Drug-induced changes in renal hippurate clearance as a measure of renal blood flow.
We studied the accuracy of the plasma 131I-hippurate clearance technique to monitor drug-induced changes in renal blood flow (RBF) by comparing it to a flow probe technique in six conscious, chronically instrumented dogs. Placebo caused no change in RBF, either established by hippurate clearance (ERPFhip) or by renal blood flow probe (RBFprobe). Enalaprilate induced a rise in ERPFhip and RBFprobe (+26 +/- 5 and 44 +/- 12%), as did dopamine (+16 +/- 4 and +33 +/- 5%). Intravenous infusion of norepinephrine induced a rise in ERPFhip (+2 +/- 6%, NS) and in RBFprobe (+18 +/- 3%), as did nitroprusside (+14 +/- 4% and +13 +/- 6%, NS). Indomethacin induced a fall in ERPFhip (-8 +/- 2%) and in RBFprobe (-7 +/- 3%, NS), as did angiotensin II (-19 +/- 1 and -26 +/- 3%). Renal hippurate extraction (Ehip) was affected by enalaprilate, dopamine, and angiotensin II (-5 +/- 2, -7 +/- 1, and +5 +/- 2%, respectively). Hematocrit (Hct) was affected by dopamine, norepinephrine, and nitroprusside (+2 +/- 1, +6 +/- 1, and -6 +/- 2%, respectively). Drug-induced changes in ERPFhip correlated well with changes in RBFprobe (r = 0.902, P < 0.01). Changes in Ehip did not independently affect this relation, whereas changes in Hct did: delta RBF(% of baseline) = 1.529 x delta ERPFhip(% of baseline) + 1.296 x delta Hct(% of baseline). These data indicate that drug-induced changes in plasma hippurate clearance can, even when changes in renal hippurate extraction are unknown, be used as a reliable indicator of changes in renal blood flow if changes in hematocrit are taken into account.
Groningen Institute for Drug Studies (GIDS), Department of Medicine, University Hospital, The Netherlands.
C A
CA
Visscher
D
D
de Zeeuw
P E
PE
de Jong
W J
WJ
Sluiter
R M
RM
Huisman
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006400:Hematocrit; D006626:Hippurates / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012044:Regression Analysis; D012079:Renal Circulation; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects
D006626:Hippurates; C030514:hippuric acid