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Am J Physiol Renal Physiol (August 13, 2008). doi:10.1152/ajprenal.00134.2008
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Submitted on March 13, 2008
Accepted on August 11, 2008

Proteomic analysis of renal calculi indicates an important role for inflammatory processes in calcium stone formation

Michael L. Merchant1*, Timothy Cummins2, Daniel W. Wilkey1, Sarah A. Salyer1, David W. Powell3, Jon B. Klein4, and Eleanor D. Lederer5

1 Medicine, University of Louisville, Louisville, Kentucky, United States
2 Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky, United States
3 Medicine, University of Louisville, Louisville, Kentucky, United States; Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky, United States
4 Medicine, University of Louisville School of Medicine, Louisville, Kentucky, United States; Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky, United States; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States; Veterans Administration Medical Center, Louisville, Kentucky, United States
5 Medicine, University of Louisville, Louisville, Kentucky, United States; Veterans Administration Medical Center, Louisville, Kentucky, United States

* To whom correspondence should be addressed. E-mail: mlmerc02{at}louisville.edu.

Even though renal stones/calculi occur in about 10% of individuals, they are an enormous economic burden to the entire US health system. While the relative metabolic composition of renal calculi are generally known, there is no clear understanding of the genetics of renal stone formation nor are there clear prognostic indicators of renal stone formation. The application of proteomics to the analysis of renal calculi axiomatically holds that insight into renal stone pathobiology can be gained by a more comprehensive understanding of the renal calculi protein composition. We analyzed isolated renal stone matrix proteins using mass spectrometric and immunohistochemical methods identifying 158 proteins with high confidence including 28 common proteins. The abundant proteins included those identified previously in stones and proteins identified here for the first time such as myeloid lineage specific, integral membrane and lipid regulatory proteins. Pathway analyses of all proteins identified suggested that a significant fraction of the most abundant matrix proteins participate in inflammatory processes. These proteomic results support the hypothesis that stone formation induces a cellular inflammatory response and the protein components of this response contribute to the abundant stone matrix proteome.




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