Serum Advanced Glycosylation End-Products in Patients on Hemodialysis and CAPD

ObjectivesPart I: To evaluate the long-term effects of daily glucose absorption from the peritoneal dialysis fluid on the formation of low-molecular-weight advanced glycosylation end products (AGE-peptides) in nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients. Part II: To determine the acute effect of CAPD on serum AGE-peptide concentrations.DesignPart I: Noninterventional, parallel, cross-sectional clinical trial. Part II: Crossover clinical trial.SettingA university-based hospital, and clinics.PatientsPart I: Sixty nondiabetic subjects recruited into three age-matched (:1:5 years) groups, as follows: 20 healthy volunteers (controls); 20 hemodialysis patients; and 20 CAPD patients. Part II: Eight patients with diabetes mellitus (type lor II) and chronic renal failure who were about to undergo CAPD.InterventionPart I: None. Part II: Uninterrupted CAPD, as medically required.MeasurementsPart I: To determine serum AGEpeptide concentrations blood samples were obtained randomly from controls and CAPD patients, and predialysis from hemodialysis patients. Hemoglobin A1c was also measured in all subjects. Part II: To determine serum AGE-peptide concentrations, blood samples were collected within one month prior to initiation of CAPD (predialysis) and, again, one week after initiation of uninterrupted CAPD (postdialysis). Hemoglobin A1c was measured predialysis.ResultsPart I: Mean hemoglobin A1c values for all groups were within the normal range; however, the mean value for CAPD patients was significantly higher than for both hemodialysis patients and healthy controls (controls, 5.21%:1:0.6%; hemodialysis, 5.12%:1:0.5%; CAPD, 5.78%:1:0.6%; p &lt; 0.01). The dialysis patients had a significantly higher mean serum AGE-peptide concentration than the control subjects (controls, 7.02:1:3.4 units/mL; hemodialysis, 11.9:1:3.6 units/mL; CAPD, 11.1:1:4.5 units/mL; p &lt; 0.01). There was no difference in the mean serum AGE-peptide concentration of patients in the hemodialysis and CAPD groups. Part II: The mean hemoglobin A1c value in the diabetic predialysis patients was 9.2%:1:1.9%. There was no difference between the predialysis and postdialysis serum AGE-peptide concentrations (predialysis, 16.9:1:9.6 units/mL; postdialysis, 16.0:1:2.9 units/mL; p = 0.78).ConclusionsDespite the increased glucose load and the higher hemoglobin A1c values, indicating poor glycemic control, nondiabetic CAPD patients did not have higher serum AGEpeptide concentrations than the nondiabetic hemodialysis patients. In diabetic patients, CAPD did not further increase the serum concentrations of AGEpeptides.</jats:sec

Pharmacokinetics and ex vivo susceptibility of cefpodoxime proxetil in patients receiving continuous ambulatory peritoneal dialysis.

Pharmacokinetics of cefpodoxime, an extended-spectrum cephalosporin, were determined for eight noninfected patients on continuous ambulatory peritoneal dialysis (CAPD) and eight healthy volunteers. Subjects were matched for sex, age (+/- 6 years), and body weight (+/- 10 kg, except for one pair) and received a single 200-mg (cefpodoxime equivalents) oral dose of the prodrug cefpodoxime proxetil in an open-label, paired-design fashion. Dialysate (CAPD group only), plasma, and urine samples were collected and assayed for cefpodoxime by a microbiologic method. In addition, mean bactericidal titers of the effluent dialysate against selected bacterial strains often associated with CAPD-related peritonitis were determined at 6 and 24 h after the dose. There was a significant difference (P < 0.05) in all pharmacokinetic parameters between healthy and CAPD subjects, except for lag time to absorption. The mean peak plasma cefpodoxime concentration of 1.88 +/- 0.6 micrograms/ml occurred at 2.44 +/- 0.5 h for healthy volunteers, while the peak concentration of 3.25 +/- 1.4 micrograms/ml occurred at 12.0 +/- 4.2 h for patients on CAPD. The average elimination half-life in CAPD patients was approximately 12 times greater than that seen in healthy volunteers. Peritoneal dialysis had a minimal effect on cefpodoxime clearance. In healthy volunteers, 24.2% +/- 13% of the dose was recovered from the urine, in contrast to only 5.59% +/- 6.9% for CAPD patients. The mean bactericidal titers for all CAPD patients, at 6 and 24 h, were mostly less than 1:2 and did not exceed 1:4 for any of the isolates. Because of the decreased renal clearance and negligible dialysate clearance of cefpodoxime, and delayed drug absorption, the dosage interval for cefpodoxime proxetil may need to be extended in CAPD patients