Evangéline Pillebout

Addition of cyclophosphamide to steroids provides no benefit compared with steroids alone in treating adult patients with severe Henoch Schönlein Purpura

Henoch Schönlein Purpura (HSP) is a common disease in children, usually associated with a good prognosis. In adults there are no prospective studies concerning its prognosis or treatment, especially in cases of severe visceral involvement. Here we compared steroid therapy without or with cyclophosphamide co-treatment in adults with severe HSP in a 12-month, multi-center, prospective, open-label trial that treated 54 adults with biopsy-proven HSP including proliferative glomerulonephritis and severe visceral manifestations. All received steroids; however, 25 were randomized to also receive cyclophosphamide. The primary endpoint that occurred in three patients in each group was complete disease remission defined as zero on the Birmingham Vasculitis Activity Score with no persistent or new clinical and/or biological vasculitis at 6 months. No patient had active visceral involvement. The secondary endpoints were renal outcome, deaths, and adverse events at 12 months. Renal function, proteinuria, safety data, incidence of diabetes, and severe infections were similar between the two groups. At the last follow-up, renal function remained stable. The small population size of our study does not permit definitive conclusions; however, we suggest that treatment of adults with severe HSP by adding cyclophosphamide provides no benefit compared with steroids alone.

Transglutaminase is essential for IgA nephropathy development acting through IgA receptors

Transglutaminase 2 is required for the development of IgA nephropathy.

IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects.

Immunoglobulin A (IgA) vasculitis, formerly called Henoch-Schönlein purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. IgA vasculitis is more common among children than adults, with more severe disease in adults. Gastrointestinal and renal involvements represent the principal causes of morbidity and mortality in adults. Factors associated with long-term end-stage renal disease (ESRD) include baseline renal function impairment and baseline proteinuria >1 or 1.5 g/day, and on renal biopsy degree of interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis. Management of IgA vasculitis in adults is rendered difficult for clinicians because of the absence of correlation between initial presentation and long-term renal outcome, and the possible occurrence of spontaneous remission in patients with severe presentation or, in contrast, possible evolution to ESRD in patients with mild symptoms. Treatment is often symptomatic because disease course is usually benign. Treatment of severe involvement, including severe gastrointestinal complications or proliferative glomerulonephritis, remains controversial, with no evidence that corticosteroids or immunosuppressive agents improved long-term outcome. Prospective, randomized, controlled trials are thus needed to analyze the benefit-risk ratio of such treatments.

Autoimmune diseases in HIV-infected patients: 52 cases and literature review

OBJECTIVES 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.

Successful outcome using rituximab as the only immunomodulation in Henoch-Schonlein purpura: case report

In the current report, we describe a patient with moderate nephritis and severe skin Henoch Schönlein purpura (HSP) who has been treated with rituximab. Complete and sustained skin and renal remission resulted from the treatment. Thus, further studies are required to confirm the efficacy of rituximab as first-line treatment in HSP, and it might be an interesting new therapeutic option.

Gluten exacerbates IgA nephropathy in humanized mice through gliadin–CD89 interaction

IgA1 complexes containing deglycosylated IgA1, IgG autoantibodies, and a soluble form of the IgA receptor (sCD89), are hallmarks of IgA nephropathy (IgAN). Food antigens, notably gluten, are associated with increased mucosal response and IgAN onset, but their implication in the pathology remains unknown. Here, an IgAN mouse model expressing human IgA1 and CD89 was used to examine the role of gluten in IgAN. Mice were given a gluten-free diet for three generations to produce gluten sensitivity, and then challenged for 30 days with a gluten diet. A gluten-free diet resulted in a decrease of mesangial IgA1 deposits, transferrin 1 receptor, and transglutaminase 2 expression, as well as hematuria. Mice on a gluten-free diet lacked IgA1-sCD89 complexes in serum and kidney eluates. Disease severity depended on gluten and CD89, as shown by reappearance of IgAN features in mice on a gluten diet and by direct binding of the gluten-subcomponent gliadin to sCD89. A gluten diet exacerbated intestinal IgA1 secretion, inflammation, and villous atrophy, and increased serum IgA1 anti-gliadin antibodies, which correlated with proteinuria in mice and patients. Moreover, early treatment of humanized mice with a gluten-free diet prevented mesangial IgA1 deposits and hematuria. Thus, gliadin-CD89 interaction may aggravate IgAN development through induction of IgA1-sCD89 complex formation and a mucosal immune response. Hence, early-stage treatment with a gluten-free diet could be beneficial to prevent disease.

