Urinary eicosanoids and the assessment of glomerular inflammation.
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.
Lefkowith
J B
JB
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Pippin
J
J
Nagamatsu
T
T
Lee
V
V
D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism / Q000652:urine*; D005921:Glomerulonephritis / Q000378:metabolism / Q000652:urine*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism / Q000652:urine; D010477:Perfusion; D051381:Rats; D011917:Rats, Inbred Lew; D013931:Thromboxanes / Q000378:metabolism / Q000652:urine
D015415:Biomarkers; D015777:Eicosanoids; D013931:Thromboxanes; D007975:Leukotriene B4