASC maturation from plasmablasts to long-lived plasma cells. We quantified urine ASCs from untreated patients with lupus nephritis at diagnosis and after 6 months of prospective follow-up during induction therapy. RESULTS: The number of kidney CD138+ ASCs in 46 untreated patients with lupus nephritis was correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASCs from 3 untreated patients had a plasmablast molecular signature; in contrast, in 4 patients with refractory lupus nephritis, the kidney ASCs were mainly long-lived plasma cells, representing an ASC transcriptional profile similar to that in the bone marrow of 2 healthy donors. Some urine ASCs with a plasmablast signature were detected in patients with untreated active lupus nephritis. The presence of urine ASCs at 6 months was associated with treatment failure. CONCLUSION: Our results suggest potential for ASC-directed therapy in refractory lupus nephritis.

International audience; Background: Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined.Methods: In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being.Results: In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32 years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = - 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS.Conclusions: This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.

Multicentric carpo-tarsal osteolysis (MCTO) is a rare osteolysis syndrome mainly involving carpal and tarsal bones usually presenting in early childhood. MCTO has autosomal dominant inheritance with heterozygous mutation in the MAFB gene. The skeletal disorder is often associated with chronic kidney disease. Data on clinical characterization and best treatment option of MCTO-associated nephropathy are scarce and mostly limited to case reports. With the aim to better define the phenotype and long-term outcomes of MCTO-associated nephropathy, we launched an online survey through the Workgroup for hereditary glomerulopathies of the European Rare Kidney Disease Network (ERKNet). Overall, we collected clinical and genetic data of 54 MCTO patients, of which 42 previously described and 12 new patients. We observed a high rate of kidney involvement (70%), early age of kidney disease onset, nephrotic-range proteinuria, and a kidney survival around of 40% at long-term follow-up. Our finding confirmed the heterogeneity of clinical manifestations and widen the spectrum of phenotypes resulting from MCTO-associated nephropathy. Furthermore, we report the first case of complete remission after treatment with cyclosporine A. We demonstrated that multidisciplinary care is essential for MCTO patients and early referral to nephrologists is therefore warranted to facilitate prompt treatment.

Background Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype. Aims This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis. Methods Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death. Results Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29–7.34), performance status (OR 1.40, 1.05–1.87), use of morphine (OR 2.51, 0.87–7.24), abdominal guarding (OR 3.08, 1.01–9.37), ileus (OR 2.29, 0.98–5.32), melena (OR 2.74, 1.17–6.42), increased leukocytes (per G/L, OR 1.05, 1.00–1.10), low hemoglobin (per g/dL, OR 0.80, 0.71–0.91) and increased CRP (log mg/L, OR 1.21, 0.94–1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well. Conclusions Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.

BACKGROUND AND AIMS Little is known about the long-term outcome during adulthood of childhood onset idiopathic nephrotic syndrome (INS). We aimed to determine which patients require long-term follow up after transition, to identify risk factors of relapse and to analyze treatment strategies. METHOD In this monocentric retrospective study, we included all patients admitted in our adult nephrology department with INS diagnosed during childhood. Patients who reached kidney failure during childhood were excluded. Data regarding the outcome at adult age were obtained through clinical database and medical charts. RESULTS Eighty-two patients (male/female = 2/1) were included, with a median age at diagnosis of 3.9 years (1.2–16.5). Sixty-eight patients had steroid-sensitive INS, including 52 with steroid-dependent nephrotic syndrome or frequently relapsing nephrotic syndrome. Fourteen patients had steroid-resistant nephrotic syndrome. A total of 89% of patients received corticosteroid sparing treatment during childhood. Median follow-up during adulthood was 6.2 (0.3–25) years. A total of 71% of patients experienced at least one relapse during adulthood. The total number of relapses during childhood and the number of relapses per year during childhood, reflecting disease activity, were significantly higher in patients who experienced relapses during adulthood than in patients who did not (Figure 1). The risk of relapse during adulthood was also significantly associated with the need for immunosuppressive regimen at the time of the transition visit (P = 0.002). To promote the successful transition of young people, we propose to organize a transition visit where the adolescent/young adult is seen jointly by pediatric and adult nephrologists, as it was done for 68% of patients in this study. The relapse rate was significantly lower (50%) in the subgroup of patients who had such a transition visit. We also found that relapse during the first two-years of adulthood follow-up was significantly associated with the risk of further relapse, highlighting the need for a close follow-up during the transition period. A total of 45% of patients received corticosteroid sparing treatment during adulthood, mainly mycophenolate mofetil (N = 23), calcineurin inhibitors (N = 21) and rituximab (N = 12). The main complications were high blood pressure (20/82, 26%) and osteopenia (19/26, 73% when bone densitometry was performed). Only one thrombo-embolic event and three severe infections were reported. At last follow-up, median eGFR was 87.1 (23.4–150.8) mL/min/1.73 m². CONCLUSION The incidence of relapses in adulthood is high in patients with active disease during childhood. A long-term follow-up is mandatory in these patients. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent and should be carefully monitored during adulthood. Transition visit should be carefully coordinated to prevent the risk of nonadherence.

