Management of severe renal disease in anti-neutrophil-cytoplasmic-antibody-associated vasculitis: the place of rituximab and plasma exchange?

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.

Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA): a multicentric retrospective study of 63 biopsy-proven cases.

OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. METHODS: We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. RESULTS: Sixty-three patients [27 women, median age 60 years (18-83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1-296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. CONCLUSION: Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.

The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury, and/or proteinuria.

We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury and/or proteinuria and underwent a kidney biopsy in the Paris and its metropolitan area. Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between March 08 and May 19, 2020 were included. Median age was 63 years IQR [52-69]. Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney (25.5%), cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%), and diarrhea (23.4%). Almost all patients developed acute kidney injury (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while eight (17%) had alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and collapsing glomerulopathy was only observed in patients harboring a combination of APOL1 risk variants. At last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 died. The present study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Severe post-renal acute kidney injury, post-obstructive diuresis and renal recovery.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The pathophysiology of post-renal acute kidney injury (PR-AKI), i.e. caused by urinary tract obstruction, has been extensively studied in animal models but clinical studies on this subject are outdated, and/or have focused on the mechanisms of 'post-obstructive diuresis' (POD), a potentially life-threatening polyuria that can develop after the release of obstruction. In severe PR-AKI, the risk of occurrence of POD is high. POD occurrence predicts renal recovery without the persistence of severe chronic kidney failure. In the present study, the occurrence of POD and the persistence of chronic renal sequelae could be predicted early from clinical variables at admission before the release of obstruction. OBJECTIVE: • To identify predictors of post-obstructive diuresis (POD) occurrence or severe chronic renal failure (CRF) persistence after the release of urinary tract obstruction in the setting of post-renal acute kidney injury (PR-AKI). PATIENTS AND METHODS: • Bi-centre retrospective observational study of all patients with PR-AKI treated in two intensive care units (ICUs) from 1998 to 2010. • Clinical, biological and imaging characteristics on admission and after the release of obstruction were analysed with univariate and, if possible, multivariate analysis to search for predictors of (i) occurrence of POD (diuresis >4 L/day) after the release of obstruction; (ii) persistence of severe CRF (estimated glomerular filtration rate <30 mL/min/1.73 m(2), including end-stage CRF) at 3 months. RESULTS: • On admission, median (range) serum creatinine was 866 (247-3119) µmol/L. • POD occurred in 34 (63%) of the 54 analysable patients. On admission, higher serum creatinine (Odds ratio [OR] 1.002 per 1 µmol/L, 95% confidence interval [CI] 1.000-1.004, P = 0.004), higher serum bicarbonate (OR 1.36 per 1 mmol/L, 95% CI 1.13-1.65, P < 0.001), and urinary retention (OR 6.96, 95% CI 1.34-36.23, P = 0.01) independently predicted POD occurrence. • Severe CRF persisted in seven (21%) of the 34 analysable patients, including two (6%) cases of end-stage CRF. Predictors of severe CRF persistence after univariate analysis were: lower blood haemoglobin (P < 0.001) and lower serum bicarbonate (P = 0.03) on admission, longer time from admission to the release of obstruction (P = 0.01) and absence of POD (P = 0.04) after the release of obstruction. CONCLUSIONS: • In severe PR-AKI treated in ICU, POD occurrence was a frequent event that predicted renal recovery without severe CRF. • POD occurrence or severe CRF persistence could be predicted early from clinical and biological variables at admission before the release of obstruction.

Idiopathic nephrotic syndrome relapse following COVID-19 vaccination: a series of 25 cases.

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.

Can empathy be taught? A cross-sectional survey assessing training to deliver the diagnosis of end stage renal disease.

BACKGROUND: Receiving the diagnosis of kidney failure has a major impact on patients. Yet, the way in which this diagnosis should be delivered is not formally taught within our medical curriculum. To fill this gap we set up a training course of kidney failure diagnosis delivery for nephrology trainees since 2016. This study assessed the effectiveness of this educational intervention. METHODS: The primary outcome was change in the empathy score immediately after the training session and several months afterward, based on the Jefferson Scale of Physician Empathy (JSPE). Self-reported change in clinical practice was also evaluated. As control groups, we assessed empathy levels in untrained nephrology trainees (n = 26) and senior nephrologists (n = 71). Later on (>6 months) we evaluated participants' perception of changes in their clinical practice due to the training. RESULTS: Six training sessions permitted to train 46 trainees. Most respondents (76%) considered the training to have a durable effect on their clinical practice. Average empathy scores were not significantly different in pre-trained trainees (average JSPE: 103.7 ± 11.4), untrained trainees (102.8 ± 16.4; P = 0.81) and senior nephrologists (107.2 ± 13.6; P = 0.15). Participants' empathy score significantly improved after the training session (112.8 ± 13.9; P = 0.003). This improvement was sustained several months afterwards (average JSPE 110.5 ± 10.8; P = 0.04). CONCLUSION: A single 4-hour training session can have long lasting impact on empathy and clinical practice of participants. Willingness to listen, empathy and kindness are thought to be innate and instinctive skills, but they can be acquired and should be taught.

Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis.

BACKGROUND AND OBJECTIVES: Malaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide. In the modern era, the spectrum of glomerular involvement observed in patients after malarial infections remains poorly described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We therefore performed a retrospective multicenter study to assess the clinical, biologic, pathologic, and therapeutic characteristics of patients with glomerular disease demonstrated by kidney biopsy in France within 3 months of an acute malaria episode. RESULTS: We identified 23 patients (12 men), all but 1 of African ancestry and including 10 patients with concomitant HIV infection. All of the imported cases were in French citizens living in France who had recently traveled back to France from an endemic area and developed malaria after their return to France. Eleven patients had to be admitted to an intensive care unit at presentation. Plasmodium falciparum was detected in 22 patients, and Plasmodium malariae was detected in 1 patient. Kidney biopsy was performed after the successful treatment of malaria, a mean of 24 days after initial presentation. At this time, all patients displayed AKI, requiring KRT in 12 patients. Nephrotic syndrome was diagnosed in 17 patients. Pathologic findings included FSGS in 21 patients and minimal change nephrotic syndrome in 2 patients. Among patients with FSGS, 18 had collapsing glomerulopathy (including 9 patients with HIV-associated nephropathy). In four patients, immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 demonstrated the presence of the malaria antigen in tubular cells but not in podocytes or parietal epithelial cells. An analysis of the apoL1 risk genotype showed that high-risk variants were present in all seven patients tested. After a mean follow-up of 23 months, eight patients required KRT (kidney transplantation in two patients), and mean eGFR for the other patients was 51 ml/min per 1.73 m2. CONCLUSIONS: In patients of African ancestry, imported Plasmodium infection may be a new causal factor for secondary FSGS, particularly for collapsing glomerulopathy variants in an APOL1 high-risk variant background.

Regional Professionals Network to Support the Renal Epidemiology and Information Registry in Ile-de-France.

We present the regional professional network to support the Renal Epidemiology Information Network (REIN) registry in maintaining high quality data production and information analyses in Ile-De-France region. The network is based on a long term partnership between the nephrologists and a regional methodology support unit. It integrates clinical research assistants for data quality control. We also present organizational methods on maintaining the registry and enhancing information analyses and automating analyses reports.

Prognostic Factors in Anti-glomerular Basement Membrane Disease: A Multicenter Study of 119 Patients.

We report the overall and renal outcome in a French nationwide multicenter cohort of 119 patients with anti-glomerular basement membrane (anti-GBM) disease. Sixty-four patients (54%) had an exclusive renal involvement, 7 (6%) an isolated alveolar hemorrhage and 48 (40%) a combined renal and pulmonary involvement. Initial renal replacement therapy (RRT) was required in 78% of patients; 82% received plasmapheresis, 82% cyclophosphamide, and 9% rituximab. ANCA positive (28%) patients were older (70 vs. 47 years, p < 0.0001), less frequently smokers (26 vs. 54%, p = 0.03), and had less pulmonary involvement than ANCA- patients. The 5 years overall survival was 92%. Risk factors of death (n = 11, 9.2%) were age at onset [HR 4.10 per decade (1.89-8.88) p = 0.003], hypertension [HR 19.9 (2.52-157 0.2) p = 0.005], dyslipidemia [HR 11.1 (2.72-45) p = 0.0008], and need for mechanical ventilation [HR 5.20 (1.02-26.4) p = 0.047]. The use of plasmapheresis was associated with better survival [HR 0.29 (0.08-0.98) p = 0.046]. At 3 months, 55 (46%) patients had end-stage renal disease (ESRD) vs. 37 (31%) ESRD-free and 27 (23%) unevaluable with follow-up < 3 months. ESRD patients were older, more frequently female and had a higher serum creatinine level at presentation than those without ESRD. ESRD-free survival was evaluated in patients alive without ESRD at 3 months (n = 37) using a landmark approach. In conclusion, this large French nationwide study identifies prognosis factors of renal and overall survival in anti-GBM patients.

Renal granulomatoses: a retrospective study of 40 cases and review of the literature.

