Abstract

The objective of the proposed research is to understand the mechanism of the highly specific increase in albumin in kidney basement membranes (glomerular basement membrane, tubular basement membrane) observed by immunofluorescence and quantitative immunoassay in diabetic nephropathy. A similar increase is observed in diabetic muscle capillary and sarcolemmal basement membranes. This study will define whether the increased binding of albumin to basement membranes is a consequence of an alteration in albumin or in renal basement membranes induced by the diabetic state. Diabetic and normal albumin, obtained from sera and kidney eluates, will be evaluated for differences in binding to basement membrane fractions as well as for structural changes. In addition, basement membrane fractions from diabetic kidneys will be studied for changes that lead to increased entrapment of serum proteins. The presence of increased amounts of albumin in basement membranes in kidney may play an important role in the pathogenesis of diabetic renal and vascular disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM026149-07
Application #
3151592
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1979-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Shen, G Q; Butkowski, R; Cheng, T et al. (1990) Comparison of non-collagenous type IV collagen subunits in human glomerular basement membrane, alveolar basement membrane, and placenta. Connect Tissue Res 24:289-301
Kashtan, C E; Michael, A F (1989) Hereditary nephritis. Semin Nephrol 9:135-46
Eddy, A A; Michael, A F (1988) Acute tubulointerstitial nephritis associated with aminonucleoside nephrosis. Kidney Int 33:14-23
Gores, D F; Sutherland, D E; Platt, J L et al. (1987) Lack of tolerance to donor-strain skin grafts in mice with established islet allografts. Transplantation 43:749-50
Kleppel, M M; Kashtan, C E; Butkowski, R J et al. (1987) Alport familial nephritis. Absence of 28 kilodalton non-collagenous monomers of type IV collagen in glomerular basement membrane. J Clin Invest 80:263-6
Falk, R J; Sisson, S P; Dalmasso, A P et al. (1987) Ultrastructural localization of the membrane attack complex of complement in human renal tissues. Am J Kidney Dis 9:121-8
Michael, A F (1986) Immunologic mechanisms in renal disease--an overview. Nippon Jinzo Gakkai Shi 28:873-86
Eddy, A A; Crary, G S; Michael, A F (1986) Identification of lymphohemopoietic cells in the kidneys of normal rats. Am J Pathol 124:335-42
Kleppel, M M; Michael, A F; Fish, A J (1986) Comparison of non-collagenous type IV collagen components in the human glomerulus and EHS tumor. Biochim Biophys Acta 883:178-89
Kleppel, M M; Michael, A F; Fish, A J (1986) Antibody specificity of human glomerular basement membrane type IV collagen NC1 subunits. Species variation in subunit composition. J Biol Chem 261:16547-52

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