Evolution of therapeutic management of patients with ANCA associated vasculitis in France after licensing Rituximab use.

INTRODUCTION: In 2013, rituximab was approved in France for the treatment of ANCA-associated vasculitis (AAV). The aim of the study was to compare the treatment and health events of adult incident patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), included before rituximab approval (over 2010-2012, Group 1) and those included after rituximab approval (over 2014-2017, Group 2). METHOD: Data were extracted from the French National Health Insurance database (SNDS) including outpatient health care consumption and hospital discharge forms. Comparisons between inclusion periods were performed using Wilcoxon and χ² tests. Kaplan-Meier method was used to model the duration of treatment induction, maintenance, and off-drug periods. Fine and Gray tests were used to compare treatment phase durations. RESULTS: A total of 694 GPA and 283 MPA patients were included in Group 1, while 668 GPA and 463 MPA patients were included in Group 2. Between the two inclusion periods, the proportions of patients treated with rituximab increased in the induction and maintenance phases whereas treatment with azathioprine declined. These proportions remained stable in the case of methotrexate, cyclophosphamide, and glucocorticoid-treated patients. Frequency of first-time hospitalized infections, diabetes and renal failure during the first year after inclusion increased for both groups. LIMITATIONS OF THE STUDY: This is a retrospective study based on claims data including only 76% of people covered by health insurance in France. The period studied includes the learning phase of using rituximab. This study lacks biological data and precise quantitative analysis for the use of steroids, therefore the criteria for establishing diagnosis and therapeutic choice were unknown. CONCLUSIONS: Introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids or cyclophosphamide.

Diagnosis and management of pruritus associated with chronic kidney disease in hemodialyzed patients / Diagnostic et prise en charge du prurit associé à la maladie rénale chronique chez les patients hémodialysés

Chronic kidney disease-associated pruritus (CKD-aP) is a disabling symptom which is frequent and often underestimated. Pa-MRC has a negative impact on quality of life, and is frequently accompanied by sleep disorders and depression. The approval of difelikefalin ­ a kappa opioid receptor agonist ­ in this indication requires updated recommendations. As a first step, secondary causes of pruritus without skin lesions must be ruled out, and general measures taken (emollients, psychological support, optimization of dialysis, normalization of serum calcium, phosphate and PTH in the range proposed by the KGIDO guidelines, treatment of iron deficiency). A therapeutic test with a non-sedating oral antihistamine may be proposed. If this test is negative, Pa-MRC must be strongly suspected, and its intensity (WI-NRS scale) and impact on quality of life assessed. In the case of mild Pa-MRC (WI-NRS ≤ 3), only general measures are implemented. If Pa-MRC is moderate to severe (WI-NRS ≥ 4), specific treatment with difelikefaline can be initiated for 6 months in addition to general measures. At 3 months, if the response is complete (WI-NRS score ≤ 1) or partial (decline ≥ 3 points), treatment is continued. At 6 months, if the response is complete, treatment may be discontinued with the patient's agreement; treatment is maintained if the response is partial. At 3 or 6 months, if response is insufficient (decline < 3 points) and/or in the event of intolerance, treatment is discontinued and an alternative treatment (e.g., gabapentinoids, UVB) may be considered after dermatological consultation.

