Preservation of renal compensatory growth in uninephrectomized rats by low-dose cyclosporine

The growth-inhibitory effect of prednisone is a serious drawback to its use in kidney graft recipients. At high doses, cyclosporine also inhibits somatic growth in animals. Furthermore, cyclosporine, in addition to being nephrotoxic in patients, is reported to inhibit compensatory renal growth in uninephrectomized rats. It is unclear whether the latter effect is specific to the kidney. In the present study, we have tested, in the uninephrectomized rat model, the effect of a low dose cyclosporine that is immunosuppressive but does not inhibit somatic growth. Compared with sham operation, uninephrectomy resulted in a significantly greater kidney-to-body weight ratio 2 and 7 days postsurgery. In uninephrectomized rats treated daily with 10 mg/kg cyclosporine s.c., compensatory renal growth was intact. Kidney wet weight, dry weight, and kidney-to-body weight ratios were similar in vehicle and cyclosporine treated, uninephrectomized animals. Similarly, body weight, food consumption, and size of other organs were not adversely affected by the 10 mg/kg/day cyclosporine treatment. Thus, by reducing cyclosporine to levels that are not generally toxic, renal growth is preserved. Our results suggest that the present trend toward using lower doses of cyclosporine in kidney transplant recipients will not only reduce nephrotoxicity, but will also be of benefit in terms of somatic and renal growth, which are important considerations in pediatric transplant patients.