Background. The anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden and prevalent microscopic polyangiitis. Methods. We retrospectively studied a cohort of 192 patients over 65 years of age [median (interquartile range) age: 73 (68-78) years], including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres in northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event. Results. The median serum creatinine concentration at diagnosis was 300 (202-502) mu mol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%) and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% (interquartile range 7.6-20.0) in the medium-risk group and 44.0% (29.0-58.0) in the high-risk group (P < .001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 (0.58-0.74) for the prediction of ESKD at 12 months; this rose to 0.86 (0.80-0.90) when dialysis status at diagnosis was included. Conclusion. The ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement-especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the predictive performance of the ARRS.

Background The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC. Methods We conducted a retrospective, multicentre study comparing PEXIVAS redGC with standGC in patients with AAV. The primary composite outcome was the occurrence of death, ESKD, AAV progression before remission or relapse within the 12 months following induction. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Factors associated with the occurrence of the primary outcome were estimated. Results A total of 234 patients were included. The primary composite outcome occurred in 42/126 (33%) patients with redGC versus 20/108 (19%) with standGC. In unweighted multivariable analysis and in weighted analysis, redGC was independently associated with the primary outcome but not with death or ESKD. Among redGC-treated patients, those with serum creatinine>300 µmol/L were more likely to achieve the primary outcome. RTX-treated patients who received redGC were more likely to experience death or ESKD and to achieve the primary outcome. Conclusion In this study of patients with AAV primarily treated with RTX, redGC was associated with an increased risk of the primary outcome consisting of death, ESKD, AAV progression before remission or relapse.

OBJECTIVES:To describe the characteristics, treatment and outcome of isolated ANCA-associated scleritis at diagnosis compared with idiopathic scleritis with negative ANCA tests. METHODS:This retrospective multicentre case-control study was performed within the French Vasculitis Study Group (FVSG) network and in three French tertiary ophthalmologic centres. Data from patients with scleritis without any systemic manifestation and with positive ANCA results were compared with those of a control group of patients with idiopathic scleritis with negative ANCA tests. RESULTS:A total of 120 patients, including 38 patients with ANCA-associated scleritis and 82 control patients, diagnosed between January 2007 and April 2022 were included. The median follow-up was 28 months (IQR 10-60). The median age at diagnosis was 48 years (IQR 33-60) and 75% were females. Scleromalacia was more frequent in ANCA-positive patients (P = 0.027) and 54% had associated ophthalmologic manifestations, without significant differences. ANCA-associated scleritis more frequently required systemic medications, including glucocorticoids (76% vs 34%; P < 0.001), and rituximab (P = 0.03) and had a lower remission rate after the first- and second-line treatment. Systemic ANCA-associated vasculitis (AAV) occurred in 30.7% of patients with PR3- or MPO-ANCA, after a median interval of 30 months (IQR 16.3-44). Increased CRP >5 mg/l at diagnosis was the only significant risk factor of progression to systemic AAV [adjusted hazard ratio 5.85 (95% CI 1.10, 31.01), P = 0.038]. CONCLUSION:Isolated ANCA-associated scleritis is mostly anterior scleritis with a higher risk of scleromalacia than ANCA-negative idiopathic scleritis and is more often difficult to treat. One-third of patients with PR3- or MPO-ANCA scleritis progressed to systemic AAV.

Background IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. Methods We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR <= 30 ml/ min per 1.73 m(2) at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. Results We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m(2) in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR <= 30 ml/min per 1.73 m(2). Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level >= 5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. Conclusions IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (>= 5 g/L) had more severe kidney disease.

