Renal cell adaptation to oxalate

Abstract

Renal manifestations of chronic hyperoxaluria include nephrolithiasis and, when extreme, interstitial scarring and progressive loss of function. Exposure of cultured renal cells to oxalate has been reported to cause cell death, as well as proliferation. The current study was performed to assess the time course and cell-type specificity of these responses. Proximal (LLC-PK(1)) and distal [cIMCD and primary human renal (HRC1)] renal epithelial cells, as well as interstitial KNRK cells, were exposed to oxalate (0.5-2.0 mM) for 24-72 h. The generation of reactive oxygen species (ROS) was measured using the fluorescent probe DCF, and cell number was determined with CyQuant reagent. HSP-70 expression was assessed via real time PCR and quantitative Western blot. In response to all oxalate concentrations (0.5-2.0 mM) and lengths of exposure (15 min-2 h), cultured proximal and distal renal epithelial cells and renal fibroblasts generated ROS. After 24 h, cells demonstrated initial cell death and decrease in cell numbers, but by 48-72 h adapted and grew, despite the continued presence of oxalate. This response was associated with increased expression of HSP-70 mRNA and protein. Renal cells in vivo may possess adaptive mechanisms to withstand chronic hyperoxaluria, including increased expression of chaperone molecules such as HSP-70.