Continuous Ambulatory Peritoneal Dialysis Clearance Research Articles

Pharmacokinetics of Colistin Methanesulfonate and Formed Colistin in End-Stage Renal Disease Patients Receiving Continuous Ambulatory Peritoneal Dialysis

Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recommendations are available for patients receiving CAPD. Eight CAPD patients received a single intravenous CMS dose (150 mg colistin base activity [CBA]) over 30 min. Serial blood and dialysate samples, and cumulative urine where applicable, were collected over 25 h. CMS and colistin concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations were conducted. The total body clearance of CMS (excluding CAPD clearance) was 1.77 liters/h (44%) [population mean (between-subject variability)], while CAPD clearance was 0.088 liter/h (64%). The population mean terminal half-life of CMS was 8.4 h. For colistin, the total clearance/fraction of CMS metabolized to colistin (fm) (excluding CAPD clearance) was 2.74 liters/h (50%), the CAPD clearance was 0.101 liter/h (34%), and the mean terminal half-life was 13.2 h. Monte Carlo simulations suggested a loading dose of 300 mg CBA on day 1 and a maintenance dose of either 150 mg or 200 mg CBA daily to achieve a target average steady-state plasma colistin concentration of 2.5 mg/liter. Clearance by CAPD was low for both CMS and formed colistin. Therefore, CMS doses should not be increased during CAPD. Modeling and simulation enabled us to propose the first evidence-based CMS dosage regimen for CAPD patients.

Dynamic cardiac dyssynchrony is strongly associated with 2-year dialysis adequacy in continuous ambulatory peritoneal dialysis patients

BackgroundLeft ventricular (LV) dyssynchrony is associated with increased risk of all-cause mortality in patients with end-stage renal disease. Our aim was to determine the associations of LV dynamic dyssynchrony with peritoneal solute clearance in continuous ambulatory peritoneal dialysis (CAPD) patients. Our primary objective was to determine the association between dynamic LV dyssynchrony and CAPD clearance at 2 years. Secondary objectives were to identify the factors influencing dynamic dyssynchrony, and to examine the association between dialysis adequacy and echocardiography-assessed LV outcomes.MethodsFifty CAPD patients and 13 healthy volunteers underwent three-dimensional (3D) dobutamine stress echocardiography (DSE). The main endpoint was systolic dyssynchrony index (SDI). Secondary endpoints, including NT-proBNP, troponin I, Kt/V, and biochemical parameters, were measured before stress echocardiography, and Kt/V was measured again 2 years later. All values are expressed as medians and interquartile ranges (IQR).ResultsNT-proBNP (3872 [808–11779] vs. 4.99 [4.99–36.83] pg/mL, P < 0.001), and log NT-proBNP (3.587 [2.896–4.071] vs. 0.698 [0.698–1.540], P < 0.001) levels were significantly higher in the CAPD group than in the control group. Real-time 3D DSE showed that the systolic dyssynchrony index was significantly different between the two groups at the peak dobutamine stage (1.11% [0.76–1.64%] vs. 0.66% [0.50–1.02%], P = 0.004), but not at resting (1.30% [0.89–1.74%] vs. 1.22 % [0.72–1.68%], P = 0.358).The subgroup of patients in the CAPD group with greater improvements in dialysis adequacy had lower baseline dynamic SDI and more favorable echocardiographic findings at 2 years. Dialysis adequacy decreased significantly at 2 year in patients with higher, but not in those with lower dynamic SDI at baseline. In multivariate linear regression analysis, log NT-proBNP and SDI at the peak dobutamine dose were significantly associated with Kt/V and weekly creatinine clearance at 2 years, while log NT-proBNP was significant associated with SDI at the peak dobutamine stage. Female CAPD patients group had more pronounced dynamic LV dyssynchrony compared with male patients.ConclusionsDynamic systolic dyssynchrony was strongly associated with future dialysis adequacy in CAPD patients. Log NT-proBNP was the important predictor of dynamic dyssynchrony. Our study confirmed the concept that cardiac dysfunction has an impact on dialysis adequacy.

Continuous ambulatory peritoneal dialysis: pharmacokinetics and clinical outcome of paclitaxel and carboplatin treatment

PurposeAdministration of chemotherapy in patients with renal failure, treated with hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) is still a challenge and literature data is scarce. Here we present a case study of a patient on CAPD, treated with weekly and three-weekly paclitaxel/carboplatin for recurrent ovarian cancer.ExperimentalDuring the first, second and ninth cycle of treatment, blood, urine and CAPD samples were collected for pharmacokinetic analysis of paclitaxel and total and unbound carboplatin-derived platinum.ResultsTreatment was well tolerated by the patient. No excessive toxicity was observed and at the end of treatment she was in a complete remission. The plasma pharmacokinetics of paclitaxel were unaltered compared to historical data, with neglectable urinary and CAPD clearance. In contrast, the pharmacokinetics of carboplatin were altered, with doubled half-lives compared to patients with normal renal function. Of the administered carboplatin dose, up to 20% was cleared via the dialysate, while only up to 8% was cleared via the urine.ConclusionPaclitaxel and carboplatin can be safely administered to patients with chronic renal failure on CAPD. For paclitaxel the generally applied dose can be administered, and although for carboplatin dose-adjustment is required due to the diminished renal function, the dose can be calculated using Calvert’s formula.

