Vascular hyperpermeability in nephrotic edema

Background/Aim: There is increasing evidence that hypoalbuminemia and the i nability of the renal distal tubule to excrete salt are not the only factor s responsible for nephrotic edema. We tested the possibility that vascular hyperpermeability also plays a role in the pathophysiology of nephrotic ede ma in human primary glomerulonephritis. Methods: We investigated the capill ary permeability by means df a standardized test using albumin labelled wit h technetium (Tc-99m-albumin) in 20 healthy adults and in 101 nephrotic adu lt patients comprising 60 patients with idiopathic nephrotic syndrome (INS; minimal-change nephropathy and segmental glomerulosclerosis), 32 with idio pathic membranous nephropathy (IMN) and 9 patients with idiopathic type mem branoproliferative glomerulonephritis (MPGN). The patients and healthy cont rols were also compared with a group of women (n = 25) with idiopathic cycl ic edema, a disease in which an increase in capillary permeability plays a pivotal role. The capillary permeability measured by the Landis isotope tes t is normal in edematous patients with cardiac and renal impairment unrelat ed to glomerular disease, cirrhosis, hypothyroidism, lymphatic obstruction and diuretic abuse. As values were not normally distributed, nonparametric analysis of variance was used (Kruskal-Wallis test), and patient groups wer e compared with healthy controls and with women with idiopathic cyclic edem a by means of the two-tailed nonparametric Mann-Whitney test. The effects o f high-dose steroids and Ginkgo biloba extract (Tanakan(R); an agent able t o improve capillary permeability) were analyzed by means of the two-tailed nonparametric Wilcoxon test. Results: The capillary permeability was signif icantly increased (Mann-Whitney test) in each glomerular disease group comp ared with the healthy controls. Tc-99m-albumin extravasation values (%; med ian and range in parentheses were the following: healthy controls 0 (0-8.4) ; idiopathic cyclic edema patients 11.5 (8-24), p < 0.001; INS 20 (0-50), p < 0.0001; IMN 12.5 (0-40), p < 0.001, and MPGN 10 (0-40), p < 0.05. An inc rease in capillary permeability exceeding the upper limit of control values (> 8% of Tc-99m-albumin extravasation) was observed in 88% of INS, in 53% of IMN and in 44% of MPGN patients. The increase in capillary permeability (%) was greater in idiopathic nephrotic patients than in idiopathic cyclic edema patients (p < 0.005, Mann-Whitney test) and was markedly reduced in n ephrotic patients receiving high-dose steroids (n = 8) [before 25 (8-40); a fter 0 (0-25), p < 0.005 (Wilcoxon's test)] and high doses of G. biloba ext ract (n = 16) [before 30 (8-50); after 2.5 (0-20, p < 0.0005 (Wilcoxon's te st)]. Conclusions: We conclude that capillary permeability is severely alte red in most of the nephrotic patients with primary glomerulonephritis. Thes e results strongly suggest that the capillary hyperpermeability plays a rol e in the pathophysiology of nephrotic edema in primary glomerular disease, especially in INS. We postulate that this widespread abnormality in capilla ry permeability is related to the release of vascular permeability factor a nd other cytokines by immune cells. Copyright (C) 2000 S. Karger AG, Basel.