Effect of protein intake on renal function and structure in partially nephrectomized rats.

To examine the effect of high protein intake on renal function and structure in rats with 5/6 nephrectomy chronic renal failure, we pairfed rats with chronic renal failure and sham-operated control rats diets of 14 or 37% protein content for up to 6 months. High protein intake accelerated mortality in rats with chronic renal failure and resulted in a more rapid rate of decrease in renal function as established by plotting the reciprocal of plasma creatinine versus time. High protein intake also increased urine protein excretion in experimental and control rats. High protein intake was associated with increased tubular dilatation and interstitial inflammation, both of which were striking features in rats with chronic renal failure. Glomerular sclerosis was prominent in rats with chronic renal failure. These rats had smaller glomerular tuft dimensions than control rats irrespective of their protein intake. We conclude that high protein intake accelerates the course of chronic renal failure in rats. The pathologic process involves glomerular sclerosis; however, interstitial inflammation and renal tubular changes leading to cyst formation also appear to influence the process adversely.

Multiple-dose ciprofloxacin kinetics in normal subjects.

To determine multiple-dose kinetics of the quinoline carboxylic acid derivative ciprofloxacin, we gave 12 normal subjects ciprofloxacin, 250 mg by mouth every 12 hr for 13 doses. Plasma concentrations were measured by HPLC after the first, seventh, and thirteenth doses. Peak and trough plasma concentrations were measured daily. Ciprofloxacin was rapidly absorbed from the gastrointestinal tract and reached maximum serum concentrations about 1 hr after dosing. Ciprofloxacin elimination t1/2 increased from 3.71 hr after the first dose to 6.51 hr after the thirteenth dose (P less than 0.05). Apparent plasma clearance decreased from 0.823 to 0.629 l/kg/hr because of decreased nonrenal clearance. Drug cumulation did not occur throughout the experiment. We conclude that concentrations of ciprofloxacin in excess of the minimum inhibitory concentrations for many important pathogens can be achieved in plasma and that controlled clinical trials of ciprofloxacin efficacy in selected systemic infections are warranted.