Use of rituximab as an induction therapy in anti-glomerular basement-membrane disease.

BACKGROUND: Anti-glomerular basement-membrane (anti-GBM) disease (or Goodpasture disease) is characterized by severe kidney and lung involvement. Prognoses have improved with treatments that combine plasma exchange and immunosuppressive drugs. However, patients with severe renal involvement can have poor renal outcomes and cyclophosphamide can cause significant complications. Anti-GBM antibodies have a direct pathogenic effect on the disease: thus, therapeutics that can decrease their production, such as rituximab, could be a good alternative. METHODS: The medical files of five patients that had received rituximab as a first-line therapy (instead of cyclophosphamide), plus plasma exchange and steroids, were reviewed. All patients had severe disease manifestations. RESULTS: Four patients required dialysis at diagnosis and remained dialysis-dependent over the mean follow-up of 15 months. Three patients had pulmonary involvement, but recovered even though mechanical ventilation was required. Anti-GBM antibodies became rapidly undetectable in all patients. One infectious and two hematological complications were observed. CONCLUSIONS: We report the outcomes of five patients with Goodpasture disease and treated with rituximab as a first-line treatment. This strategy was effective at treating pulmonary manifestations and was associated with a good biological response with no major serious adverse events. However, renal outcomes were not significantly improved.

Effect of double-filtration plasmapheresis for antibody-mediated rejection on hemostasis parameters and thrombin generation.

INTRODUCTION: Donor-specific alloantibodies (DSAs) cause kidney-allograft loss in chronic antibody-mediated rejection (CAMR). Treatment relies on blocking antibody-producing cells and removing DSAs by apheresis: e.g., double-filtration plasmapheresis (DFPP). MATERIALS AND METHODS: To determine the impact of DFPP (6 or 8 sessions/patient) on clotting factors and natural anticoagulants, and on thrombin generation, we performed a prospective and observational study in five CAMR kidney-transplant patients who received DFPP plus rituximab therapy. Thrombin generation was performed in poor platelet plasma (PPP) with 5 pM tissue factor without and with 2 nM recombinant human thrombomodulin. RESULTS: After the first DFPP session, median levels of high molecular-weight proteins (fibrinogen, FV, FVIII, FXI, FXIII, von Willebrand factors and α2-MG) decreased significantly to <50% of baseline values, whereas levels of low molecular-weight factors (<100 kDa) were not significantly modified, except for protein S and TFPI. Of note, binding-protein (BP) S, i.e., C4BP, was significantly decreased. Over the course of successive DFPP sessions, both high and lower molecular-weight proteins (<100 kDa) with longer half-lives (>2 days, prothrombin and factor XII) were significantly decreased. DFPP also highly affected thrombin generation in the absence of thrombomodulin but not significantly in the presence of thrombomodulin. After the first DFPP session, mean endogenous thrombin potential (ETP) and peak thrombin (PH) significantly decreased when the thrombin generation assay was performed without thrombomodulin (respectively, 1084 nM·min for ETP and 210 nM for PH after the first DFPP session compared to 1616 nM·min and 264 nM at baseline). In the presence of thrombomodulin, there was only a slight decrease in ETP and PH (respectively 748 nM·min, and 172 nM after the first DFPP session compared to 822 nM·min and 179 nM at baseline). After the last session, median ETP and PH decreased respectively to 646 nM·min and 143 nM without thrombomodulin, and, to 490 nM·min and 117 nM with thrombomodulin. CONCLUSIONS: DFPP significantly removed high molecular-weight proteins from the haemostatic system and profoundly decreased levels of protein S and TFPI. Overall thrombin-generation balance was only moderately affected in the presence of thrombomodulin. Nevertheless, high depletion of fibrinogen, FXIII and Von Willebrand Factor may expose patients to an increased risk of bleeding.

[Two cases of iatrogenic cutis and subcutis calcinosis after calcium-containing heparin injection]. / Calcinose cutanée et sous-cutanée après injection d'héparine calcique : à propos de deux cas.

BACKGROUND: Subcutis calcinosis, characterized by abnormal calcium deposition in the skin, is a rare side effect of calcium containing heparins. PATIENTS AND METHODS: Two patients with renal failure presented skin lesions after receiving a calcium-containing heparin treatment. The first patient exhibited erythematous nodules on the abdomen and the second a large erythematous induration of the abdomen and nodules on the thighs. Both had normal blood analysis. The diagnosis of subcutis calcinosis was confirmed by the histological exam showing calcium deposit in the dermis and hypodermis. Outcome was unfavourable in one of the patients who developed a superinfection and skin necrosis lesion requiring surgery at 2 months. DISCUSSION: Subcutis calcinosis is a rare and probably underdiagnosed disease. To our knowledge, only 10 cases have been reported. The pathogenesis is not well-known, tissue damage and calcium disorders are considered as risk factors. The differential diagnoses that can be suspected include calciphylaxis, such as calcifying panniculitis and other local side effects of heparins. Outcome is usually favourable without treatment. CONCLUSION: We describe two cases of iatrogenic subcutis calcinosis after injections of calcium-containing heparins, including the second case of poor outcome. Clinicians should be aware of this adverse effect since other heparins such as fondaparinux or low-weight molecular heparins are contraindicated in patients with renal failure, leading to a large prescription of calcium-containing heparins in this population.

[Indications of central venous access in the context of acute renal insufficiency]. / Indications des accès veineux centraux dans le contexte de l'insuffisance rénale aiguë.

Central vascular access indications in acute renal failure have never been precised by clinical studies. This is probably due to the epidemiology of acute renal failure and to heterogeneity of acute renal failure patients. Schematically, acute renal failure can be divided into three groups of increasing gravity: isolated non complicated acute renal failure, complicated acute renal failure, and severe acute renal failure that arises in the setting of multiple organ failure syndrome. Central vascular access indications, such as catheters type and vascular sites of insertion are actually based on many clinical and technical considerations. These considerations include the gravity of acute renal failure, the need of emergency extracorporeal renal replacement therapy, the modalities of such therapy, and the expected catheterism duration.

CD4 lymphocytopenia as a risk factor for skin cancers in renal transplant recipients.

BACKGROUND: Renal transplant recipients are at increased risk of developing skin cancer. It remains difficult to establish the actual influence of overimmunosuppression in the development of skin cancers. We investigated whether lymphocyte subset count may predict the risk of developing skin cancer in long-term renal transplant recipients. METHODS: One hundred fifty long-term renal transplant recipients were followed for a mean period of 26 months. Each patient was examined at least annually by a dermatologist. Lymphocyte subsets were measured annually. RESULTS: Fifteen patients exhibited skin cancers. Patients with and without skin cancer did not differ in age, gender, transplant duration, hemodialysis duration before transplantation, immunosuppressive regimen, and serum creatinine concentration. CD4 cell counts were significantly lower in patients with skin cancers (330+/-179/mm3 vs. 503+/-338/mm3; P<0.01), whereas total lymphocyte and CD8 and CD19 cell counts were similar between the two groups. CONCLUSIONS: CD4 cell depletion is associated with skin cancer in long-term renal transplant recipients.