Pulsatile perfusion preservation for expanded-criteria donors kidneys: Impact on delayed graft function rate

Purpose Expanded criteria donors (ECD) kidneys are a potential solution to organ shortage, but exhibit more delayed graft function (DGF). We conducted a prospective controlled study aiming to evaluate the impact of Pulsatile Perfusion Preservation (PPP) on DGF rate. Methods Inclusion criteria were: 1) ECD definition (any brain-dead donor aged > 60 years or aged 50-60 years with at least 2 of the following: history of hypertension, terminal serum creatinin level ≥ 1.5 mg/dL, death resulting from a cerebrovascular accident; 2) Donor prolonged circulatory arrest (> 20 mn); 3) previsible cold ischemia time longer than 24 hours. In each pair of kidneys, one organ was preserved with PPP and the other organ was preserved in static cold storage. Results From February 2007 to September 2009, a total of 22 donors (44 recipients) were included. Recipients were comparable in the two groups with respect to demographic and immunological data. The rate of DGF was significantly lower (9% vs. 31.8%, p=0.021) in the PPP group. At 1, 3, and 12 months, renal function was comparable in the two groups. Conclusions Pulsatile Perfusion Preservation significantly reduced DGF rate in ECD kidney transplantation.

Chronic interstitial nephritis in an HIV type-1-infected patient receiving ritonavir-boosted atazanavir.

Here, we report a case of chronic granulomatous tubulo-interstitial nephritis related to atazanavir crystals in a HIV type-1-infected patient. Renal function in this patient was partially recovered after atazanavir withdrawal and steroid therapy. Many reports have described atazanavir-associated urolithiasis, but this is the first case that describes chronic granulomatous nephropathy.

Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: Effects on long-term renal function after liver transplantation

BACKGROUND & AIMS The incidence of organic renal lesions in patients with end-stage liver disease is unknown. The goal of this study was to make a prospective evaluation of renal histological lesions in a group of unselected patients awaiting liver transplantation. METHODS Sixty cirrhotic patients underwent a renal biopsy via the transjugular route. The potential effect of renal lesions on renal function was evaluated five years after transplantation. RESULTS The yield of biopsies enabling satisfactory analysis was 77%, and no major complications occurred. Proteinuria>0.5 g/day was observed in only 8.7% of these patients, microscopic haematuria in 4.3%, creatinine levels>133 mmol/L (1.5mg/dl) in 10.9%, and Modification of the Diet in Renal Disease (MDRD) clearance<60 ml/min in 13.0%. Twenty-five patients (55.3%) had a morphological diagnosis of renal disease, 15 displayed IgA nephropathy and immunofluorescence testing showed that 12 had specific diabetic linear staining for IgG and albumin, of whom seven had associated histological lesions of diabetic nephropathy. Five years after liver transplantation, renal function had significantly deteriorated more in patients with initial diabetic lesions than in those with normal histology or IgA nephropathy alone. CONCLUSIONS In patients with end-stage liver disease, IgA nephropathy and diabetic lesions were frequently found despite the absence of renal impairment and/or urinalysis anomalies. Our results strongly suggest that severe renal failure develops preferentially in liver transplant recipients with diabetes or carbohydrate intolerance, and that pre-existing arterial lesions may favour the nephrotoxicity of calcineurin inhibitors. Diabetes prior to transplantation needs to be strictly managed and requires a renal sparing immunosuppressive regimen after transplantation.

Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.