Evaluation of molecular markers of renal toxicity caused by proximal tubule segment-specific nephrotoxicants in a time-course study

As a consequence of the difficulties in assessing early renal damage by currently available/traditional biomarkers, there is an ongoing interest in developing new biomarkers of nephrotoxicity. An emerging approach to achieve this objective is the use of genomic technologies. The aim of the present study was to monitor by qRT-PCR mRNA levels of some genes specifically expressed in the injured and/or regenerating kidney cells after treatment with segment-specific nephrotoxicants and correlate their changes with histopathological findings and clinical markers (creatinine, urea, glutamine synthetase (GS) of renal damage. Male Wistar rats 8 weeks old were treated (n=4) with single administration of 100 mg/kg b.w. hexachloro-1:3-butadiene (HCBD), or 25 mg/kg b.w. of potassium dichromate (Cr). Kidney and blood samples were collected after 6, 12, 24, 48, 72, and 96 h after treatment. The following genes were evaluated: kidney injury molecule-1 (KIM-1), clusterin (Cln), regucalcin (Rgn), and osteopontin (Spp1) according to their involvement in tissue damage, remodelling and regeneration, disruption of calcium homeostasis, oxidative stress. The selective target site of damage in the renal proximal tubule after treatment with HCBD (pars recta) or Cr (pars convoluta) was confirmed at histopathology. Results showed a good correlation between transcriptomic, biochemical markers and morphological changes in a time-related manner. In conclusion, expression of genes in renal tissue appears an early and sensitive approach to measure kidney injury induced by xenobiotic substances.