Potential use of isolated glomeruli and cultured mesangial cells as in vitro models to assess nephrotoxicity

The purpose of this short review is to present the potential of using isola ted glomeruli and cultured mesangial cells as two different in vitro models to assess the glomerular effect of molecules with nephrotoxic properties. The advantage of using isolated renal glomeruli is that they conserve the a rchitecture of this anatomical region of the kidney; moreover, they are fre e of any vascular, nervous or humoral influences derived from other regions of the kidney. Mesangial cells are perivascular pericytes located within t he central portion of the glomerular tuft between capillary loops. Mesangia l cells have a variety of functions including synthesis and assembly of the mesangial matrix, endocytosis and processing of plasma macromolecules, and control of glomerular hemodynamics, mainly the ultrafiltration coefficient K-f, via mesangial cell contraction or release of vasoactive hormones. Mos t authors agree that mesangial cells play a major role in glomerular contra ction, filtration surface area, and K-f regulation. One of the major effect s of toxicants on glomerular structures is contraction. We can assess quant itatively the degree of toxicant-induced mesangial cell contraction or glom erular contraction by measuring the changes in planar cell surface area or apparent glomerular cross-sectional area after exposition to the toxicant. These in vitro models can also reveal glomerular effects of xenobiotics tha t are difficult or impossible to observe in vivo. In addition, these studie s permit a fundamental examination of the mechanism of action of xenobiotic s on glomerular cells, including the possibility that at least a part of th eir effects are mediated by local mediators released by glomerular cells. W e review the effects and the mechanisms of action of several toxicants such as gentamicin, cyclosporin, cisplatin, and cadmium on isolated glomeruli o r cultured mesangial cells. As such in vitro results confirm in vivo renal hemodynamic changes caused by toxicants, we conclude that these models are fruitful tools for the study of renal toxicity. These in vitro systems migh t also serve as a predictive tool in the evaluation of drugs inducing chang es in glomerular filtration rate and as a way to propose protective agents against these dramatic hemodynamic effects.