Abstract

The objective of the proposed research is to gain new insights into the pathogenesis of renal disease mediated by immunologic mechanisms through a comprehensive study of the factors influencing and the consequences of tubular immune complex formation and clearance through an analysis of the kinetics of tubular deposition of antibodies to Tamm-Horsfall protein(TH). Specific objectives include evaluation of the effects of altered glomerular permeability and of urinary obstruction on the renal localization of anti-TH antibodies. These studies will include the use of immunologic, biochemical, ablative and naturally occurring models of glomerular injury in rats and cogenital hydronephrosis and ureteral ligation. They will include use of active immunization with TH and quantitative pair-label radioisotope techniques using affinity purified antibodies. Other proteins which interact with and are normally present in the same nephron segment as TH will also be studied. The methods employed will include quantitative biochemical, radioisotope, immunologic and immunopathologic techniques. These studies will be performed in rats, mice, and rabbits.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK033501-05
Application #
3231909
Study Section
Pathology A Study Section (PTHA)
Project Start
1983-08-01
Project End
1990-11-30
Budget Start
1987-12-15
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Weaver, Matthew L; Qiu, S Roger; Hoyer, John R et al. (2009) Surface aggregation of urinary proteins and aspartic Acid-rich peptides on the faces of calcium oxalate monohydrate investigated by in situ force microscopy. Calcif Tissue Int 84:462-73
Wang, Lijun; Qiu, S Roger; Zachowicz, William et al. (2006) Modulation of calcium oxalate crystallization by linear aspartic acid-rich peptides. Langmuir 22:7279-85
Tang, R; Nancollas, G H; Giocondi, J L et al. (2006) Dual roles of brushite crystals in calcium oxalate crystallization provide physicochemical mechanisms underlying renal stone formation. Kidney Int 70:71-8
De Yoreo, James J; Qiu, S Roger; Hoyer, John R (2006) Molecular modulation of calcium oxalate crystallization. Am J Physiol Renal Physiol 291:F1123-31
Weaver, Matthew L; Qiu, S Roger; Hoyer, John R et al. (2006) Improved model for inhibition of pathological mineralization based on citrate-calcium oxalate monohydrate interaction. Chemphyschem 7:2081-4
Elhadj, S; De Yoreo, J J; Hoyer, J R et al. (2006) Role of molecular charge and hydrophilicity in regulating the kinetics of crystal growth. Proc Natl Acad Sci U S A 103:19237-42
Qiu, S Roger; Wierzbicki, Andrzej; Salter, E Alan et al. (2005) Modulation of calcium oxalate monohydrate crystallization by citrate through selective binding to atomic steps. J Am Chem Soc 127:9036-44
Qiu, S R; Wierzbicki, A; Orme, C A et al. (2004) Molecular modulation of calcium oxalate crystallization by osteopontin and citrate. Proc Natl Acad Sci U S A 101:1811-5
Bleyer, Anthony J; Hart, Thomas C; Shihabi, Zak et al. (2004) Mutations in the uromodulin gene decrease urinary excretion of Tamm-Horsfall protein. Kidney Int 66:974-7
Hoyer, J R; Asplin, J R; Otvos, L (2001) Phosphorylated osteopontin peptides suppress crystallization by inhibiting the growth of calcium oxalate crystals. Kidney Int 60:77-82

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