Le prurit associé à la maladie rénale chronique (Pa-MRC) est un symptôme invalidant qui est fréquent et souvent sous-estimé. Le Pa-MRC a des conséquences négatives sur la qualité de vie et s'accompagne fréquemment de troubles du sommeil et de dépression. L'approbation de la difélikéfaline ­ agoniste des récepteurs opioïdes kappa ­ dans cette indication nécessite l'actualisation des recommandations. Les causes secondaires de prurit sans lésions cutanées doivent être exclues et des mesures générales doivent être prises (émollients, aide psychologique, optimisation de la dialyse, équilibre phosphocalcique avec parathormone [PTH] dans la cible KDIGO [Kidney Disease: Improving Global Outcomes], traitement de la carence martiale). Une épreuve thérapeutique avec un antihistaminique oral non sédatif peut être proposée. En cas de test négatif, il faut fortement suspecter un Pa-MRC et évaluer son intensité (échelle WI-NRS [Worst Itch Numeric Rating Scale]) et son impact sur la qualité de vie. En cas de Pa-MRC léger (WI-NRS ≤ 3), seules les mesures générales sont mises en œuvre. Si le Pa-MRC est modéré à sévère (WI-NRS ≥ 4), un traitement spécifique par difélikéfaline peut être instauré pour 6 mois en plus des mesures générales. À 3 mois, si la réponse est complète (score WI-NRS ≤ 1) ou partielle (baisse ≥ 3 points), le traitement est poursuivi. À 6 mois, si la réponse est complète, l'arrêt du traitement peut être envisagé avec l'accord du patient ; il est maintenu en cas de réponse partielle. À 3 ou 6 mois, en cas de réponse insuffisante (baisse < 3 points) et/ou d'intolérance, le traitement est interrompu et un autre traitement (par exemple, gabapentinoïdes, ultraviolet de type B [UVB]) peut être envisagé après avis dermatologique.

Pruritus associated with chronic kidney disease in hemodialysis patients: a survey in French nephrologists / Prurit associé à la maladie rénale chronique chez les patients hémodialysés : une enquête auprès des néphrologues français

Background: Chronic kidney disease-associated pruritus (CKD-aP) is common in hemodialysis patients and severely impairs their quality of life, but the practices of nephrologists remain poorly known. Methods: The objective of this on-line survey was to describe the management of CKD-aP in French nephrologists affiliated with the French-speaking Society of Nephrology, Dialysis and Transplantation (SFNDT) and involved in hemodialysis. Results: In total, 122 questionnaires were completed and 100 were usable. Nephrologists reported they personally managed a median of 52 patients; they estimated that the CKD-aP prevalence in their hemodialysis patients was a median of 10% (IQR, 6.3-17.2); 6% of nephrologists reported not following any patient with CKD-aP. In case of CKD-aP, the first-intention intervention was the evaluation of phosphocalcic metabolism (53.5%) and verification of dialysis adequacy (52%). For moderate-to-severe CKD-aP, the first-line prescription was topical therapy (71.3%), antihistamine (23.2%) and membrane change (15.9%). Patients were referred to a dermatologist mainly in case of treatment failure (86.9%) or scratching lesions (40.4%). Available treatments were considered ineffective for 50.5% of nephrologists, partially effective for 45.5% and effective for only 4%. Conclusion: These results show that according to the opinion of nephrologists, the pruritus prevalence is low in dialysis patients. This is inconsistent with studies based on systematic patient interviews, thus suggesting that pruritus is a symptom overlooked by nephrologists. In the context of the arrival of a new drug for pruritus, patients should be more questioned about this symptom in order to propose this treatment.

