CYCLOSPORINE INCREASES RENAL PARATHYROID HORMONE-RELATED PROTEIN EXPRESSION IN-VIVO IN THE RAT

Background. Clinical use of cyclosporine (CsA) is limited by its known nephrotoxicity, Parathyroid hormone (PTH)-related protein (PTHrP) inc reases after acute renal ischemia and stimulates proliferation of rena l cells in culture. Herein, we have examined whether the renal express ion of PTHrP and its PTH/PTHrP receptor is affected by chronic CsA nep hrotoxicity, Methods. Rats were randomly assigned to receive daily int ramuscular injections of either CsA (25 mg/kg) or the same volume of t he vehicle olive oil (control) for 3 weeks, At this time interval, und er ether anesthesia, rat blood and kidneys were obtained for analytica l determinations, and total RNA isolation or immuno-histochemistry, re spectively, Results. Serum urea was 11+/-2 and 6+/-1 mmol/L (P<0.01) i n CsA-treated and control rats, respectively. We found that PTH/PTHrP receptor mRNA was unchanged, but PTHrP mRNA, and also transforming gro wth factor-beta(1) mRNA expression as positive control, was about twof old increased in the kidney of CsA-treated rats, This was accompanied by increased PTHrP immunostaining in renal cortical tubules, associate d with tubule vacuolation. Conclusion. This study demonstrates an up-r egulation of PTHrP, associated with chronic CsA-induced nephrotoxicity , Our findings support a role for PTHrP in the CsA-injured kidney.