Urea kinetic analysis of automated peritoneal dialysis allows calculation of a CAPD-equivalent Kt/Vurea

Based on evidence of increased mortality with decreasing urea clearance, the Dialysis Outcomes Quality Initiative (DOQI) recommended a weekly Kt/Vurea of 2.0 or higher for patients receiving continuous ambulatory peritoneal dialysis (CAPD). DOQI recommendations for automated peritoneal dialysis (APD) are based on efforts to determine the clearance providing urea mass removal equivalent to CAPD. We have adapted a variable volume direct quantitation urea kinetic model (UKM) in an effort to assess DOQI APD guidelines. The daily urea mass removed with a weekly Kt/Vurea of 2.0 was calculated using standardized CAPD patient profiles. Using this value and defining the pre-APD plasma urea nitrogen (PUN) as C0 and equal to the CAPD steady-state PUN, the UKM reiteratively calculated the urea clearance from an APD treatment that provided a urea mass removal equivalent to CAPD. A total weekly Kt/Vurea was calculated for various levels of continuous urea clearance (defined as Kprt/Vurea) and plotted against Kprt/Vurea (weekly). The impact of dialytic time (t), drain volume of the daytime dwell (delta), and ultrafiltration volume (phi) were assessed, and all profiles were performed with C0 equal to the corresponding blood urea nitrogen of 60, 70, and 80 mg/dL. The relationship between requisite weekly Kt/Vurea and Kprt/Vurea (weekly) was linear. Weekly Kt/Vurea declined with increasing Kprt/Vurea, t, delta, and phi. The effect of phi on the weekly Kt/Vurea was independent of Kprt/Vurea, and the magnitude of the effect of t and delta on the weekly Kt/Vurea decreased with increasing continuous clearance. Weekly Kt/Vurea values were independent of V and C0. The latter observation allowed extrapolation of CAPD clearance and urea generation relationships to APD: CAPD-equivalent weekly Kt/Vurea = [700 x (UD + Ur)]/(C0 x V), where UD and Ur are the daily urea mass (mg) in dialysate and urine, respectively. The APD urea clearance, which provides urea mass removal equivalent to CAPD, varies as a function of a combination of patient and treatment variables. However, a CAPD-equivalent weekly Kt/Vurea can be calculated by collecting appropriate dialysis and urine samples and estimating patient V. The results can be evaluated in the context of evidence-based CAPD guidelines, increasing the precision of adjustment and monitoring of the APD prescription.

Cefotaxime and metabolite disposition in two pediatric continuous ambulatory peritoneal dialysis patients.

To characterize the pharmacokinetics of cefotaxime and desacetylcefotaxime in pediatric patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after intraperitoneal administration of cefotaxime. Case series. Ambulatory children from Children's Hospital nephrology clinic, Columbus, Ohio. Two adolescents without peritonitis. A single intraperitoneal dose of cefotaxime 500 mg per 1 L dianeal was given during CAPD. Cefotaxime and desacetyl-cefotaxime were measured in plasma, urine, and dialysate by HPLC. Maximum plasma concentration (Cmax) of cefotaxime was 11.94 and 13.08 mg/L and that of desacetylcefotaxime 5.73 and 5.33 mg/L. Time to reach maximum concentration (Tmax) of cefotaxime was 2.22 and 4.08 h, and that of desacetylcefotaxime was 5.33 and 5.73 h after instillation of the intraperitoneal cefotaxime dose. Systemic absorption of cefotaxime was 56.6 and 64.8 percent. Total clearance of cefotaxime was 62 and 79 mL/min/1.73 m2. Nonrenal clearance accounted for nearly 95 percent; renal and CAPD clearance contributed approximately 5 percent of the total clearance. Renal and CAPD clearance measurements of desacetylcefotaxime were similar to those for cefotaxime. Cefotaxime half-life was 1.83 and 2.49 h and desacetylcefotaxime half-life was 8.14 and 11.0 h. Cefotaxime was well absorbed and therapeutic serum concentrations were achieved after intraperitoneal administration. Renal and CAPD clearances for cefotaxime and desacetylcefotaxime were low. Cefotaxime nonrenal clearance was unaffected. Further studies are needed to establish appropriate intraperitoneal dosing guidelines of cefotaxime in pediatric CAPD patients.

