In vitro nephrotoxicity testing: Polarized approach of proximal tubular epithelium

1998 ◽  
Vol 95 ◽  
pp. 167
Author(s):  
I. Genestie ◽  
V. Keravec ◽  
J.P. Morin ◽  
J.P. Fillastre
1995 ◽  
Vol 48 (2) ◽  
pp. 536-543 ◽  
Author(s):  
Lorraine C. Racusen ◽  
◽  
Patricia D. Wilson ◽  
Patricia A. Hartz ◽  
Barbara A. Fivush ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Akihiko Saito ◽  
Hiroyoshi Sato ◽  
Noriaki Iino ◽  
Tetsuro Takeda

Receptor-mediated endocytosis is a pivotal function of renal proximal tubule epithelial cells (PTECs) to reabsorb and metabolize substantial amounts of proteins and other substances in glomerular filtrates. The function accounts for the conservation of nutrients, including carrier-bound vitamins and trace elements, filtered by glomeruli. Impairment of the process results in a loss of such substances and development of proteinuria, an important clinical sign of kidney disease and a risk marker for cardiovascular disease. Megalin is a multiligand endocytic receptor expressed at clathrin-coated pits of PTEC, playing a central role in the process. Megalin cooperates with various membrane molecules and interacts with many intracellular adaptor proteins for endocytic trafficking. Megalin is also involved in signaling pathways in the cells. Megalin-mediated endocytic overload leads to damage of PTEC. Further studies are needed to elucidate the mechanism of megalin-mediated endocytosis and develop strategies for preventing the damage of PTEC.


1962 ◽  
Vol 45 (4) ◽  
pp. 643-649 ◽  
Author(s):  
José Carlos Peña ◽  
Richard L. Malvin

The stop flow technique was used to investigate the permeability characteristics of the dog nephron to various C14-labeled non-electrolytes. 12 minutes after clamping the ureter, creatinine, PAH, and C14 compound were injected intravenously. 2 minutes later, urine samples were collected. Urea and glycerol were able to enter the tubular urine along the entire nephron at rates which were commensurate with their molecular weights. No significant movement of larger molecules (D-arabinose, D-glucose, and mannitol) could be detected. However, after administration of twenty units of pitressin, D-arabinose was able to diffuse across the distal and proximal tubular epithelium.


2011 ◽  
Vol 91 (12) ◽  
pp. 1717-1726 ◽  
Author(s):  
Amala Rajasundari ◽  
Laurent Pays ◽  
Patrick Mehlen ◽  
Ganesan Ramesh

2004 ◽  
Vol 164 (6) ◽  
pp. 2175-2187 ◽  
Author(s):  
Stefan Porubsky ◽  
Holger Schmid ◽  
Mahnaz Bonrouhi ◽  
Matthias Kretzler ◽  
Ernst Malle ◽  
...  

1996 ◽  
Vol 10 (3) ◽  
pp. 394-394
Author(s):  
Lorraine C. Racusen ◽  
Patricia D. Wilson ◽  
Patricia A. Hartz ◽  
Barbara A. Fivush ◽  
Christopher R. Burrow ◽  
...  

2008 ◽  
Vol 74 (4) ◽  
pp. 1084-1091 ◽  
Author(s):  
Anja Verhulst ◽  
Rachel Sayer ◽  
Marc E. De Broe ◽  
Patrick C. D'Haese ◽  
Colin D. A. Brown

1989 ◽  
Vol 17 (1_part_1) ◽  
pp. 27-32 ◽  
Author(s):  
Carl L. Alden ◽  
Ronald D. Parker ◽  
David F. Eastman

Chloromethanediphosphonate (Cl2MDP), a cation chelator, is used as a therapeutic for hypercalcemia of malignancy. Cl2MDP exhibits nephrotoxic potential. Thus, a useful model has been developed to study the mechanism of injury. Intraperitoneal administration of highly exaggerated dosages, specifically 200 mg/kg b.i.d., resulted in a consistent mild to moderate extent of kidney damage after the third day of treatment in rats. Proteinuria and lowered serum phosphorus levels occur prior to onset of histopathologic changes. Injury was characterized as necrosis of proximal tubular epithelium with predilection for pars recta. Unlike many renal toxicity models, the necrosis occurs as cell lysis only after 24 to 48 hours of treatment. However, this model significantly reduces the time required to induce renal toxicity observed in routine toxicity studies from months of treatment to less than 1 week and will, thus, serve as a baseline for subsequent pathogenetic studies.


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