EFFECTS AND INTERACTIONS OF GENTAMICIN, POLYASPARTIC ACID AND DIURETICS ON URINE CALCIUM-CONCENTRATION

Gentamicin causes isolated, reversible calciuria in rats by an unknown mechanism. We hypothesized that gentamicin calciuria is related to no nantibacterial properties that may interfere with transtubular calcium transport (calcium channel blockade, Na,K-ATPase inhibition or compet ition with calcium for binding to the brush-border membrane). The calc iuric effect of gentamicin was compared to the calcium channel blocker s lanthanum and cobalt, the Na,K-ATPase inhibitor ouabain and the poly cation aprotinin (which competes with gentamicin for brush-border memb rane binding). Although gentamicin 0.02 mmol/kg caused a 6-8-fold incr ease in urine calcium concentration, none of the other agents was calc iuric. We also found that the calciuric effects of gentamicin and furo semide were additive, whereas the noncalciuric diuretic chlorothiazide had no effect on gentamicin calciuria. We also determined the effect of poly-L-aspartic acid (PPA), which binds gentamicin and prevents nep hrotoxicity. PAA caused isolated calciuria similar in magnitude and ch aracter to gentamicin. However, PAA pretreatment decreased the magnitu de of gentamicin calciuria to insignificance. PAA pretreatment did not prevent furosemide calciuresis. These results indicate that: 1) genta micin and furosemide calciuria are caused by different mechanisms; 2) gentamicin calciuria is probably not mediated by calcium channel block ade, Na,K-ATPase inhibition or displacement of brush-border membrane-b ound calcium; 3) gentamicin and PAA calciuria may reflect interference with intracellular events related to transtubular calcium transport.