Minimal change-like glomerular alterations induced by a human plasma factor

P. K. Cheung*, P. A. Klok, W. W. Bakker

*Corresponding author for this work

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    Abstract

    Circulating factors, including the plasma protease (100KF) described previously, have been suspected to play a role in the pathogenesis of minimal change disease (MCD) for several decades. This factor was able to induce MCD-like alterations in kidney tissue in vitro, i.e. impairment of glomerular polyanion (GPA), as well as glomerular ecto-ATPase. We conducted permeability studies using alternate perfusion of the rat kidney ex vivo according to standard techniques. Either native 100KF (n = 7) or control factor (n = 7) perfusion, followed by perfusion with diluted rat serum was carried out, while urine samples were collected by ureter cannulation. Total urinary protein (by spectrophotometry) as well as IgG (by ELISA) and albumin (by rocket electrophoresis) were measured. Sections of perfused kidneys were stained (immuno-) histochemically for GPA and glomerular ecto-ATPase, and the stainability was quantified using image analysis and expressed as arbitrary units. The results show significantly increased protein leakage after perfusion of 100KF versus control factor(150.0 +/- 48.9 vs. 33.2 +/- 7.7 mu g/min, p less than or equal to 0.01), while the IgG/albumin ratio has decreased(12.0 +/- 9.4 vs. 26.9 +/- 14.4%, p less than or equal to 0.01). Plasma protein leakage after 100KF perfusion is associated with a significant loss of GPA (57.3 +/- 27.5 vs. 98.4 +/- 12.0, p less than or equal to 0.01) and significant decrease of glomerular ecto-ATPase expression (28.7 +/- 11.5 vs. 79.5 +/- 15.0, p less than or equal to 0.001). The capability of 100KF to induce MCD-like glomerular lesions, in association with selectively increased permeability for plasma proteins, suggests that this human plasma constituent may be important in the pathogenesis of MCD.

    Original languageEnglish
    Pages (from-to)586-593
    Number of pages8
    JournalNephron
    Volume74
    Issue number3
    DOIs
    Publication statusPublished - Nov-1996

    Keywords

    • minimal change nephrotic syndrome
    • permeability factor
    • selective permeability
    • glomerular ecto-ATPase
    • CHANGE NEPHROTIC SYNDROME
    • RAT-KIDNEY
    • ADENOSINE DIPHOSPHATASE
    • ANTITHROMBOTIC ACTIVITY
    • FILTRATION BARRIER
    • CHANGE NEPHROPATHY
    • BASEMENT-MEMBRANE
    • POLYANION GPA
    • ANIONIC SITES
    • LYMPHOCYTE-T

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