Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group.

The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.

Using the consolidated framework for implementation research to identify challenges and opportunities for implementing a reproductive health education program into sickle cell disease care.

BACKGROUND: As survival rates for individuals with sickle cell disease (SCD) increase, calls have been made to improve their reproductive healthcare and outcomes. The research team created a web-based program entitled Fertility edUcaTion to Understand ReproductivE health in Sickle cell disease (FUTURES). The study aim was to use the Consolidated Framework for Implementation Research (CFIR) during pre-implementation to identify challenges and opportunities from the individual to systems level of implementation to ultimately optimize the integration of FUTURES into clinical practice. METHODS: Semi-structured interviews were conducted with clinicians, research team members, and adolescent and young adult (AYA) males with SCD and their caregivers who participated in pilot testing. Interviews (N = 31) were coded inductively and then mapped onto CFIR domains (i.e., outer setting, inner setting, characteristics of individuals, and intervention characteristics). RESULTS: Research team interviews indicated the lack of universal guidelines for reproductive care in this population and gaps in reproductive health knowledge as key reasons for developing FUTURES, also highlighting the importance of collaboration with community members during development. Clinicians reported intraorganizational communication as essential to implementing FUTURES and discussed challenges in addressing reproductive health due to competing priorities. Clinicians, AYAs, and caregivers reported positive views of FUTURES regarding length, engagement, accessibility, and content. Suggestions for the best setting and timing for implementation varied. CONCLUSIONS: Using CFIR during the pre-implementation phase highlighted challenges and opportunities regarding integrating this program into SCD care. These findings will inform adaptation and further testing of FUTURES to ensure effective implementation of this novel education program.

Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.

Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection.

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.

Results from the IRoc-GN international registry of patients with COVID-19 and glomerular disease suggest close monitoring.

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels.

High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening.

BACKGROUND: Strategies to minimize the risk of transmission and acquisition of COVID-19 infection in patients with ESKD receiving in-center hemodialysis have been rapidly implemented across the globe. Despite these interventions, confirmed COVID-19 infection rates have been high in the United Kingdom. Prevalence of asymptomatic disease in an adult hemodialysis population has not been reported. Also, to our knowledge, the development of humoral response to SARS-CoV-2 has not been previously reported in this population. Although serologic testing does not provide information on the infectivity of patients, seroprevalence studies may enable investigation of exposure within dialysis units and hence, assessment of current screening strategies. METHODS: To investigate the seroprevalence of SARS-CoV-2 antibodies in a hemodialysis population, we used the Abbott IgG assay with the Architect system to test serum samples from 356 patients receiving in-center hemodialysis for SARS-CoV-2 antibodies. RESULTS: Of 356 patients, 121 had been symptomatic when screened before a dialysis session and received an RT-PCR test; 79 (22.2% of the total study population) tested positive for COVID-19. Serologic testing of all 356 patients found 129 (36.2%) who tested positive for SARS-CoV-2 antibodies. Only two patients with PCR-confirmed infection did not seroconvert. Of the 129 patients with SARS-CoV-2 antibodies, 52 (40.3%) had asymptomatic disease or undetected disease by PCR testing alone. CONCLUSIONS: We found a high seroprevalence of SARS-CoV-2 antibodies in patients receiving in-center hemodialysis. Serologic evidence of previous infection in asymptomatic or PCR-negative patients suggests that current diagnostic screening strategies may be limited in their ability to detect acute infection.

A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis.

