Effects of dietary electrolyte supplementation on gentamicin nephrotoxicity.
The effects of electrolyte supplementation via drinking solutions on gentamicin-induced nephrotoxicity were studied in rats. Four groups of animals were injected with gentamicin, 120 mg/kg daily for 5 days and were studied 2-4 days after the last injection. Electrolyte supplements were begun before the gentamicin injections and were continued throughout the study. The drinking solutions were tap water, NaCl, NaCl + KCl, or NaHCO3 + KHCO3 + diamox. At the end of the study, blood urea nitrogen (BUN) and serum creatinine were markedly increased only in the group receiving tap water. Nevertheless, 24 hour creatinine clearance in awake rats and inulin clearance in anesthetized rats were found to be severely reduced in all gentamicin-treated animals. However, the rats receiving NaHCO3 + KHCO3 + diamox had significantly higher creatinine clearance than all other experimental groups. Proximal intratubular free-flow pressure, measured by micropuncture, and internal proximal diameters were significantly increased above normal controls in all groups, but were least abnormal in the rats receiving HCO3- and diamox. Semiquantitative histologic evaluation revealed significantly less tubular necrosis and cast formation in this group than in all the other experimental groups. The observations suggest that dietary sodium, potassium, and chloride supplements, even accompanied by large fluid intake, provide relatively little protection against gentamicin nephrotoxicity. In contrast, HCO3- and diamox supplements resulted in significant, albeit incomplete, protection of GFR and renal histology.
Aynedjian
H S
HS
Department of Medicine, Montefiore Medical Center, Bronx, NY 10467.
Nguyen
D
D
Lee
H Y
HY
Sablay
L B
LB
Bank
N
N
D000818:Animals; D004032:Diet; D004326:Drinking; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004573:Electrolytes / Q000008:administration & dosage*; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012996:Solutions
D004573:Electrolytes; D005839:Gentamicins; D012996:Solutions