Laboratory Investigation

Kidney International (1987) 32, 198–203; doi:10.1038/ki.1987.192

Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients

Masayasu Inoue, Kenji Okajima, Kazunobu Itoh, Yukio Ando, Nobukazu Watanabe, Tatsuomi Yasaka, Sumi Nagase and Yoshimasa Morino

Departments of Biochemistry and of Medicine, Kumamoto University Medical School, 2-2-1, Honjo, Kumamoto 860; Department of Medicine, Kohseikan Hospital, Saga City, Saga; and Department of Chemistry, Sasaki Institute, 2-2 Kanda, Chiyodaku, Tokyo, Japan.

Correspondence: Dr M Inoue, Department of Biochemistry, Kumamoto University Medical School, 2-2-1, Honjo, Kumamoto 860, Japan.

Received 15 September 1986; Revised 3 March 1987.

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Abstract

Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients. To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of this diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis.

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