Background. Immunoglobulin A nephropathy (IgAN) is the most common cause of chronic renal failure among primary glomerulonephritis patients. The best treatment for IgAN remains poorly defined. We planned a long-term, prospective, open-label, multicentre, centrally randomized controlled trial to assess whether the combination of prednisone and ramipril was more effective than ramipril alone in patients with proteinuric IgAN.

There is not agreement about the best maintenance treatment for patients with diffuse lupus nephritis. This multicenter, randomized trial compared the safety and efficacy of cyclosporine and azathioprine. Seventy-five patients with diffuse proliferative lupus were given three intravenous methylprednisolone pulses followed by prednisone and oral cyclophosphamide for a median of 90 d. Subsequently, patients were randomly assigned either to cyclosporine or to azathioprine for 2 yr (core study). Treatment continued for up to 4 yr (follow-up study). The primary outcome measure was the incidence of disease flares. Secondary end points were proteinuria per day, creatinine clearance, and adverse effects. Seven flares occurred in the cyclosporine group, and eight occurred in the azathioprine group. At the end of the core study, mean proteinuria decreased from 2.8 ± 3.57 to 0.4 ± 0.85 g/d (P < 0.0001) in the cyclosporine group and from 2.2 ± 1.94 to 0.5 ± 0.78 g/d (P < 0.0002) in the azathioprine group. After 4 yr, mean proteinuria was 0.2 ± 0.24 and 0.3 ± 0.33 g/d, respectively. At the core study end and at the follow-up completion, creatinine clearance and BP levels did not change significantly from baseline in either group. Five of 36 patients who were receiving cyclosporine and four of the 33 who were receiving azathioprine stopped the treatment because of adverse effects. For patients with diffuse proliferative lupus nephritis, azathioprine or cyclosporine combined with corticosteroids demonstrated equal efficacy in the prevention of flares.

Membranoproliferative glomerulonephritis (MPGN) may be a component of a generalized vasculitis as well as a component of the clinical expression of type-II mixed cryoglobulinemia (MC). Several studies have established a striking association between hepatitis C virus (HCV) infection and MC. The potential role of HCV in the pathogenesis of MPGN, which occurs in almost half of the cases of MC patients, has not been fully investigated, and the demonstration of HCV proteins as the antigenic constituent of the glomerular immune deposits has remained elusive. Kidney biopsy specimens were obtained from 12 HCV RNA, antibody to HCV (anti-HCV)-positive patients with MPGN and type-II MC, and from 8 controls (3 HCV RNA, anti-HCV-negative patients with MPGN and MC and 5 with noncryoglobulinemic “idiopathic” MPGN). Murine monoclonal antibodies developed against c22-3, E2/NS1, c33c, c100-3, and NS5 proteins were used to detect HCV-related antigens by indirect immunohistochemistry. Acid electroelution of tissue sections was performed to enhance the sensitivity of the immunohistochemical method. Specific HCV-related proteins were detected in glomerular and tubulo-interstitial vascular structures in 8 (66.7%) HCV-positive MC patients and in none of the HCV RNA, anti-HCV-negative controls. HCV immunoreactive deposits displayed the following two major patterns: 1) a linear, homogeneous deposition along glomerular capillary walls, including endothelial cells and sub-endothelial spaces; and 2) a granular bead-like appearance with distinct deposits in mesangial and paramesangial cells. Immunoglobulin G (IgG) and M (IgM) and C3 fraction deposition in adjacent kidney sections displayed features comparable with those found for HCV deposits. Patients with granular deposits showed more pronounced renal impairment and severe proteinuria. These findings indicate that in MC patients with HCV-associated MPGN, kidney deposits consist of HCV-containing immune complexes that are likely to play a direct pathogenetic role in the renal damage.