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TRANSLATIONAL PHYSIOLOGY

The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells

¹Ludwig Institute for Cancer Research, London W1W 7BS; ²Department of Biochemistry and Molecular Biology and ³Centre for Nephrology and Department of Physiology, Royal Free and University College Medical School, University College London, London NW3 2PF; ⁵Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge CB2 ZQR, United Kingdom; and ⁴Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-0626

Submitted 20 January 2004 ; accepted in final form 3 May 2004

Polypeptides present in the glomerular filtrate are almost completely reabsorbed in the first segment of the proximal tubule by receptor-mediated endocytosis; in renal Fanconi syndrome (FS), there is failure to reabsorb many of these polypeptides. We have compared the urinary proteomes in patients with Dent’s disease (due to a CLC5 mutation), a form of FS, with normal subjects using three 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.

kidney; urine; proteomics; mass spectroscopy

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