Protection from radiation nephropathy by WR-2721.

The efficacy of WR-2721 pretreatment against radiation injury to the growing kidney was evaluated in the weanling mouse. Immediately following unilateral nephrectomy, animals received intraperitoneal injections of saline or WR-2721 (220 mg/kg). Thirty minutes later both nonprotected (saline-treated) control animals and protected (WR-2721-treated) animals received 1000-rad single-fraction radiation to the remaining kidney. Other animals received WR-2721 immediately following unilateral nephrectomy but no radiation. Animals were sacrificed at 3 and 24 weeks. Nonirradiated animals treated with WR-2721 only showed normal compensatory renal growth, body growth, and renal function at 24 weeks. The nonprotected, irradiated animals exhibited renal growth inhibition without body growth inhibition, and renal functional abnormalities including elevation of serum BUN and reduction of glomerular filtration rate. Pretreatment with WR-2721 prior to 1000 rad prevented the renal growth inhibition and functional abnormalities seen in the nonprotected irradiated animals. Within the observation period there were no differences in renal morphology by light and electron microscopy between protected and nonprotected groups; only mild glomerular and tubular abnormalities compatible with radiation injury were seen. WR-2721 can modulate renal radiation injury; however, the growth and functional protection is not well correlated with specific histologic change. The dose reduction factor for WR-2721 renal growth protection is between 1.16 and 1.2. WR-2721 may have future clinical utility by increasing radiation tolerance of the kidney.