Enhanced end-organ responsiveness of the uremic kidney to the natriuretic factor.

In chronic renal disease, the addition of a fixed quantity of Na to the extracellular fluid (ECF) will evoke a natriuretic response per nephron which is inversely proportional to the glomerular filtration rate (GFR). One factor that could contribute to this "magnification" phenomenon is an increased sensitivity of residual nephrons to physiologic natriuretic forces. The present studies were designed to examine this possibility. Natriuretic urine fractions from uremic patients, infused into one renal artery of normal rats, produced a small but significant unilateral natriuresis. Infusion of the same fractions in identical amount into remnant kidneys of stage II nonuremic rats (i.e., rats with a contralateral normal kidney in situ) produced a natriuresis in the remnant kidney only which was equivalent to that observed in the normal kidneys. The i.v. infusion of natriuretic fractions into stage II rats produced comparable increments in the fractional excretion of sodium (FENa) bilaterally. However, when the natriuretic fractions were infused into remnant kidneys of stage III rats (no contralateral kidney), deltaFENa was significantly greater than in the foregoing groups. Because stage III rats have increased control values for FENa, baseline FENa was increased to an equivalent level in normal rats by unilateral renal denervation. Natriuretic factor was administered into the ipsilateral renal artery. Although the natriuretic response was increased, it was significantly less than in the stage III remnant kidneys. The data support the view that the uremic state per se is associated with an enhanced responsiveness of the residual nephrons to the natriuretic factor found in the urine (and blood) of uremic patients.