The Role of Leukotrienes in the Pathogenesis of Steroid-Sensitive Nephrotic Syndrome

The glomeruli are very sensitive to inflammatory injury. Many studies are currently being done on cytokines and inflammatory mediators in various types of renal diseases. The spectrum of known proinflammatory compounds originating from glomeruli has expanded recently to include arachidonic acid-derived lipoxygenase metabolites and platelet activating factor (PAF) (1, 2). In recent experimental studies, the leukotrienes from the arachidonic acid lipoxygenase pathway have been demonstrated to play an important role in inflammatory reactions in glomeruli after immune or nonimmune injuries (3-5). The biological effects of cysteinylleukotrienes (LTs) (LTC 4 , LTD 4 and LTE 4 ) on the kidneys include vasoconstriction, increase in arterial pressure, decrease in renal blood flow (RBF) and glomerular filtration rate (GFR), decrease in capillary pressure, proteinuria, ultrafiltration, oliguria, and mesangeal cell proliferation (4-7). LTC 4 causes epithelial cell proliferation and alters podocyte formation (8, 9). Nonpeptide LT (LTB 4 ), which is mostly released by endothelial cells, is a chemotactic factor for leukocytes. It mediates cell adhesion to endothelium and aggregation (6). Leukocytes and glomerular cells release PAF, Thromboxan A2, major basic protein (MBP), prostoglandins, hydroxyeicosatetraenoic acids (HETEs) and free radicals after activation by LTB 4 . LTB 4 increases the permeability of the glomerular basement membrane (GBM), causes proteinuria, and decreases RBF and GFR (7, 10, 11).