BACKGROUND AND AIMS Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with an induction immunosuppressive therapy (IST), followed by a maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST for proliferative LN is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2–3 years in proliferative LN was non-inferior to IST continuation for 2 more years. METHOD WIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centres. Patients on maintenance IST with azathioprine or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and those who were taking hydroxychloroquine were randomized (1:1) between two groups: IST continuation and IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events, kidney function, disease activity, corticosteroid exposure, patient-reported outcome and medico-economic impact. RESULTS Between 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group and 48 in the IST discontinuation group. In the per-protocol population, a relapse of proliferative LN occurred in 5/40 (10.4%) patients with IST continuation, and in 12/44 (25%) patients with IST discontinuation (difference 14.8%, 95% CI [−1.9; 31.5]). Noninferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (P = 0.092). Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 versus 14/44 patients; P = 0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups. CONCLUSION Noninferiority of maintenance IST discontinuation after 2 to 3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flare.

Background Little is known about clinical characteristics and kidney outcomes in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD). Methods We conducted a retrospective multicentre study with a centralized histological review to analyse the presentation, therapeutic management and outcome of 24 patients suffering from IBD-associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD. Results Crohn’s disease and ulcerative colitis accounted for 75 and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9 years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. The urinary protein:creatinine ratio exceeded 100 mg/mmol in 70.8% of patients (mean 254 mg/mmol). Estimated glomerular filtration rate (eGFR) was >60 mL/min/1.73 m2 in 13/24 patients and only 1 patient required dialysis. In the Oxford mesangial hypercellularity, endocapillary cellularity, segmental sclerosis and interstitial fibrosis/tubular atrophy with crescents classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1–2 and 38% C1–2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2 years, 4 patients (16.7%) had a poor kidney outcome: end-stage renal disease (n = 3) or a >50% decrease in eGFR from initial values (n = 1). A similar evolution was observed in patients with primitive IgAN. Conclusions This first case series suggests that IBD-associated IgAN has frequent inflammatory lesions at onset and variable long-term outcomes.

Background Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population. Methods Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded. Results Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID_Pos) and 39 were not. Compared with uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50% versus 21%; P = .046) and were more often scheduled on the Monday–Wednesday–Friday (MWF) shift (86% versus 39%; P = .002). Moreover, COVID_Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients {median 24 BAU/mL [interquartile range (IQR) 3–1163] versus 435 [99–2555]; P = .001} and lower neutralization titres [median 108 (IQR 17–224) versus 2483 (481–43 908); P = .007]. Anti-S and neutralization antibody titres are correlated (r = 0.92, P 284 BAU/mL got infected. Ten of 14 COVID_Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease. Conclusions Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.

Summary: Background: Erythrocytosis is a hematological disorder usually related to hematopoietic stem cell somatic mutations. However, unexplained erythrocytosis remains frequent. In this study, we evaluated the involvement of IgA1, a regulator of erythropoiesis also implicated in IgA nephropathy (IgAN) pathophysiology, in unexplained polycythemia/erythrocytosis (PE) of IgAN patients. Methods: IgAN-PE patients’ serum was collected, analyzed and used to study IgA1 effect on proliferation and differentiation of erythroid progenitors. Hematological parameters of transgenic mice for human alpha1 heavy chain were studied. Multicentric observational cohorts of chronic kidney disease (CKD) patients, including both native kidney diseases and renal transplants, were studied to analyze patient hemoglobin levels. Findings: We retrospectively identified 6 patients with IgAN and unexplained PE. In large CKD cohorts, IgAN was associated with PE in 3.5% of patients (p