Introduction: Le prurit associé à l'insuffisance rénale chronique (Pa-IRC) est fréquent chez les patients hémodialysés et altère gravement leur qualité de vie, mais les pratiques des néphrologues restent mal connues. Méthodes: L'objectif de cette enquête en ligne était de décrire la prise en charge du Pa-IRC par les néphrologues français hémodialyseurs affiliés à la Société francophone de néphrologie, dialyse et transplantation (SFNDT). Résultats: Au total, 122 questionnaires ont été remplis et 100 étaient utilisables. Les néphrologues suivaient personnellement 52 patients (médiane). Ils estimaient que la prévalence du Pa-IRC chez ces patients était de 10 % (médiane ; écart interquartile : 6,3-17,2) ; 6 % des néphrologues ont déclaré ne suivre aucun patient atteint de Pa-IRC. En cas de Pa-IRC, l'intervention de première intention était l'évaluation du métabolisme phosphocalcique (53,5 %) et la vérification de la qualité de dialyse (52 %). Pour le Pa-IRC modéré à sévère, la prescription de première intention était un traitement topique (71,3 %), un antihistaminique (23,2 %) et un changement de membrane (15,9 %). Les traitements disponibles étaient considérés comme inefficaces pour 50,5 % des néphrologues, partiellement efficaces pour 45,5 % et efficaces pour seulement 4 %. Conclusion: Ces résultats montrent que selon l'opinion des néphrologues, la prévalence du prurit est faible chez les patients dialysés. Ceci est en contradiction avec les études basées sur des entretiens systématiques avec les patients, suggérant ainsi que le prurit est un symptôme sous-estimé par les néphrologues. Dans le contexte de l'arrivée d'un nouveau médicament pour le prurit, les patients devraient être davantage interrogés sur ce symptôme afin de proposer ce traitement.

Moderate-to-severe pruritus in untreated or non-responsive hemodialysis patients: results of the French prospective multicenter observational study Pruripreva.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients treated with hemodialysis, and has a negative impact on quality of life (QoL). Due to the lack of standardized diagnostic tools and frequent underreporting, pruritus prevalence remains poorly documented. Methods: Pruripreva was a prospective multicenter observational study that aimed to evaluate the prevalence of moderate to severe pruritus in a cohort of French hemodialysis patients. The primary endpoint was the rate of patients with mean Worst Itch Numerical Rating Scale (WI-NRS) score ≥4 calculated over 7 days (moderate pruritus, 4-6; severe, 7-8; very severe, 9-10). Impact of CKD-aP on QoL was analyzed according to its severity (WI-NRS), using 5-D Itch scale, EQ-5D and Short Form (SF)-12. Results: Mean WI-NRS was ≥4 in 306 patients (mean age, 66.6 years; male, 57.6%) out of 1304 and prevalence of moderate to very severe pruritus was 23.5% (95% confidence interval 21.2-25.9). Pruritus was unknown prior to the systematic screening in 37.6% of patients, and 56.4% of those affected were treated for this condition. The more severe the pruritus, the poorer the QoL according to the 5-D Itch scale, EQ-5D and SF-12. Conclusion: Moderate to very severe pruritus was reported in 23.5% of hemodialysis patients. CKD-aP was underrated although it is associated with a negative impact on QoL. These data confirm that pruritus in this setting is an underdiagnosed and underreported condition. There is an urgent demand for new therapies to treat chronic pruritus associated with CKD in hemodialysis patients.

Impact and Tolerance of Immunosuppressive Treatments in Patients Living with HIV with Inflammatory or Autoimmune Diseases.

BACKGROUND: Patients living with HIV (PLWHIV) can develop autoimmune diseases (AD) needing immunosuppressive treatments (IST). This study aims to describe the impact of IST in PLWHIV. METHODS: This was a multicentric retrospective observational study in six HIV referral centers on PLWHIV under IST for AD. Demographic factors, viral co-infections, immunovirological status before and under IST, infectious events, and their descriptions were collected and described focusing on infectious events, immunovirological variations, and IST effectiveness. RESULTS: 9480 PLWHIV were screened for inclusion. Among them, 138 (1.5%) had a history of auto-immune disease, among which 32 (23%) received IST. There was mainly spondyloarthropathy (28%) and the most commonly used IST was methotrexate. The median follow-up under IST was 3.8 years (2.7; 5.9). There were 15 infectious events (0.5 events/individuals) concerning nine patients. At the last medical follow-up, 81% of these were in remission of their AD. Under IST, there was an increase in CD4 during follow-up (629 vs. 827 CD4/mm3, p = 0.04). No HIV virological failure was noted. CONCLUSIONS: This study supports a growing evidence base that IST can be used safely and effectively in PLWHIV with careful monitoring.

