A. Garciaocana et al., CYCLOSPORINE INCREASES RENAL PARATHYROID HORMONE-RELATED PROTEIN EXPRESSION IN-VIVO IN THE RAT, Transplantation, 65(6), 1998, pp. 860-863
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.