Mechanism of hypoalbuminemia in rodents

M. Koltun, J. Nikolovski, Kimberley Strong, D. Nikolic-Paterson, W.D. Comper

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    Normal albumin loss from the plasma is thought to be minimized by a number of mechanisms, including charge repulsion with the capillary wall and an intracellular rescue pathway involving the major histocompatibility complex-related Fc receptor (FcRn)-mediated mechanism. This study investigates how these factors may influence the mechanism of hypoalbuminemia. Hypoalbuminemia in rats was induced by treatment with puromycin aminonucleoside (PA). To test the effects of PA on capillary wall permeability, plasma elimination rates were determined for tritium-labeled tracers of different-sized Ficolls, negatively charged Ficolls, and 14C-labeled tracer of albumin in control and PA-treated Sprague-Dawley rats. Urinary excretion and tissue uptake were also measured. Hypoalbuminemia was also examined in two strains of FcRn-deficient mice: 2-microglobulin ( 2M) knockout (KO) mice and FcRn α-chain KO mice. The excretion rates of albumin and albumin-derived fragments were measured. PA-induced hypoalbuminemia was associated with a 2.5-fold increase in the plasma elimination rate of albumin. This increase could be completely accounted for by the increase in urinary albumin excretion. Changes in the permeability of the capillary wall were not apparent, inasmuch as there was no comparable increase in the plasma elimination rate of 36- to 85-Å Ficoll or negatively charged 50- to 80-Å Ficoll. In contrast, hypoalbuminemic states in 2M and FcRn KO mice were associated with decreases in excretion of albumin and albumin-derived fragments. This demonstrates that the mechanism of hypoalbuminemia consists of at least two distinct forms: one specifically associated with the renal handling of albumin and the other mediated by systemic processes.
    Original languageEnglish
    Pages (from-to)H1604-H1610
    JournalAmerican Journal of Physiology: Heart and Circulatory Physiology
    Volume288
    Issue number4
    DOIs
    Publication statusPublished - 2005

    Fingerprint

    Hypoalbuminemia
    Albumins
    Rodentia
    Puromycin Aminonucleoside
    Ficoll
    Knockout Mice
    Capillary Permeability
    Tritium
    Fc Receptors
    Major Histocompatibility Complex
    Serum Albumin
    Sprague Dawley Rats
    Kidney

    Cite this

    Koltun, M. ; Nikolovski, J. ; Strong, Kimberley ; Nikolic-Paterson, D. ; Comper, W.D. / Mechanism of hypoalbuminemia in rodents. In: American Journal of Physiology: Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 4. pp. H1604-H1610.
    @article{963771d5d1ad48588c248d0fc89233e4,
    title = "Mechanism of hypoalbuminemia in rodents",
    abstract = "Normal albumin loss from the plasma is thought to be minimized by a number of mechanisms, including charge repulsion with the capillary wall and an intracellular rescue pathway involving the major histocompatibility complex-related Fc receptor (FcRn)-mediated mechanism. This study investigates how these factors may influence the mechanism of hypoalbuminemia. Hypoalbuminemia in rats was induced by treatment with puromycin aminonucleoside (PA). To test the effects of PA on capillary wall permeability, plasma elimination rates were determined for tritium-labeled tracers of different-sized Ficolls, negatively charged Ficolls, and 14C-labeled tracer of albumin in control and PA-treated Sprague-Dawley rats. Urinary excretion and tissue uptake were also measured. Hypoalbuminemia was also examined in two strains of FcRn-deficient mice: 2-microglobulin ( 2M) knockout (KO) mice and FcRn α-chain KO mice. The excretion rates of albumin and albumin-derived fragments were measured. PA-induced hypoalbuminemia was associated with a 2.5-fold increase in the plasma elimination rate of albumin. This increase could be completely accounted for by the increase in urinary albumin excretion. Changes in the permeability of the capillary wall were not apparent, inasmuch as there was no comparable increase in the plasma elimination rate of 36- to 85-{\AA} Ficoll or negatively charged 50- to 80-{\AA} Ficoll. In contrast, hypoalbuminemic states in 2M and FcRn KO mice were associated with decreases in excretion of albumin and albumin-derived fragments. This demonstrates that the mechanism of hypoalbuminemia consists of at least two distinct forms: one specifically associated with the renal handling of albumin and the other mediated by systemic processes.",
    author = "M. Koltun and J. Nikolovski and Kimberley Strong and D. Nikolic-Paterson and W.D. Comper",
    year = "2005",
    doi = "10.1152/ajpheart.00808.2004",
    language = "English",
    volume = "288",
    pages = "H1604--H1610",
    journal = "American Journal of Phsyiology - Heart and Circulatory Physiology",
    issn = "0363-6135",
    publisher = "American Physiological Society",
    number = "4",

    }

    Mechanism of hypoalbuminemia in rodents. / Koltun, M.; Nikolovski, J.; Strong, Kimberley; Nikolic-Paterson, D.; Comper, W.D.