Epidemiology of granulomatosis with polyangiitis and microscopic polyangiitis in adults in France.

BACKGROUND: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. The national incidence and prevalence of GPA/MPA and patient mortality remain unknown in France. A real-life study using retrospective data from the French National Health Data System was set up to describe the epidemiology and demographic characteristics of hospitalized GPA and MPA patients, overall and by disease. METHODS: All adult patients (≥18 years of age) hospitalized for GPA (ICD-10 M31.3) or MPA (ICD-10 M31.7) between 01 and 01-2010 and 31-12-2017 and affiliated to the General health insurance Scheme (covering 76% of the French population) were included in this national retrospective observational study. Descriptive analyses, univariate and multivariable logistic models, Kaplan-Meier survival analysis, and Cox models were performed. RESULTS: The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Distinction between GPA and MPA diagnosis could not be made for 303 patients (149 incident patients). In people aged over 20 years, the age-standardized incidence rates of GPA and MPA were 0.5 and 0.3/100,000 person-years, respectively and the age-standardized prevalence rates were 10 and 4/100,000 person-years, respectively. The standardized mortality ratios in GPA and MPA patients aged over 20 years were 2.0 and 2.7, respectively, and remained constant. Renal failure, pulmonary and urinary tract infections, as well as coronary disease were more frequent among MPA than GPA patients. One-year survival rates among GPA and MPA patients were 96% (95%CI 94%-97%) and 94% (92%-95%), respectively. Five-year survival rates among GPA and MPA patients were 81% (95% CI 79%-83%) and 72% (68%-75%), respectively. After adjusting for comorbidities, the risk of death was still higher in MPA (hazard ratio 1.26 [95%CI 1.06-1.50]) than in GPA patients. CONCLUSIONS: Despite advances in the therapeutic management of patients, mortality rates are still high and stable over time, highlighting the need for improved management.

Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy.

BACKGROUND: Antiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN. METHODS: Retrospective multicenter study of patients with antiphospholipid antibodies (aPL) associated with histological APSN lesions and no other nephropathy, identified through a national call for medical records. End-stage renal disease (ESRD)-free survival, thrombosis recurrence-free survival and overall survival were assessed. RESULTS: Thirty patients were included (19 women) with a median age of 40 years (34-52 years). Fifteen patients had APS, 26/28 had lupus anticoagulant, and 15/26 had triple positivity for aPL. Median eGFR was 50 (31-60) mL/min/1.73 m2. Glomerular thrombotic microangiopathy was found in 12/24 cases, fibrous intimal hyperplasia in 12/22 cases and focal cortical atrophy in 17/29 cases. Nineteen patients had moderate to severe interstitial fibrosis (>25%). Six patients developed ESRD at a median follow-up of 6.2 (1.8-9.1) years. The ESRD-free survival rates at 5 and 10 years were 80.0% (95% CI 57.6%-91.4%) and 72.7% (95% CI, 46.9%-87.4%) respectively. None of the histological factors considered was significantly associated with a decrease in eGFR at 12 months. Thrombosis recurrence-free survival was 77.8% (95% CI 48.2%-91.6%) at 10 years. Overall survival was 94% at 10 years (95% CI 65.0%-99.2%). CONCLUSIONS: The renal prognosis of isolated APSN is poor. The severe fibrotic lesions observed are suggestive of late diagnosis.

[Current status of persistent chronic hyperkalaemia in France: An expert consensus based on a Delphi approach]. / État des lieux sur l'hyperkaliémie chronique persistante en France : consensus d'experts par une approche Delphi.

INTRODUCTION: In France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed. METHODS: A consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26 voting participants among 40 invited panellists in first round) and June 2020 (20 voting participants among 26 panellists in second round). RESULTS: Persisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage 3B to stage 5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins). CONCLUSIONS: The panel expressed a need for new treatment strategies validated by clinical trials.