Objective. - To evaluate rituximab (RTX) resistance at 3 months (M3) of induction therapy in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV).Methods. - Multicentre French retrospective study conducted between 2010 and 2020 including patients with newly diagnosed or relapsing AAV (granulomatosis with polyangiitis or microscopic polyangiitis) having received induction therapy with RTX. Primary endpoint was the presence of RTX resistance at 3 months (M3) defined as uncontrolled disease (worsening feature on the BVAS/WG 1 month after RTX induction) or disease flare (increase in BVAS/WG of & GE; 1 point before M3).Results. - Out of 121 patients included, we analysed 116 patients. Fourteen patients (12%) had RTX resistance at M3 with no difference in baseline demographics, vasculitis type, ANCA type, disease status or organ involvement. Patients with RTX resistance at M3 had a greater proportion of localized disease (43% vs. 18%, P < 0.05) and were less often treated by initial methylprednisolone (MP) pulse (21% vs. 58%, P < 0.01). Out of the 14 patients with RTX resistance, seven received additional immunosuppressive therapy. All patients were in remission at 6 months. Compared to responders, patients with RTX resistance at M3 were less often treated with prophylactic trimethoprim-sulfamethoxazole (57% vs. 85%, P < 0.05). Twenty-four patients died during follow-up, one-third of them from infections and half of them from SARS-CoV-2.Conclusion. - Twelve percent of patients had RTX resistance at M3. These patients more often had localized form of the disease and were less treated by initial MP pulse and by prophylactic trimethoprim-sulfamethoxazole.& COPY; 2023 L'Auteur(s). Publie & PRIME; par Elsevier Masson SAS au nom de Socie & PRIME;te & PRIME; franc, aise de rhumatologie. Cet article est publie & PRIME; en Open Access sous licence CC BY-NC-ND (http://creativecommons.org/licenses/bync-nd/4.0/).

Introduction: Complement activation emerged as a key actor of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Whether serum levels of C3 (sC3) or C3 kidney deposition may help to refine the prognosis of AAV remains elusive.Methods: Retrospective multicentric study that included 154 patients with a first flare of AAV and sC3 (n = 143) or C3 kidney staining (n = 95) available at diagnosis. Clinical presentations, kidney pathology, and survival of patients with normal or low sC3 were compared using univariate analyses, Kaplan-Maier curves with log-rank comparison, or multivariate Cox' model, as appropriate.Results: 20 patients (14 %) had low sC3. sC3 (as bivariate low/normal or as a continuous variable) was associated with 5-year mortality but not with kidney survival. C3 kidney deposition (C3+) was identified in 23 patients who were characterized by more frequent chronic hypertension and lower eGFR at presentation (p = 0.04). C3+ correlated with IgG, IgM, C1q deposition (p = 0.07, p < 0.0001 and p = 0.003, respectively). Chronicity and activity scores were similar in C3+ and C3-patients. Among C3+ patients, those with C3 deposition >= 2+ had lower eGFR at presentation (p = 0.006) and were more frequently classified as sclerotic using the Berden classification (p = 0.04) and as 'high risk' using the Brix score (p = 0.03). However, eGFR improvement following induction regimen was similar between C3+ and C3-patients, and kidney survival at 5 years was similar.Conclusions: Correlation of sC3 with mortality confirms mechanistic links between complement pathways and AAV, but the lack of clear predictive sC3 cut-off and the similar kidney outcome irrespective of C3 deposition precludes their use as biomarkers of AAV outcomes and response to treatment.

BACKGROUND:The landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking.METHODS:This retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed.RESULTS:196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12-3.08), gastrointestinal involvement (1.95; 95% CI1.09-3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24-3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23-6.37), necrotic purpura (HR 4.16; 95%CI 1.62-10.70), acute kidney injury (HR 4.89; 95% 1.71-13.99) and secondary PAN (HR 2.98; 95%CI 1.29-6.85) were independently associated with mortality.CONCLUSION:Landscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.

