Renal processing of serum proteins in an albumin-deficient environment: an in vivo study of glomerulonephritis in the Nagase analbuminaemic rat

T.M. Osicka, Kimberley Strong, D.J. Nikolic-Paterson, R.C. Atkins, G. Jerums, W.D. Comper

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Plasma albumin has been considered as important for governing glomerular permselectivity as well as being tubulotoxic in proteinuric states. The purpose of this study was to examine glomerular permselectivity and protein clearance of plasma albumin-deficient Nagase analbuminaemic rats (NAR) in normal and proteinuric states associated with puromycin aminonucleoside nephrosis (PAN) and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) and to compare the results with those of previous studies using Sprague–Dawley rats.Methods. Glomerular permselectivity was measured using tritium-labelled polydisperse Ficoll. In vivo fractional clearance (FC) of albumin, transferrin and immunoglobulin G was measured to include both intact and degraded forms of filtered material. Endogenous protein clearance was analysed using two-dimensional electrophoresis in combination with matrix-assisted laser desorption ionization (MALDI) mass spectrometry.Results. FCs of proteins and Ficoll in control NAR were similar to those found in Sprague–Dawley rats. Despite the lack of serum albumin in NAR, proteinuria and morphological changes observed were also similar to those found in Sprague–Dawley rats, with total protein excretion increasing 6-fold in PAN rats and 4-fold in anti-GBM GN rats with respect to controls. Two-dimensional electrophoresis in combination with MALDI mass spectrometry identified the major proteins being excreted as transferrin and a group of mildly acidic proteins in the MW range 40–50 kDa, namely antithrombin III, kininogen, α-1-antiproteinase, haemopexin and vitamin D-binding protein.Conclusions. Both diseases exhibited similar effects to those observed in Sprague–Dawley rats despite the lack of serum albumin, including inhibition of renal protein degradation. The net changes in protein FC, particularly in the range of radii of 36–55 Å, could not be accounted for by changes in size selectivity as Ficoll FC was little affected by the disease states. This emphasizes the need to reassess the relative importance of changes in renal tubular handling vs changes in glomerular capillary barrier in proteinuric states. These studies also demonstrate that albumin is not a critical factor in governing glomerular permselectivity or proteinuria.
    Original languageEnglish
    Pages (from-to)320-328
    JournalNephrology, Dialysis, Transplantation
    Volume19
    Issue number2
    DOIs
    Publication statusPublished - 2004

    Fingerprint

    Acetylglucosaminidase
    Glomerulonephritis
    Blood Proteins
    Albumins
    Kidney
    Serum Albumin
    Ficoll
    Puromycin Aminonucleoside
    Proteins
    Nephrosis
    Glomerular Basement Membrane
    Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Transferrin
    Proteinuria
    Electrophoresis
    Hemopexin
    Vitamin D-Binding Protein
    Kininogens
    Antithrombin III
    Tritium

    Cite this

    @article{1edcc74f03674ee7a95ec2d0501ea0ce,
    title = "Renal processing of serum proteins in an albumin-deficient environment: an in vivo study of glomerulonephritis in the Nagase analbuminaemic rat",
    abstract = "Plasma albumin has been considered as important for governing glomerular permselectivity as well as being tubulotoxic in proteinuric states. The purpose of this study was to examine glomerular permselectivity and protein clearance of plasma albumin-deficient Nagase analbuminaemic rats (NAR) in normal and proteinuric states associated with puromycin aminonucleoside nephrosis (PAN) and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) and to compare the results with those of previous studies using Sprague–Dawley rats.Methods. Glomerular permselectivity was measured using tritium-labelled polydisperse Ficoll. In vivo fractional clearance (FC) of albumin, transferrin and immunoglobulin G was measured to include both intact and degraded forms of filtered material. Endogenous protein clearance was analysed using two-dimensional electrophoresis in combination with matrix-assisted laser desorption ionization (MALDI) mass spectrometry.Results. FCs of proteins and Ficoll in control NAR were similar to those found in Sprague–Dawley rats. Despite the lack of serum albumin in NAR, proteinuria and morphological changes observed were also similar to those found in Sprague–Dawley rats, with total protein excretion increasing 6-fold in PAN rats and 4-fold in anti-GBM GN rats with respect to controls. Two-dimensional electrophoresis in combination with MALDI mass spectrometry identified the major proteins being excreted as transferrin and a group of mildly acidic proteins in the MW range 40–50 kDa, namely antithrombin III, kininogen, α-1-antiproteinase, haemopexin and vitamin D-binding protein.Conclusions. Both diseases exhibited similar effects to those observed in Sprague–Dawley rats despite the lack of serum albumin, including inhibition of renal protein degradation. The net changes in protein FC, particularly in the range of radii of 36–55 {\AA}, could not be accounted for by changes in size selectivity as Ficoll FC was little affected by the disease states. This emphasizes the need to reassess the relative importance of changes in renal tubular handling vs changes in glomerular capillary barrier in proteinuric states. These studies also demonstrate that albumin is not a critical factor in governing glomerular permselectivity or proteinuria.",
    author = "T.M. Osicka and Kimberley Strong and D.J. Nikolic-Paterson and R.C. Atkins and G. Jerums and W.D. Comper",
    year = "2004",
    doi = "10.1093/ndt/gfg226",
    language = "English",
    volume = "19",
    pages = "320--328",
    journal = "Nephrology, Dialysis, Transplantation",
    issn = "0931-0509",
    publisher = "OXFORD UNIV PRESS UNITED KINGDOM",
    number = "2",

    }

    Renal processing of serum proteins in an albumin-deficient environment: an in vivo study of glomerulonephritis in the Nagase analbuminaemic rat. / Osicka, T.M.; Strong, Kimberley; Nikolic-Paterson, D.J.; Atkins, R.C.; Jerums, G.; Comper, W.D.