    In: American Journal of Physiology: Heart and Circulatory Physiology, Vol. 288, No. 4, 2005, p. H1604-H1610.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Mechanism of hypoalbuminemia in rodents

    AU - Koltun, M.

    AU - Nikolovski, J.

    AU - Strong, Kimberley

    AU - Nikolic-Paterson, D.

    AU - Comper, W.D.

    PY - 2005

    Y1 - 2005

    N2 - Normal albumin loss from the plasma is thought to be minimized by a number of mechanisms, including charge repulsion with the capillary wall and an intracellular rescue pathway involving the major histocompatibility complex-related Fc receptor (FcRn)-mediated mechanism. This study investigates how these factors may influence the mechanism of hypoalbuminemia. Hypoalbuminemia in rats was induced by treatment with puromycin aminonucleoside (PA). To test the effects of PA on capillary wall permeability, plasma elimination rates were determined for tritium-labeled tracers of different-sized Ficolls, negatively charged Ficolls, and 14C-labeled tracer of albumin in control and PA-treated Sprague-Dawley rats. Urinary excretion and tissue uptake were also measured. Hypoalbuminemia was also examined in two strains of FcRn-deficient mice: 2-microglobulin ( 2M) knockout (KO) mice and FcRn α-chain KO mice. The excretion rates of albumin and albumin-derived fragments were measured. PA-induced hypoalbuminemia was associated with a 2.5-fold increase in the plasma elimination rate of albumin. This increase could be completely accounted for by the increase in urinary albumin excretion. Changes in the permeability of the capillary wall were not apparent, inasmuch as there was no comparable increase in the plasma elimination rate of 36- to 85-Å Ficoll or negatively charged 50- to 80-Å Ficoll. In contrast, hypoalbuminemic states in 2M and FcRn KO mice were associated with decreases in excretion of albumin and albumin-derived fragments. This demonstrates that the mechanism of hypoalbuminemia consists of at least two distinct forms: one specifically associated with the renal handling of albumin and the other mediated by systemic processes.

    AB - Normal albumin loss from the plasma is thought to be minimized by a number of mechanisms, including charge repulsion with the capillary wall and an intracellular rescue pathway involving the major histocompatibility complex-related Fc receptor (FcRn)-mediated mechanism. This study investigates how these factors may influence the mechanism of hypoalbuminemia. Hypoalbuminemia in rats was induced by treatment with puromycin aminonucleoside (PA). To test the effects of PA on capillary wall permeability, plasma elimination rates were determined for tritium-labeled tracers of different-sized Ficolls, negatively charged Ficolls, and 14C-labeled tracer of albumin in control and PA-treated Sprague-Dawley rats. Urinary excretion and tissue uptake were also measured. Hypoalbuminemia was also examined in two strains of FcRn-deficient mice: 2-microglobulin ( 2M) knockout (KO) mice and FcRn α-chain KO mice. The excretion rates of albumin and albumin-derived fragments were measured. PA-induced hypoalbuminemia was associated with a 2.5-fold increase in the plasma elimination rate of albumin. This increase could be completely accounted for by the increase in urinary albumin excretion. Changes in the permeability of the capillary wall were not apparent, inasmuch as there was no comparable increase in the plasma elimination rate of 36- to 85-Å Ficoll or negatively charged 50- to 80-Å Ficoll. In contrast, hypoalbuminemic states in 2M and FcRn KO mice were associated with decreases in excretion of albumin and albumin-derived fragments. This demonstrates that the mechanism of hypoalbuminemia consists of at least two distinct forms: one specifically associated with the renal handling of albumin and the other mediated by systemic processes.

    U2 - 10.1152/ajpheart.00808.2004

    DO - 10.1152/ajpheart.00808.2004

    M3 - Article

    VL - 288

    SP - H1604-H1610

    JO - American Journal of Phsyiology - Heart and Circulatory Physiology

    JF - American Journal of Phsyiology - Heart and Circulatory Physiology

    SN - 0363-6135

    IS - 4

    ER -