Objectives: Glucocorticoids (GCs) are a mainstay of treatment for patients with ANCA-associated vasculitis (AAV) but are associated with significant adverse effects. Effective remission induction in severe AAV using extremely limited GC exposure has not been attempted. We tested an early rapid GC withdrawal induction regimen for patients with severe AAV. Methods: Patients with active MPO- or PR3-ANCA vasculitis or ANCA-negative pauci-immune glomerulonephritis were included. Induction treatment consisted of two doses of rituximab, 3 months of low-dose CYC and a short course of oral GC (for between 1 and 2 weeks). Clinical, biochemical and immunological outcomes as well as adverse events were recorded. Results: A total of 49 patients were included, with at least 12 months of follow-up in 46. All patients achieved remission, with decreases observed in creatinine, proteinuria, CRP, ANCA level and BVAS. Three patients requiring dialysis at presentation became dialysis independent. Two patients required the introduction of maintenance GC for treatment of vasculitis. Overall outcomes were comparable to those of two matched cohorts (n = 172) from previous European Vasculitis Society (EUVAS) trials, but with lower total exposure to CYC and GCs (P < 0.001) and reduced rates of severe infections (P = 0.02) compared with the RITUXVAS (rituximab versus cyclophosphamide in AAV) trial. We found no new cases of diabetes in the first year compared with historic rates of 8.2% from the EUVAS trials (P = 0.04). Conclusion: Early GC withdrawal in severe AAV is as effective for remission induction as the standard of care and is associated with reduced GC-related adverse events.

Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis.

Background: Current guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organ-threatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), although few studies have examined the efficacy and safety of these agents in combination. Methods: We conducted a single-centre cohort study of 66 patients treated with a combination of oral corticosteroids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of azathioprine and tapered steroid for the treatment of biopsy-proven renal involvement in AAV. Patients were followed for a median of 56 months. Case-control analysis with 198 propensity-matched cases from European Vasculitis Study Group (EUVAS) trials compared long-term differences in relapse-free, renal and patient survival. Results: At entry, the median Birmingham Vasculitis Activity Score (BVAS) was 19 and estimated glomerular filtration rate was 25 mL/min. Cumulative doses of rituximab, cyclophosphamide and corticosteroids were 2, 3 and 4.2 g, respectively, at 6 months. A total of 94% of patients achieved disease remission by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%, respectively, at 5 years. A total of 84% achieved ANCA-negative status and 57% remained B cell deplete at 2 years, which was associated with low rates of major relapse (15% at 5 years). The serious infection rate during long-term follow-up was 1.24 per 10 patient-years. Treatment with this regimen was associated with a reduced risk of death {hazard ratio [HR] 0.29 [95% confidence interval (CI) 0.125-0.675], P = 0.004}, progression to end-stage renal disease (ESRD) [HR 0.20 (95% CI 0.06-0.65), P = 0.007] and relapse [HR 0.49 (95% CI 0.25-0.97), P = 0.04] compared with propensity-matched patients enrolled in EUVAS trials. Conclusions: This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.

Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial.

BACKGROUND: Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate. METHODS: Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function. RESULTS: 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment. CONCLUSIONS: Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN. TRIAL REGISTRATION: This trial is registered with EudraCTN2008-001009-41 . Trial registration date 2008-10-08.

The natural history of immunoglobulin M nephropathy in adults.

BACKGROUND: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis characterized by diffuse mesangial deposition of IgM. IgM nephropathy has been a controversial diagnosis since it was first reported, and there are few data identifying specific pathological features that predict the risk of progression of renal disease. METHODS: We identified 57 cases of IgM nephropathy among 3220 adults undergoing renal biopsy at our institution. Biopsies had to satisfy the following three criteria to meet the definition of IgM nephropathy in this study: (i) dominant mesangial staining for IgM, (ii) mesangial deposits on electron microscopy (EM) and (iii) exclusion of systemic disease. RESULTS: The median age was 42 years and 24 patients were male. Thirty-nine per cent of patients presented with the nephrotic syndrome, 49% presented with non-nephrotic proteinuria and 39% had eGFR <60 mL/min. The median post-biopsy follow-up was 40 months and serum creatinine had doubled in 31% by 5 years. Of histological parameters, glomerular sclerosis and tubular atrophy, but not mesangial proliferation, were risk factors for renal insufficiency. Thirty-nine per cent of nephrotic patients achieved complete remission, and outcome was significantly worse in those who did not respond to treatment. Focal segmental glomerulosclerosis was diagnosed in 80% of those undergoing repeat renal biopsy, despite ongoing mesangial IgM deposition. CONCLUSIONS: We propose criteria for a consensus definition of IgM nephropathy.

Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment.

