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BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) is rare among children but leads to kidney failure (KF) in almost 30% of cases with renal involvement [1]. Kidney transplantation (KT) is the treatment of choice in adults with AAV and KF, while data among children are limited to small case series [2, 3]. We report the outcomes of KT in a multicentre cohort of patients with childhood-onset AAV. METHOD Patients with AAV diagnosed before the age of 18 years who had undergone KT were identified at one Canadian and 20 European centres. We analysed patient and graft survival and the rates of rejection, AAV relapse and infections. Eighteen patients from this cohort had already been reported in previous articles [1, 2]; their follow-up was extended and further relevant data were retrieved. RESULTS We included 55 patients, of whom 38 (69%) had microscopic polyangiitis (MPA) and 17 (31%) granulomatosis with polyangiitis (GPA). Their median age at diagnosis and transplantation was, respectively, 12 (interquartile range, IQR 9–14) and 14 (IQR 12–16) years (Table 1). Living donor transplantation was performed in 20 cases (36%) and deceased donor transplantation in 35 (64%). At the time of transplantation, all patients were in clinical remission and ANCA was positive in 14/54 (26%). As immunosuppressive therapy, 46 patients (84%) received glucocorticoids, tacrolimus and either mycophenolate mofetil or azathioprine. The median follow-up after transplantation was 54 months (IQR 21–91). Acute rejection was reported in 22 patients (40%), 12 of whom experienced it during the first post-transplant year, while chronic rejection was established in two (4%). AAV relapsed in five cases (9%) and involved the graft in 4/5. Positive ANCA at transplantation was significantly associated with relapse (29% versus 2%; P = 0.02). Infections occurred in 34 patients (62%), and were mainly bacterial infections of the urinary tract or viral infections due to CMV (8/34), EBV (5/34) and BK virus (4/34). No patient developed malignancy. At last visit, all patients were alive and 48 (87%) had a functioning graft. Graft function impairment (eGFR CONCLUSION KT in childhood-onset AAV has a relatively good graft and patient survival, while the rate of complications and the risk of vasculitis relapse appear low. Positive ANCA at the time of transplantation may be a risk factor for both AAV relapse and graft function impairment.

Background and Aims Renal involvement in ANCA-associated vasculitis (AAV) impacts significantly on patients’ prognosis. The role of different induction regimens on remission rates and long-term renal outcomes according to renal histological characteristics has not been explored yet. Method AAV patients with biopsy-proven renal involvement were collected retrospectively from eleven centers and stratified according to the induction regimen employed: Rituximab (RTX), Cyclophosphamide (CYC) or both (RTX-CYC). Kidney biopsies were classified according to the Berden and Brix classifications. Renal remission rate was assessed 6 months after the induction regimen and defined as a renal Birmingham Vasculitis Activity Score (BVAS) of 0. Among patients who achieved remission at 6 months, renal relapse was defined as a renal-BVAS>0 associated with an increase in immunosuppressive treatment. ESRD was defined as an eGFR Results 323 patients were identified and followed-up for a median time of 36 months (IQR 18-72). The cohort included 38% patients with GPA and 62% with MPA, 53% patients were MPO-ANCA and 41% PR3-ANCA positive. The median baseline eGFR in the overall cohort was 19 ml/min/1,73m2 (IQR 12- 34). 58% of patients were treated with CYC, 24% with RTX-CYC and 18% with RTX. According to the Berden classification, 24% biopsies were classified as Focal, 31% as Crescentic, 33% as Mixed and 12% as Sclerotic. The Brix score was assessable in 270/323 (84%) patients: 17%, 52% and 31% were respectively in the Low, Medium and High-risk class. The overall renal remission at 6 months was 90%; according to the Berden classification, 94% patients achieved remission in the Focal, 88% in the Crescentic, 91% in the Mixed and 86% in the Sclerotic class. According to the Brix risk score, 88% patients achieved remission in the High risk, 91% in the Medium and 96% in the Low-risk class. According to induction regimen employed, 91%, 90% and 90% patients achieved remission in the RTX, CYC and RTX plus CYC group respectively. In a logistic regression model adjusted for sex, age, ANCA type, AAV diagnosis, creatinine and proteinuria at onset, the induction regimen employed was not predictive of renal remission at 6 months, neither in Berden Focal plus Crescentic and Mixed plus Sclerotic classes, nor in Brix High and Low plus Medium risk classes. Of the 185 patients with at least 6 months of follow-up available after remission, 25% experienced a renal relapse. In a Cox regression model adjusted for sex, age, ANCA type, AAV diagnosis, creatinine and proteinuria at onset, the induction regimen or histological score were not predictive of renal relapse. In the unadjusted survival analysis with the Kaplan-Maier curve, patients in the Crescentic group treated with RTX had a shorter ESRD-free survival compared to the CYC group (p=0.033) and the RTX-CYC group (p=0.044); figure 1: This was confirmed also with a Cox regression analysis adjusted for sex, age, ANCA type, AAV diagnosis, creatinine and proteinuria when comparing the RTX group with the CYC one (HR 8.30 [95% CI 1.64 to 42.01], p=0.011); figure 2: While the eGFR changes over time in the Focal plus Crescentic and Mixed plus Sclerotic classes showed a similar trend between treatment groups, in the Crescentic class the median eGFR values in the RTX group tended to be lower compared to the CYC and the RTX-CYC ones; figure 3: The rate of severe infections in the RTX, CYC and RTX-CYC group was respectively 6.3, 8.5 and 8.8 per 100 patient-years during the first 12 months. Conclusion in a retrospective multicenter survey, response rates and relapse risk after different induction regimens in AAV patients with renal involvement were comparable in the overall cohort and in the different histopathological subgroups. Although in a small subset of patients, the ESRD-free survival in the Crescentic class was shorter in the RTX group compared to the CYC one.