Antineutrophil Cytoplasm Antibody-Associated Vasculitides Valvular Impairment: Multicenter Retrospective Study and Systematic Review of the Literature.

OBJECTIVE: While myocardial impairment is a predictor of poor prognosis in antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), little is known about valvular involvement. This study aims at describing the clinical presentation, management, and outcome of endocarditis associated with AAV. METHODS: We conducted a multicenter retrospective study in centers affiliated with the French Vasculitis Study Group. We included patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic GPA with endocardial impairment. A systematic review was then performed through PubMed, Embase, and Cochrane Library from inception up to September 2020. RESULTS: The retrospective cohort included 9 patients (82%) with GPA, 1 (9%) with MPA, and 1 (9%) with unclassified AAV. Clinical presentation included acute valvular insufficiency (n = 7, 64%), cardiac failure (n = 3, 27%), dyspnea (n = 3, 27%), and no symptoms (n = 2, 18%). The aortic valve was the most frequently affected (n = 8/10, 80%), and vegetations were noted in 4 of 10 patients (40%). Six patients (55%) underwent surgical valvular replacement. No death from endocarditis was reported. The systematic review retrieved 42 patients from 40 references: 30 (71%) had GPA, 21 (50%) presented with vegetations, the aortic valve (n = 26, 62%) was the most frequently involved. Valvular replacement was required in 20 cases (48%) and 5 patients (13%) died from the endocarditic impairment. CONCLUSION: Endocarditis is a rare and potentially life-threatening manifestation of AAV. Acute valvular insufficiency may lead to urgent surgery. Implementing transthoracic echocardiography in standard assessment at baseline and follow-up of AAV might reduce the delay to diagnosis and allow earlier immunosuppressive treatment before surgery is needed.

Early Renal Recovery after the First Flare of Pauci-Immune Glomerulonephritis.

INTRODUCTION: Renal involvement is a severe manifestation of antineutrophil cytoplasmic antibody-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after the first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in the eGFR between diagnosis and the follow-up at 3 months (ΔeGFRM0-M3). METHODS: This was a retrospective study over the period 2003-2018 of incident patients in the Nord-Pas-de-Calais (France). The primary outcome was the ΔeGFRM0-M3. RESULTS: One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs. 28 ± 26 mL/min/1.73 m2, p < 0.001), with a ΔeGFRM0-M3 of 12 ± 19 mL/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs. 40 ± 24 mL/min/1.73 m2, p = 0.003). The factors significantly associated with the ΔeGFRM0-M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in the eGFR was 2.90 ± 0.06 mL/min/1.73 m2 for every 10-point gain in the percentage of cellular crescents. CONCLUSIONS: Early renal recovery after the first flare of pauci-immune glomerulonephritis occurred mainly in the first 3 months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.

ANCA-Negative Pauci-immune Necrotizing Glomerulonephritis: A Case Series and a New Clinical Classification.

RATIONALE & OBJECTIVE: Pauci-immune necrotizing glomerulonephritis (PING) is usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a minority (2%-3%) of patients with PING do not have detectable ANCA. We assessed the clinical spectrum and outcome of patients with ANCA-negative PING. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 74 patients with ANCA-negative PING diagnosed in 19 French nephrology centers between August 2006 and December 2018 were included in the series. Patients' medical files were reviewed, and kidney biopsies were centrally reexamined by pathologists who were masked to the diagnosis. FINDINGS: Median age at diagnosis was 69 (IQR, 61-76) years. The clinical and pathological features were remarkable for a high frequency of extrarenal manifestations (54%), nephrotic syndrome (32%), and endocapillary hypercellularity (31%). Three main subtypes of ANCA-negative PING were observed: infection-associated (n=9[12%]), malignancy-associated (n=6[8%]), and primary (n=57[77%]). For patients with primary PING, induction treatment included mainly corticosteroids (n=56[98%]), cyclophosphamide (n=37[65%]), and rituximab (n=5[9%]). Maintenance treatment consisted mainly of corticosteroids (n=42[74%]), azathioprine (n=18[32%]), and mycophenolate mofetil (n=11[19%]). After a median follow-up period of 28 months, 28 (38%) patients had died and 20 (27%) developed kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2). Eleven (21%) patients (9 with primary and 2 with malignancy-associated PING) relapsed. LIMITATIONS: Retrospective study and limited number of patients; electron microscopy was not performed to confirm the absence of glomerular immune deposits. CONCLUSIONS: Within the spectrum of ANCA-negative PING, infection and malignancy-associated forms represent a distinct clinical subset. This new clinical classification may inform the management of ANCA-negative PING, which remains a severe form of vasculitis with high morbidity and mortality rates despite immunosuppressive treatments.