Background: Endocapillary hypercellularity independently predicts renal outcome in immunoglobulin A nephropathy (IgAN). Mycophenolate mofetil (MMF) treatment is offered to patients presenting to the Imperial College Renal and Transplant Centre with IgAN and histological evidence of endocapillary hypercellularity. Clinical trials of MMF in IgAN have been inconclusive and have been limited by a lack of specific histological inclusion and exclusion criteria when recruiting patients. Evidence of histological improvement following MMF treatment would support its therapeutic use. We therefore reviewed histological changes after MMF therapy in a cohort of IgAN patients. Method: Eighteen IgAN patients with native renal biopsies before and after repeated MMF treatment were identified. Patients were excluded if they had received any other immunosuppressive therapy, including corticosteroids. On the basis of the Oxford Classification of IgAN, we reviewed histological changes after MMF treatment. Results: Nine patients (50%) were male. At diagnostic renal biopsy, the median age was 35 years [interquartile range (IQR) 30-41], serum creatinine was 97 µmol/L (IQR 79-153) and urine protein creatinine ratio (UPCR) was 146 mg/mmol (IQR 98-212). The median time between biopsies was 24 months (range 9-41). Following MMF treatment, repeat biopsy demonstrated statistically significant improvement in the mean percentage of glomeruli showing endocapillary hypercellularity and cellular/fibrocellular crescents. There was no change in mesangial hypercellularity, segmental sclerosis or tubular atrophy scores. Mesangial IgA deposition was also significantly reduced. Histopathological improvement persisted after the cessation of MMF therapy, suggesting that 2 years of treatment is adequate for benefit. The median serum creatinine remained stable at 3 years follow-up at 104 µmol/L (IQR 79-147). Conclusion: MMF treatment is associated with histopathological improvement in IgAN.

Impending relapse of myelodysplastic syndrome after allogeneic transplant is difficult to diagnose and requires a multi-modal approach.

BACKGROUND: The only potentially curative therapy for myelodysplastic syndrome is allogeneic hematopoietic cell transplant; unfortunately, there is a high relapse rate. The objective of this study was to perform a detailed clinicopathologic study of patients with relapsed myeloid neoplasm following allogeneic hematopoietic cell transplant for myelodysplastic syndrome. METHODS: Pre-transplant, post-transplant, and relapse bone marrow and peripheral blood morphologic features (including dysplasia) were retrospectively evaluated by study authors. Clinical features and results of cytogenetic analysis and engraftment/chimerism studies were obtained from the medical record. RESULTS: Our study describes 21 patients with a median time to relapse of 6 months (range 2-82). Ten of the patients relapsed with higher grade disease, including six with overt acute myeloid leukemia. Pre-transplant megakaryocyte dysplasia was associated with dysplastic megakaryocytes in the relapse specimen; however, neither erythroid dysplasia nor granulocytic dysplasia were associated with their counterpart in the relapse specimen. Relapse specimens had a lower marrow cellularity and higher blast percentage than pre-transplant disease. Cytogenetic comparisons before and after transplant showed variety, including clonal evolution (22%), the same abnormal clone (33%), or a different abnormal clone (22%). CONCLUSIONS: Our detailed review of post-transplant marrow biopsies prior to relapse highlights the difficulty in diagnosing relapse and particularly impending relapse.

Nodular Lymphocyte Predominant Hodgkin Lymphoma Presenting With Unilateral Orbital Involvement.

A 40-year-old white woman presented to her general ophthalmologist for swelling of the left upper eyelid that began approximately 6 months before. CT scan of the orbits with and without contrast demonstrated homogenous enhancement of the left lacrimal gland. Examination was notable for left hypoglobus and proptosis. The patient underwent left lateral orbitotomy with biopsy of the mass and frozen section analysis showed lymphoid infiltrates. Subsequent histopathologic diagnosis was consistent with nodular lymphocyte predominant Hodgkin lymphoma, a rare subtype of Hodgkin lymphoma that has only once been previously reported in the orbit. The authors review the case and the relevant literature.

Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series.