Background and Aims Glucocorticoids (GC) and/or immunosuppressive agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has been reported as a safe and effective option but only few data on renal outcome are available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy (cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional immunosuppressive regimens.2 We present the results of a multicentre cohort of patients with IgAV and cIgAN treated with RTX. Method The databases of 16 consorted European centres were investigated to screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in ≥25% glomeruli and rapid eGFR worsening at presentation), who received RTX as induction therapy. We selected patients with active renal manifestations at the time of RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or Results We identified 38 patients with IgAV and 12 patients with cIgAN who received RTX and had active renal involvement at the time of treatment. The median age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of patients were male (Table 1). The median follow-up after RTX was 41 months (IQR 18-60). Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) had eGFR ≥60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%) achieved remission; after a median of 12 months (range 9-14), four experienced a minor relapse and one had a major relapse with significant renal disease progression. Renal function remained stable in all but two patients who developed end-stage renal disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last follow-up (p=0.029). Of the 26 patients with eGFR Remission rate and ESRD-free survival were respectively 86% and 92% in patients with IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/24 (87%) patients who received RTX alone or combined to glucocorticoids but not to immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, only one patient reported a severe adverse effect related to RTX (pneumonia). Conclusion Renal involvement in adult-onset IgAV and cIgAN is frequently severe. RTX, combined or not with other immunosuppressive agents, may improve renal manifestations and is well tolerated. IgAV patients show higher remission rates and a longer ESRD-free survival as compared to cIgAN patients.

Background and Aims Proteinuria selectivity index (PSI) predicts steroid responsiveness in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Rituximab, a monoclonal antibody targeting CD20, has increasingly recognized as a potential therapy of idiopathic podocytopathies, such as MCD and FSGS, although the mechanism of action is still unrecognized and randomized controlled studies are still lacking. Currently, no tools are available to predict responsiveness to RTX. We explored the role of PSI as a potential predictor of RTX responsiveness in MCD and FSGS. Method We analysed cases of biopsy-proven MCD and FSGS followed at one single centre, who received RTX therapy. Baseline data, including proteinuria and PSI, were collected. Proteinuria was considered selective with PSI (clearance of urinary IgG/transferrin ratio) 50%) and substantial improvement of clinical symptoms. Results RTX was administered to 14 patients with MCD and 16 patients with FSGS and, of them, PSI was available before treatment for 10 and 14 patients, respectively. Baseline characteristics of the patients are shown in Table 1. Among the 24 cases with available PSI, CR was reported in 12 and PR in 5, while 9 did not respond to RTX. All patients who achieved CR and PR had selective proteinuria at baseline, while all patients with PSI >0.20 did not respond to RTX (Figure 2). Median relapse-free survival was 25.4 months. Among responders, in 10 out of 19 patients (53%) the relapse occurred between 4 and 60 months from initial treatment. No potentially life-threatening adverse events have been observed. Conclusion Selective proteinuria before treatment can predict the response to RTX in adult patients with steroid-dependent and refractory forms of MCD and FSGS.