Results of a nation-wide cohort study suggest favorable long-term outcomes of clone-targeted chemotherapy in immunotactoid glomerulopathy.

Immunotactoid glomerulopathy is a rare disease defined by glomerular microtubular immunoglobulin deposits. Since management and long-term outcomes remain poorly described, we retrospectively analyzed results of 27 adults from 21 departments of nephrology in France accrued over 19 years. Inclusion criteria were presence of glomerular Congo red-negative monotypic immunoglobulin deposits with ultrastructural microtubular organization, without evidence for cryoglobulinemic glomerulonephritis. Baseline manifestations of this cohort included: proteinuria (median 6.0 g/day), nephrotic syndrome (70%), microscopic hematuria (74%) and hypertension (56%) with a median serum creatinine of 1.5 mg/dL. Nineteen patients had detectable serum and/or urine monoclonal gammopathy. A bone marrow and/or peripheral blood clonal disorder was identified in 18 cases (16 lymphocytic and 2 plasmacytic disorders). Hematologic diagnosis was chronic/small lymphocytic lymphoma in 13, and monoclonal gammopathy of renal significance in 14 cases. Kidney biopsy showed atypical membranous in 16 or membranoproliferative glomerulonephritis in 11 cases, with microtubular monotypic IgG deposits (kappa in 17 of 27 cases), most commonly IgG1. Identical intracytoplasmic microtubules were observed in clonal lymphocytes from 5 of 10 tested patients. Among 21 patients who received alkylating agents, rituximab-based or bortezomib-based chemotherapy, 18 achieved a kidney response. After a median follow-up of 40 months, 16 patients had sustained kidney response, 7 had reached end-stage kidney disease, and 6 died. Chronic/small lymphocytic lymphoma appears as a common underlying condition in immunotactoid glomerulopathy, but clonal detection remains inconstant with routine techniques in patients with monoclonal gammopathy of renal significance. Thus, early diagnosis and hematological response after clone-targeted chemotherapy was associated with favorable outcomes. Hence, thorough pathologic and hematologic workup is key to the management of immunotactoid glomerulopathy.

Adherence to hydroxychloroquine in patients with systemic lupus: Contrasting results and weak correlation between assessment tools.

