Nephrotoxic
nephritis, a model system for
glomerulonephritis, is characterized by glomerular
inflammation,
proteinuria, and a marked increase in ex vivo glomerular
eicosanoid production. This study addressed whether urinary
eicosanoids might serve as noninvasive markers for glomerular
inflammation and damage with nephrotoxic
nephritis and its accelerated variant. Accelerated
nephritis, relative to simple
nephritis, was characterized by more substantial glomerular
inflammation, particularly that due to neutrophils. Correspondingly, accelerated
nephritis was accompanied by greater
proteinuria and more marked elevations in glomerular
eicosanoids generated ex vivo. With respect to urinary
eicosanoids,
thromboxane, but not
leukotriene B4, was detected in the urine of normal animals. After the induction of nephrotoxic
nephritis, urinary
thromboxane was moderately elevated (twofold) and urinary
leukotriene B4 was variably present (three of seven animals). In accelerated
nephritis, urinary
thromboxane was more markedly elevated (sixfold) and
leukotriene B4 was consistently present. The presence of urinary
leukotriene B4 was confirmed by gas chromatography/mass spectrometry. Urinary
eicosanoids together correlated with glomerular leukocyte numbers and
proteinuria by linear regression. Urinary
leukotriene B4 individually correlated with glomerular neutrophil numbers. Renal metabolism of
leukotriene B4 to omega oxidation products by the rat kidney was not apparent. These data validate that the enhanced glomerular
eicosanoid metabolism seen in nephrotoxic
nephritis takes place in vivo and additionally suggest that both urinary
thromboxane and
leukotriene B4 may serve as noninvasive markers for glomerular
inflammation and damage. In light of these and prior studies, urinary
thromboxane may be a general marker of glomerular
inflammation and
leukotriene B4 may be a more specific index of acute
inflammation.