Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive agents alter proteinuria by modulating glomerular hemodynamics. The authors hypothesized that vasoactive agents may be altering degradation of the collagen component of glomerular basement membrane, which also may be contributing to proteinuria. Mesangial cells treated with 10(-6) M angiotensin II had higher (P < 0.01) metalloproteinase activity (MA) when compared with control cells. This effect of angiotensin II was dose dependent. Amlodipine (10(-6) M), a calcium channel blocker, inhibited MA (control, 5.86 +/- 0.08 microgram versus 4.13 +/- 0.06 microgram gelatin degraded/mg protein, P < 0.001). The decrease in mesangial MA caused by amlodipine also occurred in a dose dependent manner. Amlodipine attenuated (P < 0.05) angiotensin II-stimulated MA (control, 6.69 +/- 0.30 micrograms, angiotensin II, 10.68 +/- 0.49 micrograms, angiotensin II+amlodipine 8.29 +/- 0.30 micrograms gelatin degraded/mg protein). Prostaglandin E2 increased (P < 0.001) MA (control, 10.22 +/- 0.9 micrograms versus prostaglandin E2, 17.9 +/- 0.9 micrograms gelatin degraded/mg protein), whereas indomethacin, a prostaglandin inhibitor, attenuated the metalloproteinase activity (control, 9.67 +/- 0.32 micrograms vs. 10(-6) M indomethacin, 4.22 +/- 0.31 micrograms gelatin degraded/mg protein, P < 0.001). Indomethacin also inhibited angiotensin II-stimulated MA (angiotensin II, 18.66 +/- 0.46 vs. angiotensin II+indomethacin, 11.86 +/- 0.56 micrograms degraded/mg protein, P < 0.001). Similarly, meclofenamate, another prostaglandin inhibitor, attenuated (P < 0.001) angiotensin II-induced MA. Because angiotensin II increases prostaglandin E2 synthesis by mesangial cells, it appears that increased MA, induced by angiotensin II, may be mediated partly through the generation of prostaglandin E2.
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PMID:Vasoactive agents modulate matrix metalloproteinase-2 activity by mesangial cells. 750 3

The effects of indomethacin on urinary protein excretion, levels of serum albumin and renal function were studied prospectively in six patients with systemic lupus erythematosus (SLE) and refractory nephrotic syndrome due to lupus nephritis. Two had membranoproliferative glomerulonephritis, two had diffuse proliferative glomerulonephritis, and one each had mesangioproliferative and membranous glomerulonephritis. All experienced a considerable reduction in urinary protein excretion and an increase in serum albumin. Indomethacin was discontinued in two patients because of side effects, and proteinuria recurred to pretreatment levels. The decrease of proteinuria continued during long-term treatment in three patients. Indomethacin did not cause a permanent decline in renal function. Our results suggest that therapy with indomethacin may be beneficial for the treatment of refractory nephrotic syndrome in selected SLE patients. However, because of potential side effects the administration of indomethacin should be monitored closely.
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PMID:Refractory nephrotic syndrome in lupus nephritis: favorable response to indomethacin therapy. 848 64


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