Problems in Comparisons of Clearances Prescriptions in Hemodialysis and Continuous Ambulatory Peritoneal Dialysis

There is currently great interest in defining acceptable doses of dialysis therapy with different techniques. In hemodialysis (HD) and in continuous ambulatory peritoneal dialysis (CAPD), doses of weekly clearances of urea and/or creatinine required for achieving acceptable nutrition and quality of life need better definition (1–2). If control of the peak blood urea nitrogen concentration (BUN) is important in preventing uremic toxicity (the peak concentration hypothesis), then any intermittent therapy requires a greater dose of therapy to maintain the peak concentration below or at the steady state value of CAPD (assuming the same urea nitrogen generation rate and, hence, the same weekly net removal [mass transfer] of urea nitrogen) (2). The peak concentration hypothesis remains unproven, but it is certainly compatible with the apparent need for higher weekly clearances with intermittent therapies. Accordingly, it may be appropriate to increase the weekly KTN urea for intermittent PD therapies, such as nightly peritoneal dialysis, as compared to CAPD. For chronic hemodialysis, most centers strive for a weekly KTN urea value at or above 3.0 (2), whereas in CAPD the typical regimen yields a weekly KTN urea between 1.5 and 1.8. There was great interest in kinetic modeling of CAPD clearance prescriptions at the 10th Annual Conference on Peritoneal Dialysis in Dallas, Texas, in February of 1990 (1, 3–6). The focus was on defining adequate peritoneal dialysis and optimizing nutrition. The purpose of this editorial is not to review the pros and cons of modeling dialysis therapy to achieve defined doses of small solute clearances nor to support or refute the peak concentration hypothesis.

The disposition and dynamics of labetalol in patients on dialysis.

The disposition of labetalol was assessed in 16 patients on dialysis after intravenous dosing with 0.7 to 1.0 mg/kg during an interdialytic period and just before hemodialysis (n = 8) and during continuous ambulatory peritoneal dialysis (CAPD) (n = 8). The plasma concentration time data exhibited triexponential decay in all patients. The terminal t 1/2 of labetalol was 12.90 +/- 4.68 hours, the total body clearance was 1198.2 +/- 249.4 ml/min, and the AUC was 921.4 +/- 175.2 ng hr/ml during the interdialytic period. No significant changes were observed in these parameters after dosing with labetalol just before dialysis. The hemodialysis clearance of labetalol was 30.67 +/- 5.49 ml/min, and only 0.189 +/- 0.042 mg of labetalol was removed by hemodialysis. The terminal t 1/2 averaged 13.05 +/- 6.32 hours during CAPD. Steady-state volume of distribution, total body clearance (Clp), and CAPD clearance were 10.39 +/- 2.77 L/kg, 1397.2 +/- 372.3 ml/min, and 1.94 +/- 0.65 ml/min, respectively. The fraction of the dose recovered in the CAPD dialysate during the 72-hour study period was 0.14% +/- 0.09%. The decay of the antihypertensive effect of labetalol was gradual and paralleled the decline in the log plasma concentration. There was a significant correlation between labetalol plasma concentration and the fall in supine diastolic and mean blood pressure after the interdialytic dose and during CAPD. Although labetalol is removed by dialysis, dialysis does not significantly enhance Clp.

Acyclovir Pharmacokinetics in a Patient on Continuous Ambulatory Peritoneal Dialysis

Acyclovir is an effective agent for the treatment of herpes virus infections, however, the pharmacokinetics of the drug are altered in renal failure. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) patient who was immunocompromised and had cutaneous herpes infection. The elimination half-life (17.1 hours) was similar to that reported for end-stage renal disease (ESRD) patients, while the volume of the central compartment (29.6 L/1.73 m2), the steady state volume of distribution (68.1 L/1.73 m2), and the total body clearance (48.3 mL/min/1.73 m2) were greater. The mean CAPD clearance was only 4.4 mL/min, with less than 10% of an administered dose being recovered in the 24-hour dialysate. Further studies are needed to establish a dosing regimen for CAPD patients.

Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of vancomycin were studied in four patients on continuous ambulatory peritoneal dialysis. After a single intravenous infusion of 10 mg/kg of total body weight, multiple blood, urine, and dialysate samples were collected during a 72-h evaluation period. The steady-state volume of distribution was 0.73 +/- 0.07 (mean +/- standard deviation) liters/kg with a beta half-life of 90.2 +/- 24.2 h. The continuous ambulatory peritoneal dialysis clearance of vancomycin was 1.35 +/- 0.35 ml/min, and the serum clearance was 6.4 +/- 1.1 ml/min. Peritoneal dialysate concentrations of vancomycin were rapidly attained after the intravenous infusion and averaged 2.2 +/- 0.7 mg/liter throughout the 72-h observation period. A loading dose of 23 mg/kg followed by a maintenance dose of 17 mg/kg every 7 days should attain and maintain therapeutic serum and dialysate concentrations. More frequent dosing may be necessary for less susceptible organisms.