Despite improvement in the specific treatment, clinical and anatomo-functional central nervous system (CNS) abnormalities of various severities are still observed in cystinosis patients. Patients who develop CNS complications today have a worse compliance to cysteamine treatment. Radiological studies have shown that cortical or central (ventriculomegaly) atrophy is observed in more than two thirds of cystinosis patients’ magnetic resonance imaging (MRI) and correlates with the intelligence quotient score. Half of cystinosis patients have marked aspecific white matter hyperintensities. The development of advanced neuroimaging techniques provides new tools to further investigate CNS complications. A recent neuroimaging study using a voxel-based morphometry approach showed that cystinosis patients present a decreased grey matter volume in the left middle frontal gyrus. Diffusion tensor imaging studies have shown white matter microstructure abnormalities in children and adults with cystinosis, respectively in areas of the dorsal visual pathway and within the corpus callosum’s body. Finally, leucocyte cystine levels are associated with decreased resting cerebral blood flow, measured by arterial spin labelling, in the frontal cortex, which could be associated with the neurocognitive deficits described in these patients. These results reinforce the relevance of neuroimaging studies to further understand the mechanisms that underline CNS impairments.

Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P 6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.

The optimal duration of eculizumab treatment in patients with atypical hemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicenter open-label study to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean treatment duration, 16.5 months). Twenty-eight patients (51%) had rare variants in complement genes, mostly in MCP (n = 12; 22%), CFH (n = 6; 11%), and CFI (n = 6; 10%). At eculizumab discontinuation, 17 (30%) and 4 patients (7%) had stage 3 and 4 chronic kidney disease, respectively. During follow-up, 13 patients (23%; 6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female sex and presence of a rare variant in a complement gene were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during a previous episode of acute aHUS was not. In addition, increased sC5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers with a complement gene rare variant, both by log-rank test and in multivariable analysis. Of the 13 relapsing patients, all of whom restarted eculizumab, 11 regained their baseline renal function and 2 had a worsening of their preexisting chronic kidney disease, including 1 patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment. This trial was registered at www.clinicaltrials.gov as #NCT02574403.

Background Apheresis is the gold standard for idiopathic nephrotic syndrome (INS) relapse after transplantation, but it remains unknown whether such treatment is useful for adults with refractory INS on native kidneys. Methods This retrospective study included patients older than 16 years with biopsy-proven refractory (persistent nephrotic syndrome on corticosteroids plus at least 1 immunosuppressive drug) INS treated by apheresis and followed for at least 3 months. Results Between September 1997 and January 2020, 21 patients (focal segmental glomerulosclerosis: 12, minimal change nephrotic syndrome: 9, men: 67%, median age: 34 years) were identified. At last follow-up (12 months), 7 of 21 patients were in complete or partial remission. Remission was associated with older age (51 vs. 30 years, P = 0.05), lower proteinuria (3.9 vs. 7.3 g/d, P = 0.03), and lower estimated glomerular filtration rate (eGFR) (28.0 vs. 48.5 ml/min per 1.73 m2, P = 0.05) at apheresis. The need for dialysis before apheresis (odds ratio [OR] 22.0 [1.00–524], P = 0.026), age ≥50 years (OR: 22.6 [1.00–524], P = 0.006), a marked (>4.5 g/d) decrease in proteinuria (OR: 9.17 [1.15–73.2], P = 0.041), and a short (, Graphical abstract

