Unbound MEDLINE

Elevated urinary excretion of immunoglobulins in nonproteinuric patients with type 1 diabetes.

Abstract

Increased albuminuria is a hallmark of early diabetic nephropathy, whereas the role of immunoglobulins (Igs), such as IgG (its 1-4 subtypes), IgA, and IgM, different in charge and size, has not been examined in early nephropathy in the past due to lack of a sensitive and reliable method. Our study group consisted of subjects with type 1 diabetes (T1D) and normoalbuminuria (n = 78), microalbuminuria (n = 78), and of 75 healthy subjects (HS). A Luminex-based immunoassay (1,000 time more sensitive than nephelometry-based method) was validated for the urine matrix and used for the measurements of IgG1-4, IgA, and IgM in our study groups. The Luminex-based assay detected Igs in 87% of HS subjects and in 100% of T1D subjects. Recovery of known amounts of Igs added to urine was 92-118%. In the normoalbuminuria group, urinary concentrations of albumin, IgG2, IgA, and IgM were significantly higher than in HS, whereas in the microalbuminuria, further elevation of IgG2, IgG4, and IgA was the most pronounced. In all three groups, fractional excretion of Igs was at least 100 times lower than that of albumin. Fractional excretion of IgG2 was the highest among all Igs. We validated a sensitive method for measuring Igs in urine using Luminex. We found that elevated concentrations of Igs, particularly in IgG2 and IgA, is present in subjects with T1D and no proteinuria. Elevation of those particular Ig subtypes suggests a contribution of novel mechanisms in early diabetic nephropathy, different from charge and size barrier impairment.

Links

  • PMC Free PDF
  • Publisher Full Text
  • Authors

    Gohda T, Walker WH, Wolkow P, Lee JE, Warram JH, Krolewski AS, Niewczas MA

    Institution

    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.

    Source

    American journal of physiology. Renal physiology 303:1 2012 Jul pg F157-62

    MeSH

    Adult
    Diabetes Mellitus, Type 1
    Diabetic Nephropathies
    Female
    Humans
    Immunoglobulins
    Male
    Proteinuria

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22513848