Intra-Alveolar Haemorrhage Complicating IgA Vasculitis: A Case Report, Literature Review and Discussion of Treatment

Introduction: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis with IgA-dominant immune deposits. IgAV frequently involves the skin, gastrointestinal tract, joints and kidneys. In contrast to other types of small-vessel vasculitis, IgAV is rarely complicated by intraalveolar haemorrhage (IAH). Methods/Results: We describe a patient with relapsing bladder cancer who presented with IAH during the course of IgAV successfully treated with corticosteroids alone. Conclusion: This case report reminds us that IgAV can manifest with IAH. There are no robust data to support the systematic use of cyclophosphamide or plasma exchange as first-line therapy for IgAV with IA

IgA Vasculitis and IgA Nephropathy: Same Disease?

Many authors suggested that IgA Vasculitis (IgAV) and IgA Nephropathy (IgAN) would be two clinical manifestations of the same disease; in particular, that IgAV would be the systemic form of the IgAN. A limited number of studies have included sufficient children or adults with IgAN or IgAV (with or without nephropathy) and followed long enough to conclude on differences or similarities in terms of clinical, biological or histological presentation, physiopathology, genetics or prognosis. All therapeutic trials available on IgAN excluded patients with vasculitis. IgAV and IgAN could represent different extremities of a continuous spectrum of the same disease. Due to skin rash, patients with IgAV are diagnosed precociously. Conversely, because of the absence of any clinical signs, a renal biopsy is practiced for patients with an IgAN to confirm nephropathy at any time of the evolution of the disease, which could explain the frequent chronic lesions at diagnosis. Nevertheless, the question that remains unsolved is why do patients with IgAN not have skin lesions and some patients with IgAV not have nephropathy? Larger clinical studies are needed, including both diseases, with a common histological classification, and stratified on age and genetic background to assess renal prognosis and therapeutic strategies

PURPURA RHUMATOIDE DE L'ADULTE AVEC ATTEINTE RENALE (ETUDE RETROSPECTIVE DE 250 CAS)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Multicentre, randomised, economic evaluation of a web-based interactive education platform, simple or enhanced, for patients with end-stage renal disease: the PIC-R trial protocol

International audienceIntroduction End-stage renal disease (ESRD) affects 84 000 persons in France and costs an estimated €4.2 billion. Education about their disease empowers patients and allows improved management of their disease and better health outcomes. This study aims to explore whether the addition of an interactive web-based platform to patient education is effective and cost-effective and additionally whether complementing the platform with social functions and features improves its performance.Methods and analysis Patients with severe, ESRD or post-transplant will be randomised 1:1:1 to either standard therapeutic education; or education using a specific application; or the enhanced interactive app with social features. The total follow-up duration is 18 months. Primary endpoint is the cost utility of using app-based therapeutic intervention; secondary endpoints are: compliance with treatment guidelines, app use (professionals and patients), patients’ satisfaction, budget impact analysis.Ethics and dissemination The findings will inform the deployment and reimbursement of the application. The study has ethical approval by the Ile de France ethics committee. Dissemination of the results will be presented at conferences and in peer-reviewed publications

Multicentre, randomised, economic evaluation of a web-based interactive education platform, simple or enhanced, for patients with end-stage renal disease: the PIC-R trial protocol

International audienceIntroduction End-stage renal disease (ESRD) affects 84 000 persons in France and costs an estimated €4.2 billion. Education about their disease empowers patients and allows improved management of their disease and better health outcomes. This study aims to explore whether the addition of an interactive web-based platform to patient education is effective and cost-effective and additionally whether complementing the platform with social functions and features improves its performance.Methods and analysis Patients with severe, ESRD or post-transplant will be randomised 1:1:1 to either standard therapeutic education; or education using a specific application; or the enhanced interactive app with social features. The total follow-up duration is 18 months. Primary endpoint is the cost utility of using app-based therapeutic intervention; secondary endpoints are: compliance with treatment guidelines, app use (professionals and patients), patients’ satisfaction, budget impact analysis.Ethics and dissemination The findings will inform the deployment and reimbursement of the application. The study has ethical approval by the Ile de France ethics committee. Dissemination of the results will be presented at conferences and in peer-reviewed publications