OBJECTIVES: Hydroxychloroquine (HCQ) is an anchor drug in the treatment of systemic lupus erythematosus (SLE). Adherence to HCQ is key for efficacy. Inaccurate evaluation of adherence could lead to non-justified switch to more expensive or less tolerated drugs. METHODS: Severe non-adherence rate to HCQ was estimated in a sample of SLE patients during a routine visit using blood HCQ concentration<200µg/L. Adherence was assessesd by the Medication Adherence Self-Report Inventory (MASRI)<80/100, 8-item Morisky Medication Adherence Scale (MMAS-8) ≤6/8, Health Care Provider (HCP) visual analog scale (VAS)<80/100. Same procedures were to be repeated during a further routine visit 6 to 12 months later. We described agreement and correlations between tools and compared severely non-adherent patients and others on their characteristics. RESULTS: The study involved 158 patients (86.1% females) aged 42.2±12.6 years treated with HCQ for 9.6±6.9 years. Blood HCQ concentration (mean±standard deviation) was 1046±662µg/L at visit 1 and 855±577µg/L at visit 2. At visit 1, the non-adherence rate varied from 3.2% (blood HCQ level<200µg/L) to 7.7% (MASRI), 12.4% (HCP-VAS) or 32.5% (MMAS-8). 37.8% of patients met at least one of the definitions of non-adherence. Patients' characteristics including SLE activity, damage and quality of life were similar between severely non-adherent patients and others. Correlations between blood HCQ-concentration and self-questionnaires were weak (r<0.25) and agreement between methods was poor. CONCLUSION: Blood HCQ concentration<200µg/L reveals severe non-adherence. Combining blood HCQ concentration with MASRI and MMAS-8 may help to better identify non-adherence in SLE. Agreement between methods was poor and correlations with HCQ level and SLE activity were weak.

Tubulointerstitial damage and interstitial immune cell phenotypes are useful predictors for renal survival and relapse in antineutrophil cytoplasmic antibody-associated vasculitis.

The aims of this study were to determine whether tubulointerstitial damage in the form of interstitial fibrosis/tubular atrophy and total interstitial inflammation predicted progression to end stage renal disease (ESRD) and/or renal relapse (RR) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). One hundred thirteen patients with AAV from six French centers with an index biopsy performed between 2003 and 2013 were included. Histological assessments using the AAV glomerular classification and the kidney allograft Banff classification were performed on pathological review. Biopsy tissues were also investigated by CD3, CD20, CD68, CD163, FOXP3 and RORγt immunohistochemical staining. Competing risks models were calculated. Of the 113 patients, 26 (23.0%) died during follow-up and 29 (25.6%) developed ESRD. Among the 94 patients who achieved remission by the end of induction therapy without developing ESRD, 26 (27.6%) experienced RR. The two independent prognostic factors for ESRD were the estimated glomerular filtration rate at presentation (HR 0.35; 95% CI 0.23-0.51; P < 0.0001) and IF/TA > 25% (HR 2.27; 95% CI 1.18-4.37; P = 0.014). When the distribution of interstitial immune cell phenotypes was included in a second multivariable model, the organization of lymphocytic infiltrates was also an independent predictor of ESRD (HR 2.86; 95% CI 1.35-6.1, P = 0.006). The independent risk factors for RR were a higher CD3/CD20 ratio (HR 1.39; 95% CI 1.05-1.85; P = 0.02) and the presence of RORγt positive cells (HR 2.70; 95% CI 1.11-6.54; P = 0.02). Our results highlight the prognostic value of initial histological evaluations in AAV. Measurements of tubulointerstitial damage and interstitial immune cell phenotype distributions should be considered to improve risk assessments for ESRD and RR.

Consideration of coping strategies for patients suffering from systemic lupus erythematosus: reflection for a personalised practice of patient education.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune multi-organ disease with an unpredictable course. SLE causes functional disability, changes in body appearance, and psychological distress. When faced with SLE, patients have to implement coping strategies. Therefore, the aim of this study was to describe patients' coping strategies, consider the implications for a personalised practice of patient education and evaluate patients' adherence to HCQ treatment. METHODS: One hundred and fifty-eight SLE patients receiving hydroxychloroquine (HCQ) treatment entered a prospective, non-comparative, longitudinal study aimed at describing patients' coping strategies and evaluating their adherence to the HCQ regimen. Coping strategies were evaluated using an abbreviated French version of the WCC-27 exploring 3 dimensions of coping: problem-centered coping, emotion-centered coping and search for social support. Adherence was assessed by the MASRI, the MMAS-8 and also objectively assessed by the patient's serum level of HCQ. Data collected at study entry also included disease activity: SLEDAI, and disease extent: SLICC damage index. The prevalence of anxious and depressive symptoms was evaluated with the HADS. Quality of life was evaluated using the LupusQoL questionnaire. RESULTS: Patients were clustered using an unsupervised hierarchical classification based on coping strategies. Four clusters of patients were individualised. The cluster of patients with low problem-centered coping, high emotion-centered coping and the lowest search for social support had worse quality of life and more psychological distress. We did not find any inter-cluster differences in terms of compliance to HCQ. CONCLUSIONS: Patients' knowledge is not the only parameter to consider for a personalised educational therapy: psychological parameters such as coping must also be considered to ensure the best possible quality of life. For educational therapy purposes, it is important not to group patients with the same coping style; heterogenous groups will enable patients to share their experiences and learn from the coping strategies of others.