OBJECTIVES: B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanized anti-CD20 mAb that has shown efficacy in the treatment of haematological malignancy and RA. The use of ofatumumab in the treatment of AAV has not previously been reported. METHODS: This study was based on a case series of eight patients who received ofatumumab, in conjunction with low-dose CYC and oral steroids, in the treatment of AAV. RESULTS: Eight patients received ofatumumab: seven for remission induction in active disease (three relapsing; four with new disease) and one for remission maintenance. B cell depletion was achieved in all patients by 1 month, and was sustained for at least 6 months. All patients with active disease achieved clinical remission (BVAS of zero, or BVAS ⩽5 if all scores due to persistent urinary abnormalities in the presence of stable or improving renal function) by 3 months. This was associated with a rapid fall in ANCA titres, reduced inflammatory responses and improvements in renal function. At 12 months, three patients had repopulated B cells associated with the recurrence of circulating ANCAs, although no patients experienced major clinical relapse in the first 24 months. No unexpected side effects were observed. CONCLUSION: Treatment with ofatumumab resulted in similar serological and clinical responses to those seen in previous cohorts treated at our centre with a comparable CS, CYC and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab.

Necrotizing and crescentic glomerulonephritis presenting with preserved renal function in patients with underlying multisystem autoimmune disease: a retrospective case series.

OBJECTIVE: Necrotizing and crescentic GN usually presents with rapidly declining renal function, often in association with multisystem autoimmune disease, with a poor outcome if left untreated. We aimed to describe the features of patients who have presented with these histopathological findings but minimal disturbance of renal function. METHODS: We conducted a retrospective review (1995-2011) of all adult patients with native renal biopsy-proven necrotizing or crescentic GN and normal serum creatinine (<120 µmol/l) at our centre. RESULTS: Thirty-eight patients were identified. The median creatinine at presentation was 84 µmol/l and the median proportion of glomeruli affected by necrosis or crescents was 32%. Clinicopathological diagnoses were ANCA-associated GN (74%), LN (18%), anti-GBM disease (5%) and HScP (3%). Only 18% of cases had pre-existing diagnoses of underlying multisystem autoimmune disease, although the majority (89%) had extra-renal manifestations accompanying the renal diagnosis. All patients received immunosuppression and most had good long-term renal outcomes (median duration of follow-up 50 months), although two progressed to end-stage renal disease within 3 years. We estimate that renal biopsy had an important influence on treatment decisions in 82% of cases. CONCLUSION: Necrotizing and crescentic GN may present in patients with no or only minor disturbance of renal function. This often occurs in patients with underlying systemic autoimmune disease; early referral for biopsy may affect management and improve long-term outcomes in these cases.

Long-term outcome of anti-neutrophil cytoplasm antibody-associated glomerulonephritis: evaluation of the international histological classification and other prognostic factors.

BACKGROUND: Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis with renal involvement requires treatment with potentially toxic drugs to reduce morbidity and mortality, and there is a major challenge to determine clinical and histological features predictive of renal prognosis. The aim of our study was to evaluate the use of the 2010 international histological classification for ANCA-associated glomerulonephritis (AAGN) as a predictor of renal outcome when used in conjunction with other prognostic factors. METHODS: One hundred and four patients with AAGN treated at our centre were included: 23 were classified as focal, 26 as crescentic, 48 as mixed and 7 as sclerotic. Renal outcomes were based on estimated glomerular filtration rate (eGFR) at 1 and 5 years, and on renal survival. RESULTS: By univariate analysis, patients in the focal class had the best renal outcome, those in the sclerotic class the worst outcome, and those in the mixed and crescentic classes had intermediate renal survival. There was no significant difference in outcome between the mixed and crescentic classes. In multivariate models, histological class did not improve model fit or associate with renal outcome after adjusting for established prognostic factors. Lower percentage of normal glomeruli, greater degree of tubular atrophy (TA), MPO-ANCA positivity, increasing age and lower starting eGFR, all correlated with poorer renal outcomes. CONCLUSIONS: We conclude that, in our cohort of patients, the international histological classification is predictive of renal outcome in AAGN, but did not appear to be additionally informative over other established prognostic factors in multivariate analysis. However, it may be of value to combine the current histological classification with other established parameters, such as TA and percentage normal glomeruli.

Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids.

OBJECTIVES: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN. METHODS: We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with life-threatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction. RESULTS: A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode. CONCLUSIONS: The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.