Background and Aims Little is known about the long-term outcome of childhood idiopathic nephrotic syndrome (INS), in particular long-term complications, rate of relapses, frequency of prolonged steroid (S) and immunosuppressive treatment (IS). The choice of immunosuppressive drug remains discussed. Our aim was to study the long-term outcome in adulthood of patients with INS diagnosed during childhood. Method In this monocentric retrospective study, we included all adult patients (>18 years) admitted in our nephrology department between 2013 and 2019 with INS diagnosed during childhood. Patients who reached ESRD during childhood were excluded. Data regarding the outcome in adulthood were obtained through clinical database and medical charts. Results Eighty-two patients (M/F = 2/1) were included. Sixty-height patients had steroid-sensitive nephrotic syndrome (SSNS), including 52 with steroid-dependant nephrotic syndrome (SDNS). The other 14 patients had steroid-resistant nephrotic syndrome (SRNS). The median age at diagnosis was 3.9 years (1.2-16.5). The median number of relapses during childhood was 12 (0-52), 0.9/patient/year. 89% of patients received IS therapy in addition to S during childhood: median number of successive therapeutic lines was 3 (0-10) per child. Median follow-up during adulthood was 4.6 (0.1-25) years. 67% of patients experienced at least one relapse during adulthood, with a median number of relapses of 0.53 (0-3.7)/patient/year. Risk of relapse during adulthood was significantly associated with the total number of relapses during childhood (p=0.015) and with the number of relapses per year during childhood (p=0.007). 45% of patients received IS in addition to S during adulthood, mainly mycophenolate mofetil (23/82), calcineurin inhibitors (21/82) and rituximab (12/82). High blood pressure was observed in 22% of patients. At last follow-up, median eGFR was 90 (64-117) mL/min/1.73m in SSNS patients, 86 (57-126) mL/min/1.73m in SDNS patients and 70 (23-113) mL/min/1.73m in SRNS patients. Only 4/82 patients presented with eGFR lower than 60 mL/min/1.73m. Among them, 3 had SRNS. Only 1 thrombo-embolic event and 3 severe infections were reported. Bone densitometry was performed in 26 adult patients and osteopenia was found in 19 of them (73%). Conclusion The incidence of relapses in adulthood was relatively high in our study. However bias related to inclusion criteria could play a role. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent but major complications were rarely reported.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007–2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Background/Purpose Pathogenic antibody-secreting cells (ASC) are poorly characterized in human lupus nephritis (LN). Our objective was to compare the single cell molecular signature of ASC in kidney and urine from patients with active LN, either untreated or after immunosuppressive therapy failure. Methods ASC were identified by anti-CD138 staining on fixed renal biopsies from patients with active LN. We sorted single-ASC from fresh renal biopsies to perform gene expression profiling. ASC transcriptional program from urine of untreated LN patients was assessed at diagnosis and after a prospective follow up during induction therapy. Results Interstitial infiltrates of CD138+ ASC were found in untreated (N=15) and refractory patients (N=6). Single cell molecular signature of kidney ASC from untreated patients revealed that these cells were mostly plasmablasts and contrasted with ASC signature from patients with mycophenolate mofetil failure that expressed long-lived plasma cells genes and clustered with long-lived bone marrow ASC from healthy donors. A plasmablast signature was observed in urine ASC at diagnosis, similar to their kidney counterpart. The concentration of urine ASC from 22 untreated patients correlated with ISN/RPS classification, with higher concentration in class IV patients (p Conclusion These results suggest that plasmablasts infiltrate kidney of untreated LN patients, while kidney long-lived ASC may contribute to the failure of immunosuppressive therapy. Acknowledgement This work was funded by FOREUM.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Monogenic forms of Steroid-Resistant Nephrotic Syndrome (SRNS) have been widely characterized, but genetic screening paradigms preferentially address congenital, infantile onset, and familial cases. Our aim was to characterize the distribution of disease-causing gene mutations in adults with sporadic SRNS or focal segmental glomerulosclerosis (FSGS). We selected adult patients with non-syndromic, biopsy-proven FSGS or SRNS in the absence of known family history. Strict clinical criteria included lack of response to glucocorticoids and cyclosporine, and no recurrence after kidney transplantation. Mutations in SRNS genes were detected using a targeted gene panel. Sixteen of 135 tested participants (11.8%) carried pathogenic mutations in monogenic SRNS genes, and 14 others (10.4%) carried two APOL1 high-risk alleles. Autosomal recessive disease was diagnosed in 5 participants, autosomal dominant disease in 9, and X-linked disease in 2. Four participants carried a de novo heterozygous mutation. Among the 16 participants with identified mutations in monogenic SNRS genes, 7 (43.7%) had type IV collagen mutations. Mutations in monogenic SNRS genes were identified primarily in participants with proteinuria onset before 25 years of age, while the age at disease onset was variable in those with APOL1 high-risk genotype. Mean age at diagnosis was lower and renal survival was worse in participants with identified mutations in SNRS genes than in those without mutations. We found a significant rate of pathogenic mutations in adults with SRNS, with Type IV collagen mutations being the most frequent. These findings may have immediate impact on clinical practice.

