Reversal of trimethoprim-induced antikaliuresis.
High-dose trimethoprim-sulfamethoxazole (TMP-SMX) causes hyperkalemia, thought to result from TMP-induced blockade of amiloride-sensitive Na(+)-channels in the distal nephron. The present study was performed in anesthetized dogs to determine if increasing distal sodium delivery affects this antikaliuretic effect. In Group 1, intrarenal infusion of vehicle did not alter renal function. In Group 2, i.v. infusion of amiloride led to diuresis, natriuresis and antikaliuresis associated with a reduction of the transtubular potassium gradient (TTKG) in both kidneys. Intrarenal infusion of TMP (0.2 mg/kg/min) into the left kidney did not further alter these parameters. In groups 3 and 4, intrarenal infusion of TMP caused an ipsilateral diuresis, natriuresis, antikaliuresis and a reduction in (TTKG) without affecting the contralateral kidney. The TMP infusion was followed by furosemide (20 mg i.v.) in group 3 and acute saline loading in group 4. Despite continuous TMP infusion, both furosemide and saline loading reversed the antikaliuretic effect of TMP in the ipsilateral kidney and was associated with a similar kaliuresis, diuresis, natriuresis and decrease in urine osmolality in both kidneys. The TTKG following furosemide or saline loading increased in the ipsilateral kidney and decreased in the contralateral kidney. In all groups the systemic and renal hemodynamics remained unchanged. These results suggest that acute administration of TMP inhibits the amiloride-sensitive Na(+)-channel and K+ secretion in the distal nephron. Maneuvers that increase distal Na+ delivery can abrogate TMP's antikaliuretic effect due, in part, to an increase of the low TTKG observed with TMP.
Reiser
I W
IW
Division of Nephrology and Hypertension, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA.
Chou
S Y
SY
Brown
M I
MI
Porush
J G
JG
D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006947:Hyperkalemia / Q000139:chemically induced / Q000517:prevention & control; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D011188:Potassium / Q000652:urine*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D026941:Sodium Channel Blockers; D014295:Trimethoprim / Q000633:toxicity*
D000892:Anti-Infective Agents, Urinary; D026941:Sodium Channel Blockers; D005665:Furosemide; D012964:Sodium; D014295:Trimethoprim; D011188:Potassium