Toxicity of Cisplatin and Mercuric Chloride in Human Kidney Cortical Slices

Abstract

1 Organ specific toxicity such as nephrotoxicity is often investigated with the use of in vivo or in vitro animal models.

2 It would be beneficial if these findings could be verified in a human in vitro system which utilizes non-transplantable human kidneys.

3 Non-transplantable human kidneys were decapsulated, cut in half along the long axis, cores made perpendicular to the hemisphere, and precision-cut renal cortical slices produced.

4 These human kidney slices were incubated for 3, 6, 12, 18 and 24 h, viability assessed using intracellular K+ content, protein synthesis and organic ion transport and the potential nephrotoxicity of cisplatin (0.25, 0.5 and 1.0 mM) and mercuric chloride (10, 50 and 100 μm) on these slices were examined.

5 Control human kidney slices were viable for up to 24 h using all viability parameters while a dose-and time-dependent toxic response was seen using both cisplatin and mercuric chloride.

6 Cisplatin was more nephrotoxic in this human in vitro system than in previously investigated in vitro animal systems whereas mercuric chloride was similar in both systems.

7 These results indicate that human renal cortical slices are useful in predicting and verifying potentially nephrotoxic compounds in man.