Introduction L’HTAP associee au lupus est une complication rare mais severe. La place respective du traitement immunosuppresseur et du traitement vasodilatateur reste discutee: l’efficacite du traitement immunosuppresseur est inconstante et le traitement vasodilatateur est volontiers reserve aux patients les plus severes. Depuis les premieres publications sur le sujet, des scores pronostiques de l’HTAP ont ete developpes et la prise en charge therapeutique repose desormais sur leur evaluation. L’objectif de cette etude est d’evaluer l’impact respectif du traitement immunosuppresseur et du traitement specifique au cours de l’HTAP associee au lupus. Patients et methodes Trois groupes de patients issus de Registre francais d’hypertension arterielle pulmonaire et suivis a l’hopital Bicetre (France) ont ete analyses: des patients atteints de lupus traites par immunosuppresseurs seuls (LES-IS), des patients atteints de lupus traites par immunosuppresseurs et traitement specifique de l’HTAP (LES-IS + VD) et des patients avec HTAP idiopathique apparies au groupe LES-IS + VD sur l’âge, le sexe, le nombre de criteres ESC de faible risque selon la methode francaise, le type et le nombre de traitement specifique. Les donnees cliniques, hemodynamiques et 3 scores de risque (methode francaise selon le nombre de criteres ESC, methode COMPERA et score REVEAL) ont ete evalue a l’inclusion et a M6. Resultats Trente-trois patients avec HTAP associee a un lupus ont ete analyses: 17 avaient recu un traitement immunosuppresseur seul et 16 avaient recu un traitement immunosuppresseur et specifique de l’HTAP. Le groupe controle etait constitue de 16 patients atteints d’HTAP idiopathique. Les patients des groupes LES-IS et LES-IS + VD avaient tous recu du cyclophosphamide et des corticoides. Ils presentaient des anti-SSA/SSB dans 70 % et 56 % des cas et des anti-RNP dans 47 % et 43 % des cas respectivement. A l’exception de 3 patients, l’HTAP etait la seule manifestation systemique au moment du diagnostic de l’HTAP. A l’inclusion, les patients du groupe LES-IS + VD avaient une classe fonctionnelle NYHA plus elevee (p = 0,04), un index cardiaque plus bas (2,38 [2,07–2,61] versus 3,36 [2,63–3,89] L/min/m2 ; p Discussion Bien qu’ils soient plus graves, les patients traites par immunosuppresseur et traitement specifique de l’HTAP presentent une amelioration significative des parametres cliniques, hemodynamiques et des scores de risque alors que ces parametres restent stables chez les patients traite par IS seul. Cela remet en question l’efficacite du traitement immunosuppresseur et soutient une utilisation systematique du traitement specifique de l’HTAP dans la prise en charge des patients lupiques. La reponse therapeutique de certains patients du groupe LES-IS et l’amelioration plus marquee en donnees individuelles des patients du groupe LES-IS + VD compares aux patients HTAPi sont deux elements distincts qui suggerent neanmoins un benefice du traitement immunosuppresseur. Conclusion Le traitement immunosuppresseur seul ne permet pas d’ameliorer significativement les scores pronostiques des patients traites pour HTAP associee a un lupus. L’amelioration hemodynamique et des scores pronostiques repose essentiellement sur le traitement specifique. L’impact reel du traitement immunosuppresseur seul semble persister mais reste a evaluer. Des etudes prospectives, difficiles a conduire du fait de la rarete de la maladie, seraient necessaires pour mieux repondre a cette question.

Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models. Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10–12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28–10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29–2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00–3.20; P = 0.049). Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first‐line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.

Background: Pathogenic antibody secreting cells (ASC) have been identified in the kidney of SLE-prone mice, but are poorly characterized in human lupus nephritis (LN). We hypothesized that long-lived plasma cells may contribute to the failure of immunosuppressive therapy in refractory patients. Objectives: To characterize and compare the single cell molecular signature of ASC in kidney and urine from patients with active LN, either untreated or after immunosuppressive therapy failure. Methods: We included patients with biopsy proven active LN from 4 centers and meeting the ACR revised classification criteria for SLE diagnosis. Renal biopsies were scored according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, and stained with anti-CD138 to visualize ASC. ASC were single cell sorted as CD3-/CD14-/CD16-/CD27high/CD38high cells. Single-cell gene expression profiling was performed by multiplex RT-PCR using Fluidigm Dynamic Arrays. We used a set of genes derived from a previous transcriptomic analysis of human splenic and bone marrow ASC to distinguish the process of ASC maturation from plasmablast (PB) to long-lived PC. We also studied ASC transcriptional program from urine of untreated LN patients at diagnosis and after 3 and 6 months of a prospective follow up during induction therapy (Plasmo-Lup study). Results: Immunohistochemistry stainings on kidney biopsies from both untreated (N=15) and refractory patients (N=6) showed infiltrates of CD138+ ASC mainly located in the interstitium, particularly in untreated patients. Single cell molecular signature of kidney ASC from 3 untreated patients with class IV LN revealed that these cells were mostly PB expressing multiple genes linked with cell division, and PC without long-lived genes expression. This contrasted with ASC signature from 3 patients with active LN and mycophenolate mofetil (MMF) failure that expressed long-lived PC genes and no proliferative genes. Primary component analysis of 170 single-cells showed clustering of ASC from MMF treated patients with long-lived bone marrow PC from healthy donors that were distinct from PB/PC from untreated patients (Figure 1). A PB signature was observed in urine ASC at diagnosis, similar to their kidney counterpart. The concentration of ASC in urine in 22 untreated patients correlated with ISN/RPS classification, with higher concentration in class IV patients (p Conclusion: These results suggest that PB infiltrate kidney of untreated LN patients, and that kidney long-lived PC may contribute to the failure of immunosuppressive therapy. Acknowledgement: This work was supported by Foreum Disclosure of Interests: None declared

