The increase in contralateral kidney mass that follows the removal of one kidney is caused primarily by the
hypertrophy and, to a lesser extent, the
hyperplasia of tubule cells.
Amiloride inhibits the proliferation of cells in tissue culture environments and diminishes compensatory
hyperplasia of liver cells after partial
hepatectomy. In the current study, we determined the extent to which
amiloride diminished the compensatory increase in contralateral kidney weight and
protein content after uninephrectomy. Caworth Farms mice, 3 to 4 months of age, received
amiloride by daily
intraperitoneal injection for 7 days before the left kidney was removed and for an additional 4 days after
nephrectomy. Four days after uninephrectomy, compensatory
hypertrophy was quantified by the increase in weight and
protein content of the right kidney in comparison with the left (R - L divided by L x 100; [weight] +24.7% +/- 2.9% and [
protein] +20.6% +/- 4.4%). Treatment with
amiloride reversibly reduced the compensatory increase in kidney weight and
protein content (dose required to achieve 50% inhibition, 11.4 and 2.4 mg/kg/day, respectively).
Hexamethylene amiloride, an analog with weak affinity for conductive Na+ channels and high affinity for Na+-H+ exchangers, had no effect on compensatory
hypertrophy.
Spironolactone, a natriuretic and antikaliuretic agent of potency similar to that of
amiloride, but with a different cellular mechanism of action, had no effect on compensatory
hypertrophy. We conclude that
amiloride reversibly blunts the compensatory renal
hypertrophy after uninephrectomy in mice by mechanisms that appear to be separate from the
drug's effects to block Na+-H+ exchange and transepithelial Na+ and K+ transport.