No abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by a hypercoagulable state related to persistently elevated levels of antiphospholipid antibodies (aPL). Current treatment for APS is only partially effective and new therapies are strongly needed. We report on a case of a 50 years old man with APS who suffered from recurrent thromboembolic episodes despite conventional anticoagulant treatment. Eight years after the first thrombotic manifestation he was diagnosed with a large B cell non-Hodgkin lymphoma. Treatment with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) plus rituximab was started with partial clinical remission of lymphoma and normalization of aPL levels with a three years follow-up period free of thrombotic episodes.A review of the literature revealed that only 12 case reports on the use of rituximab in patients with primary, secondary and catastrophic APS have been published. Current knowledge clearly suggests the need for clinical trials to evaluate the effect of rituximab in the treatment of resistant APS.

A new renal function test was developed based upon the pharmacologic effects of furosemide to quantify separately the rates of electrolyte and water reabsorption by different segments of the human nephron in vivo. Since furosemide impairs active NaCl transport to Henle's loop and the attendant hypertonicity of the interstitium, osmotic water reabsorption from collecting ducts decreases and the unreabsorbed volume is lost into the urine, causing a rise in flow rate. This volume is computed from the difference in urine flow rate during furosemide with respect to that previously measured during maximal water diuresis alone. Starting from this value, an appropriate set of equations allows the separate calculation of Na reabsorption by the loop of Henle and by the distal tubule. Studies to validate this hypothesis were performed by clearance techniques during maximal water diuresis in 58 normal controls, in 19 patients with liver cirrhosis and ascites, and in 11 patients with chronic renal failure. Measurements were performed before and after the intravenous administration of 50 mg furosemide. The quantitative measurements of segmental solute reabsorption in normal subjects were consistent with results obtained by different methods in man and experimental animals, fully validating this new method. In addition, the data allowed to establish that distal reabsorption is depressed because of reduced proximal delivery in cirrhosis, as a result of impaired transport along Henle's loop in chronic renal disease, while permeability of collecting ducts to water was normal in both conditions. Though still approximate, this new furosemide test represents a considerable improvement over current methods for measuring segmental transport by the human nephron.

Data from our cohort, one of the largest so far reported, add to the evidence that proinflammatory cytokines such as Interleukin-1, Interleukin-6, Interleukin-10 and tumor necrosis factor-α are important in SLE pathogenesis.

The treatment of membranoproliferative glomerulonephritis (MPGN) is considered by most authors as unrewarding, and the disease progresses to end-stage renal disease (ESRD). We studied the effectiveness of a new immunosuppressive (IS) regimen by analyzing the rates of remission, relapse and progression to ESRD in 19 patients with MPGN. The treatment consisted of 4 phases: (1) induction with intravenous boluses of methylprednisolone plus cyclophosphamide (CPM) orally; (2) maintenance with oral prednisone (PDN) in an alternateday regimen and CPM in a daily oral dose; (3) tapering during which PDN alone was slowly decreased; (4) discontinuation when CPM was omitted and PDN slowly withdrawn according to the steroid withdrawal schedule. At the end of the treatment that lasted on average 10 ± 1 months, 15 patients remitted, 3 improved and 1 progressed. There were 8 relapses in 6 patients: 4 in 3 patients were treated with repeat cycles and remitted completely. Four patients who had relapsed after 4, 8,11 and 13 years of remission refused retreatment and progressed rapidly to ESRD. All patients treated and retreated after relapsing had remissions, while renal failure and disease progression occurred in 1 patient only. Plasma creatinine averaged, in the whole group, 165 ± 26 before, 156 ± 30 after treatment and 224 ± 57 μM/1 at the end of 7.4 ± 0.8 years of follow-up. An intensive IS regimen combining steroids and alkylating agents in high doses and for a prolonged time is effective in inducing remission and halting progression to ESRD in patients with MPGN.