Little is known about the long-term progression of adult nephropathic cystinosis patients. Our objective was to study central nervous system complications in cystinosis patients in the era of early cysteamine treatment, using advanced neuroimaging techniques. Neurological examination and multimodal brain 3 Tesla MRI were performed in 21 adult cystinosis patients, including 18 infantile cystinosis patients, 20 controls matched for age and renal function, and 12 healthy controls. Differences in gray matter volume and rest cerebral blood flow (CBF) using arterial spin labeling sequence were investigated using whole-brain voxel-based approach. Median age was 33.8 years (18.7-65.8). Seven patients (38.9%) presented with at least one central nervous system clinical abnormality: two (11.1%) with seizures, three (16.7%) with memory defects, five (27.8%) with cognitive defect, and one (5.5%) with stroke-like episode. These patients had a worse compliance to treatment (compliance score 2 vs 1, P = .03) and received a lower median cysteamine dose (0.9 g/day vs 2.1 g/day, P = .02). Among patients with infantile cystinosis, 13 (72.2%) showed cortical atrophy, which was absent in controls, but it was not correlated with symptoms. Cystinosis patients showed a significant gray matter decrease in the middle frontal gyrus compared with healthy controls and a significant negative correlation between the cystine blood level and rest CBF was observed in the right superior frontal gyrus, a region associated with executive function. Compliance to cysteamine treatment is a major concern in these adult patients and could have an impact on the development of neurological and cognitive complications.

Background A therapeutic strategy based on complement blockade by eculizumab is widely used to treat atypical haemolytic uraemic syndrome (aHUS). Recent data are available on the administration of eculizumab during pregnancy in patients treated for paroxysmal nocturnal haemoglobinuria but there are very few data for aHUS patients. Methods We analysed the use of eculizumab for the treatment of aHUS during five pregnancies in three patients and studied an additional pregnancy without eculizumab. Obstetrical data and maternal and foetal complications during pregnancy, at delivery, and during the post-partum period were recorded. Results The mean age at pregnancy was 28.5 (range 25-33) years. The mean serum creatinine before pregnancy was 189 (range 130-300) µmol/L and the mean eGFR was 32 (range 18-45) mL/min/1.73 m2. One patient who stopped eculizumab 3 weeks after conception had a termination due to a relapse of HUS at 12 weeks of gestation (WG) during a first pregnancy and an intrauterine death at 24 WG despite continuous eculizumab treatment during a second pregnancy. In the other four pregnancies, treatment stabilized clinical and laboratory markers until 29-34 WG, but did not prevent hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome in one patient or pre-eclampsia in two other patients. All babies were born preterm and two presented with growth retardation. The mean body weight was 1632.5 (range 1070-2500) g. The dose of eculizumab had to be increased during all pregnancies due to incomplete complement blockade. Conclusions Eculizumab therapy during pregnancy displayed no overt safety issues but did not appear to prevent HELLP syndrome or pre-eclampsia in these high-risk chronic kidney disease patients.

Genetic investigations were performed in three brothers from a consanguineous union, the two oldest diagnosed with rod-cone dystrophy (RCD), the youngest with early-onset cone-rod dystrophy and the two youngest with nephrotic-range proteinuria. Targeted next-generation sequencing did not identify homozygous pathogenic variant in the oldest brother. Whole exome sequencing (WES) applied to the family identified compound heterozygous variants in CC2D2A (c.2774G>C p.(Arg925Pro); c.4730_4731delinsTGTATA p.(Ala1577Valfs*5)) in the three brothers with a homozygous deletion in CNGA3 (c.1235_1236del p.(Glu412Valfs*6)) in the youngest correcting his diagnosis to achromatopsia plus RCD. None of the three subjects had cerebral abnormalities or learning disabilities inconsistent with Meckel-Gruber and Joubert syndromes, usually associated with CC2D2A mutations. Interestingly, an African woman with RCD shared the CC2D2A missense variant (c.2774G>C p.(Arg925Pro); with c.3182+355_3825del p.(?)). The two youngest also carried compound heterozygous variants in CUBN (c.7906C>T rs137998687 p.(Arg2636*); c.10344C>G p.(Cys3448Trp)) that may explain their nephrotic-range proteinuria. Our study identifies for the first time CC2D2A mutations in isolated RCD and underlines the power of WES to decipher complex phenotypes.

Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p

Introduction Le syndrome nephrotique idiopathique cortico-dependant (SNICD) apparu dans l’enfance constitue une maladie chronique faite de phases de poussees et de remissions. Toutefois, son impact global (insertion socio-professionnelle, qualite de vie, transition) a long terme est mal connu. Methodes Les donnees de 59 adultes (20 services de nephrologie) suivis pour un SNICD avec 1ere poussee avant 16 ans ont ete recueillies sur dossier medical et par auto-questionnaire entre decembre 2016 et avril 2017. L’auto-questionnaire GEDEPAC2 comporte 109 items, explorant 11 domaines du bien-etre (education, emploi, logement, securite materielle, liens sociaux, engagement civique, loisirs, environnement, sante physique/conduites risque, qualite de vie, vie sexuelle) et inclue 3 questionnaires (qualite de vie SF-12 ; Treatment Burden questionnaire ; fatigue MFI-20). Analyse descriptive et comparative a la population generale (INSEE) par ratios standardises d’incidence (RSI) ajustes sur âge, sexe et periode. Resultats obtenus ou attendus Parmi les 59 participants (âge median = 32 ans [Q1 = 26 ;Q3 = 37] ; hommes = 80 %), 34 % avaient eu moins de 10 rechutes, 26 % plus de 20 rechutes ; 84 % etaient en remission complete au remplissage du questionnaire. La vie en couple etait aussi frequente qu’attendue (RSI = 1,48 ; IC95 % = [0,89 ;2,07]). 56,9 % avaient un diplome superieur contre 16 % attendu (RSI = 3,52 ; IC95 % = [2,24 ;4,81]), traduisant un possible surinvestissement scolaire chez ces enfants. Le chomage etait plus frequent (21 % ; RSI = 2,78 ; IC95 % = [1,21 ;4,36]). Du fait de la maladie, 50 % avait renonce au sport et 76 % disaient avoir subi des discriminations, particulierement a l’ecole. La qualite de vie etait alteree au niveau des scores composites SF-12 physique (moyenne = 50 ± 10) et mental (moyenne = 41 ± 10). La transition pediatrie/services d’adultes etait souvent bien vecue (sentiment de continuite pour 74 %). Mais la majorite des patients deplorent une preparation insuffisante(65 %) ( Fig. 1 ). Conclusion Cette etude apporte un nouvel eclairage sur le bien-etre des adultes avec SNICD a debut pediatrique. Si leur insertion sociale parait satisfaisante d’apres certains indicateurs, ces personnes rencontrent au quotidien des difficultes professionnelles, des discriminations ou encore une fatigue intense.

Resume L’etude des sous-classes des immunoglobulines G composant les depots immuns dans la glomerulonephrite extramembraneuse (GEM) permet d’orienter le diagnostic etiologique. Les depots d’IgG4 sont le plus souvent vus dans les formes dites primitives, liees a la presence d’auto-anticorps (anticorps dirige contre le recepteur de la phospholipase A2 [PLA2R] dans la majorite des cas) et ils sont polytypiques avec chaines legeres kappa et lambda. Dans les formes dites secondaires, les depots comportent plutot de l’IgG1, IgG2 et IgG3. Nous rapportons le cas d’une patiente âgee de 52 ans, dont la biopsie renale pour proteinurie glomerulaire met en evidence une GEM a depots monotypiques d’IgG4 kappa sans anticorps anti-PLA2R.

Resume Propos L’objectif de ce travail etait de proposer des recommandations relatives aux modalites de depistage et de prise en charge des facteurs de risque cardiovasculaire au cours du lupus systemique. Methodes Trente-neuf experts internistes, rhumatologues ou nephrologues francais, membres du reseau des centres de reference et de competence du lupus systemique ont pris part a un vote visant a retenir ou non des recommandations preparees par un groupe de travail a partir d’une revue de la litterature. Resultats Les experts ont souligne que les facteurs de risque cardiovasculaires modifiables doivent etre recherches au moins annuellement au cours du lupus systemique. La prescription d’une statine en prevention primaire depend du taux de LDL-cholesterol et du nombre de facteurs de risque cardiovasculaires, en considerant le lupus systemique comme un facteur de risque cardiovasculaire supplementaire. En prevention secondaire, les experts s’accordent a proposer une cible de LDL-cholesterol Conclusions Ces recommandations vont permettre d’ameliorer et d’homogeneiser la pratique des differents medecins francais impliques dans la prise en charge du lupus systemique. L’actualisation de ces recommandations pourra etre ulterieurement envisagee, en fonction des nouvelles donnees publiees.

