Influence of cyclosporine A on adaptive hypertrophy after unilateral nephrectomy in the rat

The functional challenge to a transplanted kidney is comparable to that of a single kidney after unilateral nephrectomy. The single kidney model was used in rats to study the influence of the immunosuppressant CyA. Using this model interference with immunological or preservation/transplantation problems can be excluded. Two month old rats were studied 4 weeks after unilateral nephrectomy. After unilateral nephrectomy the juvenile rats had been fed for 28 days with 10 or 15 mg/kg BW CyA daily. These rats were compared to intact control rats and to age-matched uni-nephrectomized rats. Single kidney weight was measured in one group. Single kidney function was measured in a second group, first in the metabolic cage and then in experiments with isolated kidneys perfused under standard conditions. The glomerular filtration coefficient Kf was measured by micropuncture techniques. Glomerular capillary surface area was estimated after perfusion fixation in order to calculate the effective hydraulic permeability k of the glomerular capillary wall (k = Kf/S). Standard allogeneic skin transplantation across the MHC barrier was used to establish that the CyA dosage used was immunosuppressive. The results showed that the single kidney mass (as a measure of tubular hypertrophy) and GFR were suppressed under the influence of CyA compared to controls. Analysis of glomerular filtration parameters in the isolated perfused kidneys on the single nephron level had the following results: a small increase of the glomerular capillary surface (morphometry) was suppressed under CyA, whereas the effective hydraulic permeability (k) increased by almost 40% whether CyA was given or not.