ELEVATED CYSTEINYL LEUKOTRIENE EXCRETION IN EXPERIMENTAL GLOMERULONEPHRITIS

The involvement of cysteinyl leukotrienes (LT) in the etiology of glom erulonephritis (GN) was investigated in a rat model of nephrotoxic ser um nephritis in which renal function, morphology, LTC(4) synthase acti vity and urinary cysteinyl LT excretion were monitored over seven days . Significant alterations in renal function and morphology were eviden t on day 1 in nephritic rats, with a 12% decline in creatinine clearan ce, a greater than three-fold increase in urinary protein excretion an d histologic evidence of basement membrane thickening. Urinary LTC(4) excretion in the nephritic rats was elevated at this time to 140 +/- 3 8 pg/hr (P < 0.01) compared to undetectable levels in control animals. On days 3 and 7, while proteinuria intensified and glomerular filtrat ion remained depressed, LTC(4) excretion declined 14% (NS) and 79% (P < 0.05), respectively. The temporal changes in urinary LTC(4) excretio n were paralleled by concomitant alterations in LTC(4) synthase activi ty in renal cortical microsomes, where an 84% (P < 0.01) drop in enzym e activity occurred from day 1 to day 7 in the nephritic group. This d ata provides the first measurement of urinary cysteinyl LT excretion a nd altered LTC(4) synthase activity in a model of experimental GN and supports an early role for LT's in the development of subsequent funct ional changes.