In this paper we describe an experimental model designed for studies of continuous ambulatory peritoneal dialysis (CAPD) in uremic rabbits. We preferred the study of uremic animals because it is not known whether peritoneal membrane differs between normal and uremic animals. Animals made uremic after bilateral nephrectomy could not survive on dialysis. Instead, partial nephrectomy of one kidney and partial (5/6) destruction of the cortex of the remaining kidney by electrocauterization provided a simple and reproducible model. CAPD resulted in adequate control of uremia but the animals showed significant decreases in total plasma proteins and weight. This model is suitable for studies of the metabolic complications of CAPD.

Dialysate effluent protein content was measured in 22 patients undergoing continuous ambulatory peritoneal dialysis (9 with and 13 without previous peritonitis). The average amount of protein in those patients without peritonitis was 1.3 g/2 liters exchanged over a 6-hour period, while that of patients with previous peritonitis was 2.6 g/ 2 liters exchanged over the same period. 71 % of protein found in the dialysate of 2 patients was albumin. Despite the difference in the amount of protein lost between those without and those with peritonitis, there was no significant difference in their mean serum albumin levels (3.2 and 3.4 g%, respectively) which were only slightly below the normal range. The previously reported high protein losses in patients undergoing CAPD are probably the result of frequent episodes of peritonitis and a higher number (five) of daily exchanges.

To find the ideal dialysate flow rate and exchange volume for use in long-term peritoneal dialysis, 10 patients were studied over a period of 1.5 yr. Exchange volumes of 1 or 2 liters and dialysate flow rates of 1, 2, 3, 4, and 6 liters/hr were tested. Dextrose concentration remained constant at 1.5 g/100 ml. Peritoneal clearances for BUN, creatinine, and uric acid were calculated at 2, 5, 10, 15, and 20 hr during dialysis making a total of 120 clearances for each patient. All patients used a reverse osmosis automatic machine. The clearance of all three solutes tended to be higher with exchange volumes of 2 liters than they did with 1 liter; this trend was significant for BUN (P less than 0.025) and uric acid (P less than 0.025) but not for creatinine. There was a significant rise in clearance with increasing flow rates per hour for all solutes as shown in the following table. (Formula: see text), Since patients could not tolerate a flow rate of 6 liters/hr, we conclude that flow rate of 4 liters/hr with a 2-liter exchange will give maximum efficiency.

The kinetic disposition of a single intravenous dose of ceftriaxone (250 to 665 mg) was studied in six normal subjects and nine patients with renal insufficiency and normal hepatic function. In normal subjects, ceftriaxone was eliminated with a t1/20 of 5.2 h (range, 4.1 to 5.8). The total body clearance (Qb) was 13.5 ml/kg per h (range, 8.4 to 23.3), and renal clearance was 8.3 ml/kg per h (range, 5.8 to 13.3). In patients with severe renal insufficiency requiring peritoneal or hemodialysis, the mean tl2p was prolonged to 13.4 h (range, 7.7 to 15.8) and the mean Qb was reduced to 6.9 ml/kg per h (range, 3.4 to 12.8). The apparent volumes of distribution (V, and V5,) were not different from those determined in normal subjects. Peritoneal dialysis did not remove ceftriaxone. The dialysate of three patients on continuous peritoneal dialysis did not contain any measurable ceftriaxone, and the kinetic disposition in these patients was similar to the hemodialysis patients between their dialysis treatment. During a 4-h hemodialysis session, the total body clearance of ceftriaxone was reduced, perhaps secondary to a decrease in hepatic blood flow induced by the hemodialysis procedure. After a 12-or 24-h dose regimen, predicted trough concentrations of ceftriaxone in plasma at steady state derived from kinetic data generated from the study and assuming linear pharmacokinetic behavior were well above the minimum inhibitory concentrations of most sensitive bacteria, suggesting the feasibility of a once-a-day dosage regimen especially for patients with severe renal insufficiency.