International audience; Monoclonal gammopathy of renal significance (MGRS) regroups renal disorders caused by a monoclonal immunoglobulin without overt hematological malignancy. MGRS includes tubular disorders, glomerular disorders with organized deposits, and glomerular disorders with non-organized deposits, such as proliferative glomerulonephritis with monoclonal IgG deposits. Since glomerular involvement related to monotypic IgA deposits is poorly described we performed retrospective analysis and defined clinico-biological characteristics, renal pathology, and outcome in~19 referred patients. This analysis allowed distinction between 2 types of glomerulopathies, α-heavy chain deposition disease (5 patients) and glomerulonephritis with~monotypic IgA deposits (14 patients) suggestive of IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits in 12 cases. Clinicopathologic characteristics of α-heavy chain deposition disease resemble those of the γ-heavy chain disease, except for a higher frequency of extra-capillary proliferation and extra-renal involvement. IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits should be differentiated from diseases with polytypic IgA deposits, given distinct clinical, histological, and pathophysiological features. Similarly to IgG-proliferative glomerulonephritis with monoclonal immunoglobulin deposits, overt hematological malignancy was infrequent, but sensitive serum and bone marrow studies revealed a subtle plasma cell proliferation in most patients with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Anti-myeloma agents appeared to favorably influence renal prognosis. Thus, potential progression towards symptomatic IgA multiple myeloma suggests that careful hematological follow-up is mandatory. This series expands the spectrum of renal disease in MGRS.

International audience; Objective. Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment. Methods. We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American–European Consensus Group criteria or enlarged American–European Consensus Group criteria, and with biopsy-proven renal involvement. Results. A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of

Le syndrome hemolytique et uremique (SHU) est defini par la triade anemie hemolytique mecanique intravasculaire, thrombopenie et insuffisance renale aigue. La plupart des SHU non lies a une infection par Escherichia coli produisant une shigatoxine se presentent comme une maladie primitive appelee SHU atypique, en rapport le plus souvent avec une deregulation du systeme du complement. Avant l’ere du traitement specifique, le pronostic etait severe puisque 2 a 10 % des patients decedaient au cours de la premiere poussee et qu’un tiers evoluait vers l’insuffisance renale terminale. La comprehension du role du complement a ouvert la voie a une nouvelle therapeutique, l’eculizumab, une immunoglobuline G recombinante monoclonale humanisee anti-C5 qui bloque le clivage du C5. Il a prouve son efficacite avec 85 % de reponse, que les patients soient plasmaresistants ou plasmadependants. Il permet un meilleur controle de la maladie renale que la plasmatherapie. L’eculizumab est desormais recommande en premiere intention chez l’enfant et des que les principales causes secondaires de SHU ont ete eliminees chez l’adulte. Dans tous les cas, l’utilisation de l’eculizumab est recommandee en cas de resistance a trois a cinq echanges plasmatiques quotidiens. La normalisation du chiffre de plaquettes ne doit pas etre le seul critere de jugement de l’efficacite de la plasmatherapie. Elle doit etre consideree comme inefficace s’il persiste une thrombopenie, mais aussi si la creatininemie ne diminue pas et/ou si des stigmates d’hemolyse persistent.

The Kidney Disease Improving Global Outcomes (KDIGO)-2012 on the treatment of anemia emit suggestions (which differ from recommendations) based on a scientific evidence of low level. The first rule is no harm; physicians must take into account the profile of the patient and its associated morbidities and remember on the potential risks to begin a treatment by erythropoiesis stimulating agents (ESA) (thrombosis of arteriovenous fistula, hypertension, stroke). All correctable causes of anemia other than erythropoietin deficiency should be actively sought. It is necessary to individualize the treatment by ESA and assess the clinical improvement expected. The ESA will be used in the following way: initiate at 10 g/dL of hemoglobin level with the aim of 11.5 g/dL, without exceeding 13 g/dL. In case of ESA resistance, it seems suitable to assess the risks and benefits of ESA versus blood transfusion. The ERBP-2013 have endorsed the KDIGO-2012 except the proposals dealing with the treatment by IV iron. The use of intravenous iron must be more cautious in the future taking into account the results of a recent French study published in the American Journal of Medicine showing the high frequency of iron overload at quantitative hepatic MRI among haemodialysis patients receiving iron IV following the current guidelines. It is appropriate to use oral iron in first intention as recommended by the ANSM (French Drug Agency) in a recent information note and respect the dosage regimen of the label. The realization of a quantitative hepatic MRI to evaluate iron overload and monitor the treatment by iron IV must also be considered on a case by case basis.