Renal granulomatoses represent 0.5%-0.9% of nephropathies examined by renal biopsies. Granulomas can be isolated to the kidney or associated with other tissue involvement. We describe 40 consecutive patients with renal granulomatoses, associated with pauci-immune crescentic glomerulonephritis in 2 patients and with vasculitis in another, seen in northeastern Paris hospitals between January 1991 and February 2004. The criterion for inclusion was the presence of 1 or more epithelioid granulomas in the renal interstitium. Our population of 25 men and 15 women had a median age of 53 years. All patients suffered from renal insufficiency with median creatininemia of 236.8 micromol/L (range, 124-805 micromol/L), associated with hypertension (25%), median proteinuria of 0.6 g/24 h (range, 0.08-3.00 g/24 h), microscopic hematuria (15%) and leukocyturia (22.5%). Histologic examination of extrarenal specimens detected granulomas in 82.4% of the bronchial biopsies taken, and in 100% of the 2 skin biopsies, the 2 lymph-node biopsies, and the liver and colon biopsies. The following etiologies were retained: sarcoidosis for 20 (50%) patients, drug-induced for 7 (17.5%), tuberculosis for 3 (7.5%), Wegener granulomatosis for 2 (5%), and leprosy, Mycobacterium avium infection, and Crohn disease for 1 (2.5%) patient each. No etiology could be identified for 5 (12.5%) patients. Treatment must be adapted to the etiology of each case. The renal outcome after treatment was generally favorable, with the estimated median creatinine clearance increasing from 26 mL/min (range, 5.4-80.0 mL/min) to 46.5 mL/min (range, 0-118 mL/min) after a median follow-up of 35.5 months (range, 3-158 mo). Nonetheless, 32 patients had persistent renal insufficiency; 1 required hemodialysis and another underwent renal transplantation. Sarcoidosis and medications are the most common causes of renal granulomatosis. Idiopathic and drug-induced forms do not relapse after treatment discontinuation, and remission persists at long-term follow-up.

[Surgical learning curve for creation of vascular accesses for haemodialysis: value of medico-radio-surgical collaboration]. / Apprentissage chirurgical de la création des abords vasculaires pour hémodialyse: intérêt de la collaboration médico-radio-chirurgicale.

INTRODUCTION: Creation of a vascular access (VA) for haemodialysis is a surgical procedure which comprises a failure rate related to the quality of the vessels and the operator's experience. The authors report the first 2 years of a young urologist's experience with this procedure in a local hospital in collaboration with the nephrology team. PATIENTS AND METHODS: Patients undergoing creation of VA were divided into 2 chronological groups. The patient's age and gender, the cause of renal failure, the presence of diabetes, clinical examination of the upper limb, preoperative assessment of upper limb vessels, the type of anaesthesia, the operating time and the start of dialysis after the operation, as well as the functional results of the VA at 6 months were studied. Results concerning the patients of the first period were discussed by the operator and the nephrology team. RESULTS: During the first 9 months, 28 patients were operated, corresponding to 36 operations including 32 direct fistulas. Over the following 15 months, 61 patients were operated, with the creation of 63 VAs, including 55 direct fistulas. The failure rate (thrombosis or non-functioning VA) decreased from 32.1% to 11.1% (p=0.07), while the 2 groups were globally comparable. CONCLUSION: Evaluation of a new surgical procedure shows a number of failures, as for all learning curves. However, it helps to improve the results. Collaboration with nephrologists must comprise a discussion allowing the acceptance of certain failures, as they reflect compliance with a strategy of preservation of the vascular capital and a rational attempt to avoid a non-essential proximal access or bypass graft. The support of a motivated radiology team (preoperative assessment and management of complications) and the assistance of a more experienced operator are essential.

[Cholesterol crystal embolism disease, diagnostic criteria]. / Maladie des embolies de cristaux de cholestérol, critères diagnostiques.

FROM AN EPIDEMIOLOGICAL POINT OF VIEW: With the aging of the population and increased indications for angioplasty or anticoagulant therapy, the incidence of cholesterol crystal embolism is going to increase. FROM A CLINICAL POINT OF VIEW: A systemic disease related to multiorgan distal ischemia, cholesterol crystal embolism has multiple facets. Rapidly progressive renal failure, malignant hypertension in the elderly, mesenteric ischemia, acute pulmonary edema, cutaneous ischemia or encephalopathy symptomatology may reveal cholesterol crystal embolism. THE IMPORTANCE OF DIAGNOSIS: The occurrence of such symptoms in poly-vascular patients, notably following exposure to inductive factors such as arterial catheterism, anticoagulant therapy or cardiac or vascular surgery is highly suggestive of the diagnosis. The lack of its knowledge can lead to inappropriate anticoagulant therapy and useless arteriography, which may even prolong or worsen cholesterol crystal embolism.

