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1 Ludwig Institute for Cancer Research, London, United Kingdom; Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom; Centre for Nephrology and Department of Physiology, Royal Free, University College London, London, United Kingdom
2 Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA
3 Ludwig Institute for Cancer Research, London, United Kingdom; Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom
4 Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, United Kingdom
5 Centre for Nephrology and Department of Physiology, Royal Free, University College London, London, United Kingdom
* To whom correspondence should be addressed. E-mail: robert.unwin{at}ucl.ac.uk.
Polypeptides present in the glomerular filtrate are almost completely reabsorbed in the first segment of the proximal tubule by receptor-mediated endocytosis; in the renal Fanconi syndrome (FS), there is failure to reabsorb many of these polypeptides. We have compared the urinary proteomes of Dent's disease (due to a CLC5 mutation) patients, a form of FS, with normal subjects using 3 different proteomic methods. No differences in the levels of several plasma proteins were detected when standardized to total protein amounts. In contrast, several vitamin and prosthetic group carrier proteins were found in higher amounts in Dent's urine (with respect to total protein). Similarly, complement components, apolipoproteins, and some cytokines represented a larger proportion of the Dent's urinary proteome, suggesting that such proteins are reabsorbed more efficiently than other classes of proteins. Conversely, proteins of renal origin were found in proportionately higher amounts in normal urine. Thus, the uptake of filtered vitamins, which are normally bound to their respective carrier proteins to prevent urinary losses, seems a key function of the proximal tubule; in addition, this nephron segment may also play a critical role in reabsorbing potentially cytotoxic polypeptides of plasma origin, preventing them from acting at more distal nephron sites.
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