Characterization of Renal Papillary Antigen 1 (RPA-1), a Biomarker of Renal Papillary Necrosis

2010 ◽  
Vol 38 (3) ◽  
pp. 346-358 ◽  
Author(s):  
Sally A. Price ◽  
Dai Davies ◽  
Rachel Rowlinson ◽  
Clive G. Copley ◽  
Andrew Roche ◽  
...  

Renal papillary necrosis (RPN) is a relatively common toxicity observed in preclinical drug safety testing. It is also observed in a variety of human diseases. RPN is difficult to diagnose without expensive scanning methods or histopathology. A noninvasive biomarker that could be detected at early stages of kidney damage would be of great value both to preclinical drug safety testing and in the clinic. An antibody raised to an unknown epitope of an antigen in rat kidney papilla was found to be specific for collecting duct cells in the kidney; this was termed renal papillary antigen 1 (RPA-1). In this study, the authors show that RPA-1 is an early biomarker of RPN in two different rat models of toxicity: 2-bromoethanamine (BEA) and N-phenylanthranilic acid (NPAA). RPA-1 can be detected in urine at early stages of toxicity and correlates well with the histopathology observed. We also characterized the biochemical properties of RPA-1 and found that the antigen is a high molecular weight membrane bound glycoprotein, with the epitope likely to be carried on an N-linked carbohydrate structure. This study demonstrates that RPA-1 is an excellent marker of RPN that can be used to detect this toxicity in preclinical safety testing.

1998 ◽  
Vol 26 (1) ◽  
pp. 152-159 ◽  
Author(s):  
Matthias Rinke ◽  
Ernst M. Bomhard ◽  
Heinz Hildebrand ◽  
Karl H. Leser ◽  
Ingo Loof ◽  
...  

2000 ◽  
Vol 113 (7) ◽  
pp. 1277-1285 ◽  
Author(s):  
K.M. McCarthy ◽  
Y. Yoong ◽  
N.E. Simister

The neonatal Fc receptor, FcRn, transports immunoglobulin G (IgG) across cellular barriers between mother and offspring. FcRn also protects circulating IgG from catabolism, probably during transport across the capillary endothelium. Only one cell culture model of transcytosis has been used extensively, the transport of IgA from the basolateral to the apical surface of Madin-Darby canine kidney cells by the polymeric immunoglobulin receptor (pIgR). We report that rat inner medullary collecting duct (IMCD) cells transfected with DNA encoding the (alpha) subunit of rat FcRn specifically and saturably transport Fc when grown as polarized monolayers. Using this system, we have found that transcytosis by FcRn, like transcytosis by the pIgR, depends upon an intact microtubule system. FcRn differs most strikingly from the pIgR in its ability to transport its ligand in both the apical to basolateral and basolateral to apical directions. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibited basolateral to apical transport by FcRn more than apical to basolateral transport, suggesting that there are differences in the mechanisms of transport in the two directions. Lastly, we found that transcytosis by FcRn depends upon vesicular acidification. We anticipate that the IMCD cell culture model will allow further elucidation of the mechanism of IgG transport by FcRn.


1961 ◽  
Vol 41 (4) ◽  
pp. 1033-1041 ◽  
Author(s):  
David C. Utz ◽  
Lewis B. Woolner ◽  
Llewelyn P. Howell

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