[Medical management of post-obstruction diuresis syndromes]. / Prise en charge médicale des syndromes de levée d'obstacle.

The presence of urinary tract obstruction affects the proximal urinary tract by altering renal filtration and excretion functions, resulting in accumulation of electrolytes. Many pathophysiological mechanisms are also involved during obstruction and may be expressed secondarily. For example, relief of obstruction, which restores free flow of urine, is accompanied by marked diuresis and electrolyte disorders. The post-obstruction diuresis syndrome can lead to dehydration, or even shock and acute renal failure. Strict and specialized monitoring is required during the post-obstruction phase. Medical management is designed to avoid serious haemodynamic and metabolic disorders.

[Treatment of chronic kidney disease: therapeutic strategy]. / Traitement de l'insuffisance rénale chronique : stratégie thérapeutique.

The objectives are to slow the progression of chronic kidney disease (CKD), to take all the cardiovascular risk factors into account, to screen for and treat specific complications and to prepare, if necessary, for renal replacement treatment (transplantation or dialysis). The principal treatment targets are: blood pressure less than 130/80 mmHg and proteinuria less than 0.5 g/day (ratio of proteinuria/creatinuria <50mg/mmol). The first-line treatment to reach these goals is angiotensin conversion enzyme inhibitors (ACE inhibitors), combined with diet and other life style changes. The periodicity of clinical and laboratory assessments depends on the CKD stage, the speed of disease progression and the need to reassess the impact of therapeutic interventions. Comprehensive multidisciplinary management can slow or even stop the progression of CKD and reduce its cardiovascular complications, which are the leading cause of death in these patients.

Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis.

Rapidly progressive glomerulonephritis (RPGN) is a life-threatening clinical syndrome and a morphological manifestation of severe glomerular injury that is marked by a proliferative histological pattern ('crescents') with accumulation of T cells and macrophages and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the epidermal growth factor receptor (EGFR, also known as ErbB1) in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Likewise, pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 d after the induction of experimental RPGN. This suggests that targeting the HB-EGF-EGFR pathway could also be beneficial in treatment of human RPGN.

Glomerular lesions in patients with sickle cell disease.

Sickle cell disease (SCD) is an increasing cause of chronic kidney disease, but the spectrum of glomerular lesions and their underlying mechanisms remain poorly described. We reviewed 18 renal biopsies from patients with SCD and glomerular involvement and studied the expression of hypoxic markers in the biopsy specimens. Four histopathologic variants were distinguished: focal segmental glomerulosclerosis (FSGS) (39%), membranoproliferative glomerulonephritis (28%), thrombotic microangiopathy glomerulopathy (17%), and specific sickle cell disease glomerulopathy (17%). Chronic organ damage and history of acute chest syndrome were associated with the occurrence of SCD glomerulopathy. All patients exhibited macroalbuminuria but only 6 patients displayed impaired renal function. SCD was not associated with a specific FSGS histologic variant. Long-term follow-up analysis revealed that 50% of patients exhibited chronic kidney disease. Regardless of the histologic variants, immunohistochemistry did not reveal a specific induction of hypoxic markers (inducible nitric oxide synthase [iNOS], nitrotyrosine, hypoxia-inducible factor [HIF]-1 alpha) at the time of renal biopsy. This large study shows that a wide spectrum of glomerular lesions is associated with SCD. Whatever lesions are observed, the renal prognosis is poor, and early renoprotective treatment is necessary. Hypoxic state does not seem to play a key role in the progression of glomerular lesions, but its potential role at an early stage of glomerular injury requires further investigation.

Rituximab in severe lupus nephritis: early B-cell depletion affects long-term renal outcome.

BACKGROUND AND OBJECTIVES: Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors analyzed clinical and histologic data of 20 patients who were treated with rituximab for lupus nephritis and followed up for at least 12 mo. RESULTS: Nineteen women and one man received rituximab as induction treatment for an active class IV (15 cases) or class V (5 cases) lupus nephritis. Rituximab was given for lupus nephritis refractory to standard treatment (12 cases), for relapsing disease (6 cases), or as first-line treatment (2 cases). Three patients received cyclophosphamide concomitantly with rituximab. Ten received new injections of rituximab as maintenance therapy. Side effects included mainly five infections and four moderate neutropenias. After a median follow-up of 22 mo, complete or partial renal remission was obtained in 12 patients (60%). Lupus nephritis relapsed in one patient, who responded to a new course of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ethnicity and hypoalbuminemia, was strongly associated with renal response. Rapidly progressive glomerulonephritis did not respond to rituximab. CONCLUSION: Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B cell depletion is obtained.