Cyclosporin A in steroid-sensitive nephrotic syndrome with frequent relapses.

Eight patients with steroid-sensitive nephrotic syndrome which frequently relapsed despite cyclophosphamide treatment were given cyclosporin A (7.5 mg/kg/day to 10 mg/kg/day) for 8 to 12 weeks. Six had minimal change glomerulonephritis and two had focal segmental glomerulonephritis. Cyclosporin A was given to 5 patients when their nephrotic syndrome was in relapse and to 3 patients when the nephrotic syndrome was in remission. Cyclosporin A induced a transient remission in only one patient

Failure to induce anti-glomerular basement membrane glomerulonephritis in TNFα/β deficient mice

TNF is a key proinflammatory cytokine playing a central role in the expression of endothelial adhesion molecules required for the recruitment of inflammatory cells. Proliferative glomerulonephritis induced by anti-GBM antibody is characterized by the recruitment of inflammatory cells into the glomerulus and capillary damage followed by regeneration with crescent formation. The glomerular pathology may be due to TNF induction and we therefore tested this hypothesis in TNFα/β deficient mice. Anti-GBM antibody administration in sensitised wild-type mice resulted in deposition of immune complexes and complement factor 3, followed by increased ICAM-1 and VCAM-1 expression and influx of polymorphonucelar leucocytes. Distinct proteinuria precedes proliferative glomerulonephritis with glomerular crescent formation, which is fully developed at 10 days. By contrast, no glomerulonephritis developed in TNFα/β deficient mice. Comparable antibody complex deposits are found, but the upregulation of ICAM-1 and VCAM-1, the influx of inflammatory cells and the subsequent tissue damage is absent in TNFα/β deficient mice. Therefore, we conclude that TNF plays a key role for the recruitment of inflammatory cells by preventing the upregulation of endothelial adhesion molecule and the subsequent development of proliferative glomerulonephritis

Urinary tissue factor in glomerulonephritis: a potential marker of glomerular injury?

AIM: To investigate the significance of urinary tissue factor (uTF) concentrations in patients with glomerulonephritis. METHODS: Urine samples were collected from normal subjects (n = 57), patients with uncomplicated renal stones (n = 30), and patients with glomerulonephritis (n = 150). Samples were then centrifuged and the pellets solubilised in n-octyl-beta-glucopyranoside. uTF concentrations were determined using a one stage kinetic chromogenic assay. RESULTS: The uTF concentration was higher in patients with glomerulonephritis than in normal controls (p < 0.01) or in patients with renal stones (p < 0.05). uTF activity correlated with the protein creatinine index (PCI, r = 0.41, p < 0.001) and seven patients with glomerulonephritis and a PCI < or = 0.1 g/mmol had raised uTF. Glomerulonephritis patients were subdivided into two groups depending on the PCI: < 0.2 g/mmol creatinine (mild to moderate proteinuria, group I) and > or = 0.2 g/mmol creatinine (heavy proteinuria, group II). In group I, uTF concentrations were higher in patients with either immune complex (IC) glomerulonephritis (p < 0.01) or non-IC (p < 0.05) glomerulonephritis than in normal controls. In group II, the IC glomerulonephritis group had higher uTF concentrations than normal controls (p < 0.001) or patients with renal stones (p < 0.01); and non-IC glomerulonephritis patients had higher uTF than normal controls (p < 0.01). When the glomerulonephritis groups were divided into broad WHO subtypes, the significance level varied with the type of glomerulonephritis. CONCLUSIONS: uTF is increased in patients with glomerulonephritis, and its concentration may reflect the aetiopathogenesis of glomerulonephritis