Background Little is known about antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in older patients. We aim to study relapse risk of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in patients diagnosed after 75 years and compare it with those of patients aged 65-75 years. Methods Data from AAV patients aged >= 65 years were extracted from the French Vasculitis Study Group (FVSG) database and from a call for observation to FVSG members. Cox and Fine-Gray models were used to assess relapse risk, taking death into account either as a censoring or a competing event, respectively. Results The analysis included 219 patients aged >= 75 years (median 79) and 80 patients aged 65-75 years (median 70), of those 155 had GPA (52%), 136 MPA (45%), with 95 (32%) anti-proteinase 3 positivity and 179 (61%) anti-myeloperoxidase. Patients aged >= 75 years had a lower relapse risk in multivariate analysis (cause-specific hazards ratio [CSHR] 0.54, 95% CI [0.33-0.89], p = 0.016, Cox model; subdistribution hazard ratio [SHR] 0.46, 95% CI [0.29-0.74], p = 0.001, Fine-Gray model) after taking into account vasculitis type. Patients aged >= 75 years had a lower probability of being treated for remission maintenance with a combination of glucocorticoids and immunosuppressants (vs. glucocorticoids alone, HR 0.28, 95% CI [0.11-0.68], p = 0.005) after adjusting to Five Factor Score, although relapse-free survival was significantly longer when receiving such combination (CSHR 0.40, 95% [CI 0.24-0.67], p < 0.001). Conclusions AAV patients >= 75 years have a lower relapse risk than patients aged 65-75 years despite a lower probability of having received maintenance therapy with a combination of glucocorticoids and immunosuppressants, but they still benefit from such treatment regimen.

Significance Statement Findings of the international prospective multicenter PEXIVAS trial challenge the role of PLEX in AAV. We conducted a retrospective study of 425 patients: 188 with AAV and renal failure treated with PLEX and 237 not treated. A score to identify patients who would benefit from PLEX was developed. With kidney biopsy data, scores more than seven achieved sensitivity and specificity of 83.1% and 96.0%, respectively, for recommending PLEX. The average effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. Patients in the PLEX-recommended group had microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score. These findings, which require independent validation, could provide guidance in selecting patients with AAV who will benefit from PLEX. Background Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. Methods We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). Results No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (−15.9%; 95% CI, −29.4 to −2.5) compared with the PLEX not recommended group (−4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. Conclusions PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.

IMPORTANCE Older patients are underrepresented in studies of rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Little is known about outcomes and adverse events associated with the use of rituximab therapy among patients 75 years and older with ANCA-associated vasculitis. OBJECTIVE To examine outcomes and adverse events associated with the use of rituximab therapy in patients 75 years and older with ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study involved 93 patients 75 years and older with ANCA-associated vasculitis from 36 university and nonuniversity hospitals in France. Data were obtained from the French Vasculitis Study Group database between January 1, 2000, and July 1, 2018, and a call for observation sent to French Vasculitis Study Group members on June 6, 2019. Data analysis was performed from November 15 to December 31, 2021. Inclusion criteria included a diagnosis of GPA orMPA according to European Medicines Agency classification criteria and receipt of treatment with rituximab after age 75 years. Patients were excluded if they were missing relevant clinical or biological data. Data on race and ethnicity were not reported because inclusion of this information was not authorized by the ethics committee. EXPOSURE At least 1 infusion of rituximab as induction or maintenance therapy. MAIN OUTCOMES AND MEASURES Occurrence of remission, relapse, drug discontinuation, death, and serious infections (including types of serious infections). RESULTS Of 238 patients screened, 93 were included (median [IQR] age, 79.4 [76.7-83.1] years; 51 women [54.8%]); 52 patients (55.9%) had a diagnosis of GPA, and 41 (44.1%) had a diagnosis of MPA. Thirty patients (32.3%) received rituximab as induction therapy in combination with high-dose glucocorticoid regimens, 27 (29.0%) received rituximab as maintenance therapy, and 36 (38.7%) received rituximab as both induction and maintenance therapy. The median (IQR) follow-up was 2.3 (1.1-4.0) years. Among 66 patients who received rituximab as induction therapy, 57 (86.4%) achieved remission, and 2 (3.0%) experienced relapses. The incidence of serious infection was significantly higher when rituximab was used as induction therapy vs maintenance therapy (46.6 [95% CI, 24.879.7] per 100 patient-years vs 8.4 [95% CI, 3.8-15.9] per 100 patient-years; P =.004). Most infections (12 of 22 [54.5%]) were gram-negative bacterial infections. The incidence of deathwas 19.7 (95% CI, 7.2-42.9) per 100 patient-years among those who received rituximab as induction therapy and 5.3 (95% CI, 1.9-11.6) per 100 patient-years among those who received rituximab as maintenance therapy. CONCLUSIONS AND RELEVANCE In this cohort study, rituximab therapy was associated with achievement and maintenance of remission in most patients 75 years and older with ANCA-associated vasculitis. The incidence of serious infections and death was high when rituximab was used as induction therapy in combination with high-dose glucocorticoid regimens but not when rituximab was used as maintenance therapy. Efforts might focus on reducing serious infections during the first months of therapy.