TGF-α Mediates Genetic Susceptibility to Chronic Kidney Disease

The mechanisms of progression of chronic kidney disease (CKD) are poorly understood. Epidemiologic studies suggest a strong genetic component, but the genes that contribute to the onset and progression of CKD are largely unknown. Here, we applied an experimental model of CKD (75% excision of total renal mass) to six different strains of mice and found that only the FVB/N strain developed renal lesions. We performed a genome-scan analysis in mice generated by back-crossing resistant and sensitive strains; we identified a major susceptibility locus (Ckdp1) on chromosome 6, which corresponds to regions on human chromosome 2 and 3 that link with CKD progression. In silico analysis revealed that the locus includes the gene encoding the EGF receptor (EGFR) ligand TGF-α. TGF-α protein levels markedly increased after nephron reduction exclusively in FVB/N mice, and this increase preceded the development of renal lesions. Furthermore, pharmacologic inhibition of EGFR prevented the development of renal lesions in the sensitive FVB/N strain. These data suggest that variable TGF-α expression may explain, in part, the genetic susceptibility to CKD progression. EGFR inhibition may be a therapeutic strategy to counteract the genetic predisposition to CKD

Biomarkers of IgA vasculitis nephritis in children.

Henoch-Schönlein purpura is a systemic vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis

Recruitment of CXCR3+ T cells into injured tissues in adult IgA vasculitis patients correlates with disease activity

International audienceObjectives: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. Methods: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cyto-metry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by im-munohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age-and sex-matched healthy controls.Results: We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria.Conclusion: Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity

Efficacy and safety of methylprednisolone pulse followed by oral prednisone vs. oral prednisone alone in sarcoidosis tubulointerstitial nephritis: a randomized, open-label, controlled clinical trial

International audienceABSTRACT Background We determine the benefit of pulsed methylprednisolone for improving kidney function in patients with sarcoidosis tubulointerstitial nephritis. Methods We conducted a multicenter, prospective, randomized, open-label, controlled trial in patients with biopsy-proven acute tubulointerstitial nephritis caused by sarcoidosis at 21 sites in France. Patients were randomly assigned to receive a methylprednisolone pulse 15 mg/kg/day for 3 days, then oral prednisone (MP group) or oral prednisone 1 mg/kg/day alone (PRD group). The primary end point was a positive response at 3 months, defined as a doubling of estimated glomerular filtration rate (eGFR) compared with the eGFR before randomization. Results We randomized 40 participants. Baseline eGFR before PRD was 22 mL/min/1.73m2 {interquartile range [IQR], 16–44} and before MP was 25 mL/min/1.73m2 (IQR, 22–36) (P = .3). The two groups did not differ in underlying pathological lesions, including mean percentage of interstitial fibrosis and intensity of interstitial infiltrate. In the intent-to-treat population, the median eGFR at 3 months did not significantly differ between the PRD and MP groups: 45 (IQR, 34–74) and 46 (IQR, 39–65) mL/min/1.73m2. The primary end point at 3 months was achieved in 16 of 20 (80%) PRD patients and 10 of 20 (50%) MP patients (P = .0467). The eGFR was similar between the two groups after 1, 3, 6, and 12 months of treatment. For both groups, eGFR at 1 month was strongly correlated with eGFR at 12 months (P &lt; .0001). The two groups did not differ in severe adverse events. Conclusion Compared with a standard oral steroid regimen, intravenous MP may have no supplemental benefit for renal function in patients with tubulointerstitial nephritis caused by sarcoidosis. Trial Registration: ClinicalTrials.gov: NCT01652417; EudraCT: 2012–000149-1