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We have reexamined 68 (92%) of 74 donors accepted at this center nine to 15 years ago. There was a moderate but significant increase in BP, and ten donors (15%) were hypertensive at the follow-up. Twenty-six donors (38%) had albumin excretion over 10 micrograms/min or excretion of total protein over 185 mg/24 hr. In four of 16 with increased excretion of total protein, this exceeded 400 mg/24 hr, and in three donors this could be due to an intercurrent disease. Ccr averaged 78.4% of preoperative values, and was less than 50% (range 32 to 49%) in eight donors. The compensatory increase (median 30.5 mliter/min/1.73m2) was inversely correlated with age and BP. Aspects of tubular function were assessed by the diluting capacity during water diuresis and by urinary excretion of beta 2-microglobulin and N-acetyl-beta-glucosaminidase. No consistent abnormalities were observed. A subgroup of donors (N = 32) was compared with a matched control group. Urinary albumin excretion among the donors was significantly higher compared to the controls, both in absolute terms (5.4 vs. 3.3 micrograms/min, P less than 0.002) and as percent of total protein excretion (7.6 vs. 5.7%, P less than 0.05). Otherwise no consistent differences were observed. The development of BP over time warrants further observations, but there is no evidence that uninephrectomy represents a long-term risk to the donors' health.

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The pharmacokinetics of intravenous bolus doses of 1.0 g of mezlocillin were studied in 13 persons with normal and reduced renal functions. In renal failure a moderate increase was observed for the terminal serum half-life (t2fl). This changed from a mean of 1.1 h at a glomerular filtration rate of 100 ml/min to 1.6 h at 10 ml/min. The difference was not statistically significant. The excretion of unchanged drug in urine during 24 h was reduced from a mean of 59.4% (range, 52 to 77) in subjects with glomerular filtration rate above 50 ml/min to 10% (range, 7.9 to 12.1) in two patients with glomerular filtration rate of 10 to 20 ml/ min. The volume of distribution during the ,B-phase, Vd, , was 14% of the body weight. Much of the antibiotic was metabolized, and this proportion increased upon reduction in renal function.Mezlocillin is one of the newer penicillins with broad-spectrum activity comprising multiresistant enterobacteria, anaerobes, and Pseudomonas aeruginosa (6). The pharnacokinetics have been studied in subjects with normal renal function (1,5,7,8).The present communication reports on pharmacokinetic changes with reduction in renal function.MATERIALS AND METHODS Antibiotic. Mezlocillin was received from Bayer Chemie AG, Leverkusen, West Germany. One dose of 1.0 g was given as a 10% aqueous solution by intravenous bolus (2-min) injection.Patients. Studied were 13 informed volunteer patients referred to the Medical Department B for assessment of renal function (Table 1). Other antibacterial drugs were not given concomitantly. The patients were supine during the study.Samples. Blood samples were withdrawn from a cubital vein (not same arm as used for injection) at 0, 0.5, 1, 2, 3. 5,6,8, 12, and 24 h after medication. The zero-time sample was taken immediately after the injection was completed. Urine was collected for the periods 0 to 3, 3 to 4, 4 to 8, 8 to 12, and 12 to 24 h postprandially. A permanent urethral catheter and bladder lavage ensured complete recovery of urine for each time interval. Urine volumes were measured, and 10-ml samples were taken from each portion. Serum was separated within 1.5 h. All samples were stored at -20°C to avoid inactivation before assay.Assay. The concentrations were determined by an agar diffusion technique, with well reservoirs filled with 0.5-ml samples and Escherichia coli as the test strain (3). Square plates (16 by 16 cm) with 16 holes and random distibution (Latin square) of standards and samples in triplicate were used. Incubation temperature was 37°C. The assay could measure down to 0.4 ug/ml. The experimental error was 3 to 7% of the observed levels.Calculations. For pharmacokinetic evaluations, curve fitting was done with the AUTOAN 2/NONLIN program of Wagner, Sedman, and Metzler (9). For patients 5, 7, and 12, the best-curve fit was achieved by the first-order, one-compartment open model, whereas the majority of the curve fitting was best with the first-order, two-compartment open model. The values obtained from the two-compartment program were the rate c...