We assessed the tubular reabsorption of phosphate (TRP) and maximal renal threshold for phosphate reabsorption to glomerular filtration rate (TmPi/GFR) and their determinants in 64 stages 2-4 chronic kidney disease (CKD) patients in order to define the early changes in phosphate metabolism in CKD. In multivariable analysis, TmPi/GFR correlates were estimated GFR (eGFR), intact parathyroid hormone (iPTH), and hemoglobin (R2 = 0.417), while TRP correlates were eGFR, iPTH, 24-h phosphaturia, and calcitriol (R2 = 0.72). This suggests that TmPi/GFR and TRP, respectively, assess hemoglobin-phosphate and bowel-kidney phosphate regulation axis. Iron supplementation based on TmPi/GFR or earlier phosphate restriction based on TRP should be investigated in view of modifying clinical outcomes in CKD.

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 <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study. CONCLUSION.:Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.

suppressed the increase to 29.3 6 20.5 mV (P=0.012). The blood cell count did not change significantly. For the biochemistry data, the ferritin level decreased from 91.9 6 77.0 ng/mL to 63.0 6 46.7 ( P = 0.035), while all other investigated parameters did not show any significant changes. The VAS score for fatigue after hemodialysis also decreased from 2.9 6 2.7 to 2.0 6 2.5 ( P = 0.015). CONCLUSIONS: A dialysate reduction system in which hydrogen gas is dissolved in an acid concentrate enabled a reduction in the ORP of the dialysate. In dialysis treatment using this device, a significant decrease in ORP of blood was also observed. The ferritin level, which is an indicator of chronic inflammation, and the VAS score for fatigue were also reduced. This system might be useful for reducing OS in hemodialysis patients. optical sensor on the arterial line allow to monitoring SO2 throughout the session. The signal was acquired with a frequency of 1 sample per 5 seconds and the variability can be calculated with the standard deviation over a 5 minutes long window. Blood pressure, pulse rate, ultra filtration, every symptomatic IDH and their occurence time were collected. We used a Relative Operating Characteristic analysis to determine diagnostic performances of SO2 variability to predict IDH, expressed by area under curve (AUC), sensitivity and specificity. RESULTS: Among the 91 dialysis sessions of the study, an IDH occurred in 13,4% of case. The blood flow was 350 +/- 21 mL/minutes, the session duration was 260 +/- 27 minutes and the ultrafitration rate was 2,72 +/- 0,78 liters. The analyse show that the mean SO2 was comparable between hypotension and no hypotension sessions (95,6 % versus 96,1 % ; p = 0,318). However, SO2 fall was more important in sessions with IDH (85,7% versus 90,3% ; p = 0,001) such as the maximal peak of SO2 variability equal to 3,14 +/- 1,09 (1,37 - 4,96) against 2,05 +/- 1,18 (0,58 - 5,58) (p = 0,001). AUC curve defines a threshold of SO2 variability equal to 2.094 to have the most predictive performances of IDH (AUC 0,778). The sensitivity was 92,3%, the specificitywas 65,4%, and the predictive positive value was 98,1%. The occurrence time of IDH after exceed the threshold was 57 +/- 28 minutes. The analyse shows a better specificity of the system with a specific threshold for each patient that can reach 93,8%. Instead, the performance appears less effective in chronic hypotension patients. CONCLUSIONS: Variability of SO2 during hemodialysis sessions seems to be a good tool to predict IDH. The best education of this study is that the system must to be individualized for each patient with a specific threshold of SO2 variability. In the future, we can imagine taking advantage of the time between exceeding the threshold and hypotension to implement manoeuvres to ovoid the occurrence of IDH. they