    In: Nephrology, Dialysis, Transplantation, Vol. 19, No. 2, 2004, p. 320-328.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Renal processing of serum proteins in an albumin-deficient environment: an in vivo study of glomerulonephritis in the Nagase analbuminaemic rat

    AU - Osicka, T.M.

    AU - Strong, Kimberley

    AU - Nikolic-Paterson, D.J.

    AU - Atkins, R.C.

    AU - Jerums, G.

    AU - Comper, W.D.

    PY - 2004

    Y1 - 2004

    N2 - Plasma albumin has been considered as important for governing glomerular permselectivity as well as being tubulotoxic in proteinuric states. The purpose of this study was to examine glomerular permselectivity and protein clearance of plasma albumin-deficient Nagase analbuminaemic rats (NAR) in normal and proteinuric states associated with puromycin aminonucleoside nephrosis (PAN) and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) and to compare the results with those of previous studies using Sprague–Dawley rats.Methods. Glomerular permselectivity was measured using tritium-labelled polydisperse Ficoll. In vivo fractional clearance (FC) of albumin, transferrin and immunoglobulin G was measured to include both intact and degraded forms of filtered material. Endogenous protein clearance was analysed using two-dimensional electrophoresis in combination with matrix-assisted laser desorption ionization (MALDI) mass spectrometry.Results. FCs of proteins and Ficoll in control NAR were similar to those found in Sprague–Dawley rats. Despite the lack of serum albumin in NAR, proteinuria and morphological changes observed were also similar to those found in Sprague–Dawley rats, with total protein excretion increasing 6-fold in PAN rats and 4-fold in anti-GBM GN rats with respect to controls. Two-dimensional electrophoresis in combination with MALDI mass spectrometry identified the major proteins being excreted as transferrin and a group of mildly acidic proteins in the MW range 40–50 kDa, namely antithrombin III, kininogen, α-1-antiproteinase, haemopexin and vitamin D-binding protein.Conclusions. Both diseases exhibited similar effects to those observed in Sprague–Dawley rats despite the lack of serum albumin, including inhibition of renal protein degradation. The net changes in protein FC, particularly in the range of radii of 36–55 Å, could not be accounted for by changes in size selectivity as Ficoll FC was little affected by the disease states. This emphasizes the need to reassess the relative importance of changes in renal tubular handling vs changes in glomerular capillary barrier in proteinuric states. These studies also demonstrate that albumin is not a critical factor in governing glomerular permselectivity or proteinuria.

    AB - Plasma albumin has been considered as important for governing glomerular permselectivity as well as being tubulotoxic in proteinuric states. The purpose of this study was to examine glomerular permselectivity and protein clearance of plasma albumin-deficient Nagase analbuminaemic rats (NAR) in normal and proteinuric states associated with puromycin aminonucleoside nephrosis (PAN) and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) and to compare the results with those of previous studies using Sprague–Dawley rats.Methods. Glomerular permselectivity was measured using tritium-labelled polydisperse Ficoll. In vivo fractional clearance (FC) of albumin, transferrin and immunoglobulin G was measured to include both intact and degraded forms of filtered material. Endogenous protein clearance was analysed using two-dimensional electrophoresis in combination with matrix-assisted laser desorption ionization (MALDI) mass spectrometry.Results. FCs of proteins and Ficoll in control NAR were similar to those found in Sprague–Dawley rats. Despite the lack of serum albumin in NAR, proteinuria and morphological changes observed were also similar to those found in Sprague–Dawley rats, with total protein excretion increasing 6-fold in PAN rats and 4-fold in anti-GBM GN rats with respect to controls. Two-dimensional electrophoresis in combination with MALDI mass spectrometry identified the major proteins being excreted as transferrin and a group of mildly acidic proteins in the MW range 40–50 kDa, namely antithrombin III, kininogen, α-1-antiproteinase, haemopexin and vitamin D-binding protein.Conclusions. Both diseases exhibited similar effects to those observed in Sprague–Dawley rats despite the lack of serum albumin, including inhibition of renal protein degradation. The net changes in protein FC, particularly in the range of radii of 36–55 Å, could not be accounted for by changes in size selectivity as Ficoll FC was little affected by the disease states. This emphasizes the need to reassess the relative importance of changes in renal tubular handling vs changes in glomerular capillary barrier in proteinuric states. These studies also demonstrate that albumin is not a critical factor in governing glomerular permselectivity or proteinuria.

    U2 - 10.1093/ndt/gfg226

    DO - 10.1093/ndt/gfg226

    M3 - Article

    VL - 19

    SP - 320

    EP - 328

    JO - Nephrology, Dialysis, Transplantation

    JF - Nephrology, Dialysis, Transplantation

    SN - 0931-0509

    IS - 2

    ER -