didanosine and Hypokalemia

Although adverse events in HIV patients taking tenofovir are relatively rare, postmarketing reports of nephrotoxicity have alerted physicians to other potentially serious outcomes. We present a series of 40 patients who developed hypokalemia associated with tenofovir. Identified risk factors included concomitant ritonavir or didanosine use, a lower weight and longer duration of tenofovir use. Recovery or improvement was seen in the majority of patients (66%) after the discontinuation of tenofovir; however, four deaths occurred. The associated consequences of tenofovir-related hypokalemia may be profound and life-threatening.

Topics: Adenine; Adolescent; Adult; Body Weight; Child; Didanosine; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Organophosphonates; Reverse Transcriptase Inhibitors; Risk Factors; Ritonavir; Tenofovir; Time Factors

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

Topics: Acute Kidney Injury; Animals; Anti-HIV Agents; Didanosine; Diet; Disease Models, Animal; HIV Infections; Hypokalemia; Magnesium; Male; Rats; Rats, Wistar; Risk Factors; Zidovudine

Topics: Didanosine; Humans; Hypokalemia