Effects of hypokalemia and hypomagnesemia on zidovudine (AZT) and didanosine (ddI) nephrotoxicity in rats.
BACKGROUND
Zidovudine (AZT) and didanosine (ddI) are antiretroviral drugs widely used in AIDS patients. Hypokalemia and hypomagnesemia are frequently encountered in AIDS patients using AZT and/or ddI.


OBJECTIVE
To verify the effects of AZT and ddI on rat renal function submitted to normal diet, low potassium diet and magnesium-free diet.


METHODS
Glomerular filtration rate and renal hemodynamic were measured in Wistar rats submitted to a normal or a potassium-depleted diet. The animals were given AZT, ddI for 15 days. Six groups of rats were studied: normal diet, normal diet + AZT, normal diet + ddI, low K diet, low K diet + AZT and low K diet + ddI. Three additional groups of rats submitted to magnesium depletion for 15 days were also studied: magnesium-free diet, magnesium-free diet + AZT and magnesium-free diet + ddI.


RESULTS
AZT and didanosine did not modify renal function of rats on a normal diet. However, in hypokalemic rats, both drugs produced a decrease in glomerular filtration rate and in renal blood flow consequent to renal vasoconstriction and associated with alterations in tubular function (characterized by an increased fractional excretion of sodium). Hypomagnesemia induced a decrease in glomerular filtration rate and in renal blood flow only in AZT-treated rats.


CONCLUSIONS
Our data suggest that hypokalemia predisposes to AZT and ddI nephrotoxicity, while hypomagnesemia predisposes only to AZT nephrotoxicity. Thus, chronic AZT and ddI administration may produce acute renal failure in AIDS patients with hypokalemia and/or hypomagnesemia. Serum K and Mg levels should be carefully monitored in these patients.
Seguro
A C
AC
Faculdade de Medicina da Universidade de São Paulo, LIM-12, São Paulo, Brazil. trulu@usp.br
de Araujo
M
M
Seguro
F S
FS
Rienzo
M
M
Magaldi
A J
AJ
Campos
S B
SB
D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects*; D016049:Didanosine / Q000009:adverse effects* / Q000627:therapeutic use; D004032:Diet; D004195:Disease Models, Animal; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D007008:Hypokalemia / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D008274:Magnesium / Q000009:adverse effects* / Q000097:blood*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine; D008274:Magnesium; D016049:Didanosine