Microalbuminuria in Type 1 Diabetes Is Associated With Enhanced Excretion of the Endocytic Multiligand Receptors Megalin and Cubilin

  1. Kathryn M. Thrailkill, MD1,
  2. Teresa Nimmo, MD1,
  3. R. Clay Bunn, PHD1,
  4. Gael E. Cockrell, 1,
  5. Cynthia S. Moreau1,
  6. Samuel Mackintosh, PHD2,
  7. Ricky D. Edmondson, PHD3 and
  8. John L. Fowlkes, MD1
  1. 1Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas;
  2. 2Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
  3. 3Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
  1. Corresponding author: Kathryn M. Thrailkill, thrailkillkathrynm{at}uams.edu.

Abstract

OBJECTIVE Proteinuria is the hallmark of diabetic nephropathy; yet, glomerular histology does not fully explain mechanisms contributing to proteinuria. Our objective was to identify proteins in the urine of individuals with type 1 diabetes and microalbuminuria that might implicate a mechanistic pathway operative in proteinuria.

RESEARCH DESIGN AND METHODS Using a GeLC/MS platform proteomics approach, we compared the urine proteome from 12 healthy nondiabetic individuals, 12 subjects with type 1 diabetes yet normal urinary albumin excretion rates, and 12 subjects with type 1 diabetes and microalbuminuria (type 1 diabetes + microalbuminuria).

RESULTS The abundance of megalin and cubilin, two multiligand receptors expressed in kidney proximal tubule cells and involved with the reuptake of filtered albumin and megalin/cubilin ligands, was significantly increased in type 1 diabetes + microalbuminuria urine, compared with both nonalbuminuric groups.

CONCLUSIONS Aberrant shedding of megalin and cubilin could contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received January 20, 2009.
    • Accepted March 31, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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