Foscarnet nephrotoxicity: mechanism, incidence and prevention.
Foscarnet is a pyrophosphate analogue that has been successfully used in severe cytomegalovirus (CMV) infections. Little is known of the incidence and mechanisms of foscarnet-induced nephrotoxicity as most data comes from recipients of renal allografts or from patients with severe underlying disease or with other nephrotoxic drugs. We have retrospectively analyzed the evolution of renal function after 56 courses of foscarnet. In addition, we have prospectively studied the protective effects of hydration on foscarnet nephrotoxicity (2.5 liters of saline/day during the night before the foscarnet therapy and throughout the course of treatment). Foscarnet-induced acute renal failure was defined as a rise in serum creatinine of at least 25% from the basal value. An increase in serum creatinine occurred in 37 cases out of the 56 courses of foscarnet (66%). The mean serum creatinine prior to foscarnet was 80.5 +/- 3.3 mumol/l and the mean increase was 190 +/- 28.3 mumol/l (range 80-1,000). Peak serum creatinine was higher than 200 and 300 mumol/l in 16 and 13 patients, respectively. Kidney obtained at autopsy from a 30-year-old male with AIDS, CMV pneumonitis and acute renal failure secondary to foscarnet administration showed an extensive tubular necrosis. In the group which was prospectively hydrated only 1 patient had an acute renal failure. The mean serum creatinine at the peak (96 +/- 4 mumol/l) and at the end of the treatment (83 +/- 4 mumol/l) was significantly lower (p less than 0.05) than in non hydrated patients. In conclusion, foscarnet is a highly nephrotoxic drug which induces acute tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Deray
G
G
Department of Nephrology, Hôpital Pitié-Salpêtrière, Paris, France.
Martinez
F
F
Katlama
C
C
Levaltier
B
B
Beaufils
H
H
Danis
M
M
Rozenheim
M
M
Baumelou
A
A
Dohin
E
E
Gentilini
M
M
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D005440:Fluid Therapy; D017245:Foscarnet; D006801:Humans; D008297:Male; D008875:Middle Aged; D010746:Phosphonoacetic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D012189:Retrospective Studies
D017245:Foscarnet; D003404:Creatinine; D010746:Phosphonoacetic Acid