Prognostic Value of Microscopic Hematuria after Induction of Remission in Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis.

BACKGROUND: Pauci-immune glomerulonephritis (PIGN) is a major prognostic factor in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV). Renal remission is usually defined as improvement or stabilization of serum creatinine and proteinuria levels but the significance of hematuria is unclear. We evaluated the prognostic value of microscopic hematuria in patients in remission from a first flare of PIGN. METHODS: A multicenter retrospective study was conducted of all patients with histologically proven PIGN in northern France who presented a first renal flare of AAV between 2003 and 2013. All patients received conventional induction treatment and were considered in remission. Two groups were defined by the presence (H+) or absence (H-) of hematuria (dipstick 1+ and/or cytology ≥10,000 erythrocytes/mL). The primary outcome measure was the occurrence of renal relapse (RR) and/or end-stage renal disease (ESRD). RESULTS: Eighty-six patients were included: 41 (48%) had hematuria at remission. The median follow-up time was 44 ± 34 months. There was no significant difference between the groups in terms of the primary endpoint or the number of RR. However, the survival rate without RR was significantly lower in the H+ group (p = 0.002). In multivariate analysis, risk factors for RR were hematuria at remission for relapses within 44 months (hazard ratio [HR] 4.15; 95% CI 1.15-15.01; p = 0.03) and the duration of maintenance immunosuppressive therapy (HR 0.96 per additional month; 95% CI 0.94-0.99; p = 0.002). CONCLUSION: Hematuria at remission after a first PIGN flare was not associated with ESRD but with the occurrence of RR within 44 months of remission.

Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France.

OBJECTIVE: To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria. PATIENTS AND METHODS: Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed-effects logistic regression model was used to estimate how urine pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria. RESULTS: Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0 8.0, P <0.001). CONCLUSION: Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH >7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.

Differential Determinants of Tubular Phosphate Reabsorption: Insights on Renal Excretion of Phosphates in Kidney Disease.

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.

[Sucroferric oxyhydroxide, a novel iron-based phosphate binder. Which current use in dialysis patients?] / Oxyhydroxyde sucroferrique, un nouveau chélateur des phosphates à base de fer. Quelle utilisation chez le patient dialysé ?

International guidelines suggest lowering elevated phosphorus level to the normal range in patients on dialysis. Among the phosphate-lowering strategies, phosphate binder is frequently used in addition to dietary phosphate restriction and an adequate dialysis strategy. However, serum phosphate concentration higher than 1.78mmol/L is observed in more than 40% of patients justifying the quest for new drugs. Sucroferric oxyhydroxide is one of the new iron-based agents and is available in France since May 2016. A recent international multicentre study showed this new drug to be as efficacious and non-inferior to sevelamer carbonate in magnitude of serum phosphate control. The serum phosphorus-lowering effect was maintained over 1year. When compared to carbonate sevelamer, the pill-burden was half with sucroferric oxyhydroxide because of its high phosphate binding capacity. As previously shown by experimental studies, no risk of iron accumulation was observed since iron absorption is negligible. Discolored feces and diarrhea were fairly frequent side effects. When diarrhea subsides, the tolerability of this new phosphate binder is excellent on a long-term basis.