Vancomycin disposition following intraperitoneal administration in children receiving peritoneal dialysis.

BACKGROUND: Little information is available on the disposition of vancomycin during chronic peritoneal dialysis (PD) in children. The primary objective of this study was to investigate the disposition of vancomycin following intraperitoneal (IP) administration in children receiving short-dwell [e.g., automated PD (APD)] and long-dwell [e.g., continuous ambulatory PD (CAPD)] PD. METHODS: A 6-hour exchange containing vancomycin 500 mg/L, using an exchange volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90-minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were obtained and analyzed for vancomycin concentration by high-pressure liquid chromatography. Pharmacokinetic parameters were computed using noncompartmental methods. RESULTS: The bioavailability of vancomycin during a 6-hour IP exchange was 70% +/- 5%, resulting in a delivered dose of 12.0 +/- 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3 +/- 7.2 microg/mL. Total body vancomycin clearance measured 10.72 +/- 4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD measured 2.78 +/- 1.08 mL/min/1.73 m2 BSA and accounted for 29% +/- 11% of total vancomycin clearance. Dialysis clearance during long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 +/- 1.04 and 3.09 +/- 1.28 mL/min/1.73 m2 BSA, accounting for 25% +/- 13% and 32% +/- 12% of total body clearance respectively. CONCLUSIONS: Intraperitoneal absorption and dialysis clearance of vancomycin in children receiving PD are similar to those reported in adult dialysis patients. In contrast, total body clearance of vancomycin appears to be increased and the elimination half-life decreased in children, due to increased elimination by non-renal nondialysis routes. For intermittent IP vancomycin therapy in children with peritonitis, an IP load containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100 mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from day 2 until the end of treatment will maintain a vancomycin dialysate concentration of >4 microg/mL.     

No significant differences in peritoneal fluid handling in children using PH-neutral or acidic solutions.

OBJECTIVES: Differences in peritoneal fluid handling in the acute setting can be expected if children are converted to pH-neutral dialysis solutions because conventional acidic solutions exert toxic effects on peritoneal mesothelial cells and microcirculation. Peritoneal fluid kinetics was therefore investigated with both types of solutions in a group of children. DESIGN: Peritoneal equilibration tests (PETs) were performed in 12 patients [mean age 70 months, mean time on peritoneal dialysis (PD) 18 months] using a pH-neutral PD fluid (Physioneal 3.86%; Baxter Ltd, Castlebar, Ireland) and dextran 70 as a volume marker. The results of these PETs were compared to those of a historic group of 12 children (mean age 75 months, mean time on PD 17 months). SETTING: Pediatric dialysis unit in a tertiary institute. PATIENTS: Stable pediatric PD patients. MAIN OUTCOME MEASURES: Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate-to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose. RESULTS: TCUF and lymphatic absorption were not different between the two groups. There was also no significant difference in small solute clearance measured by D/P ratio for urea and creatinine and D(t)/D(0) ratio for glucose. CONCLUSION: Peritoneal fluid kinetics is not significantly altered if pH-neutral dialysis solutions are applied compared to acidic solutions. An altered TCUF, as is hypothetically possible using an acidic solution, was not established.     

Physiological properties of the peritoneum in an adult peritoneal dialysis population over a three-year period.

OBJECTIVES: To describe the physiological properties of the peritoneal membrane in adult patients treated with peritoneal dialysis (PD) and to analyze the effects of patient characteristics and time. DESIGN: Observational study. SETTING: Department of Nephrology at the Sahlgrenska University Hospital. METHOD: Peritoneal function was analyzed by the Personal Dialysis Capacity (PDC) test, based on the three-pore theory of capillary transport. The functional PDC variables are absorption, large-pore flow, and the area parameter (A0/deltax), which determines the diffusion of small solutes. The ultra-filtration (UF) coefficient is determined mainly by A0/deltax. PATIENTS: All patients (n = 280) who had at least one PDC test done between September 1990 and August 1999. RESULTS: In 249 patients examined soon after start of PD, area was 19000 (SD 7100) cm2/cm/1.73 m2, large-pore flow 0.112 (SD 0.052) mL/min/1.73 m2, and the UF coefficient 0.071 (SD 0.032) mL/minute/mmHg/1.73 m2. Absorption was 1.54 (SD +2.64, -0.97) mL/min/1.73 m2. Large-pore flow was greater in patients with severe comorbidity than in patients with fewercomorbid conditions. Elderly patients had a lower UF coefficient than did younger patients (p < 0.05). Repeated PDC tests were performed in 208 patients during a mean observation time of 18.4 months. There was a slight increase in the slope of the area-versus-time curve of 54 cm2/cm/1.73 m2 per month (approximately 10% after 3 years, p < 0.01); all other parameters remained constant. CONCLUSION: Patient characteristics have an impact on peritoneal performance already at the start of dialysis. Peritoneal function can remain essentially stable during medium long-term PD.     

Evaluation of intraperitoneal pressure and the effect of different osmotic agents on intraperitoneal pressure in children.

OBJECTIVES: To establish intraperitoneal pressure (IPP) in a relatively large pediatric study group and to study the effects of a 3.86% glucose solution and a 7.5% icodextrin solution on IPP during a 4-hour dwell. DESIGN: IPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m2 with a 1.36% glucose solution. The influence of dialysis solutions was obtained by performing two 4-hour peritoneal equilibration tests (PETs) with 3.86% glucose and 7.5% icodextrin as test solution, using an IPV of 1200 mL/m2 and dextran 70 as volume marker. IPP was measured at two consecutive time points (t = 0 and t = 240 minutes). Transcapillary ultrafiltration, net ultrafiltration, and marker clearance were calculated. PATIENTS: IPP was established in 30 patients with median age of 4.5 years (range 1.0 - 14.9 years). Influence of dialysis solutions on IPP was studied in 9 children with median age of 4.2 years (range 1.7 - 10.9 years) and median treatment period of 12 months (range 5.6 - 122.3 months). RESULTS: Mean IPP was 12.0 +/- 6.5 cm H2O. Significant relations were found between the change in IPP and transcapillary ultrafiltration and body surface area during the PET with 3.86% glucose. No relations were seen during the PET with icodextrin. CONCLUSIONS: IPP was established in a large pediatric study group and was similar to previously published values of IPP in a small number of patients. Differences in fluid kinetics have different effects on the change in IPP during a 4-hour dwell period.     

Indexed glomerular filtration rate as a function of age and body size

The conventional way in which to scale or index a measurement of glomerular filtration rate (GFR) is to express it in relation to body surface area (BSA). However, BSA may not be appropriate for infants and children because, as individuals increase in size, their relative BSA decreases. Several other whole-body variables have been suggested as alternatives, including extracellular fluid volume (vECF). The purpose of the present study was to compare BSA and vECF as variables against which to index GFR, and in particular to look at this comparison in children versus adults. A total of 130 patients (age range 1-80 years; 40 patients <12 years) undergoing clinically indicated routine measurement of GFR using the bolus-injection single-compartment technique were included in the study. GFR was measured as the plasma clearance of [(51)Cr]EDTA as assessed from three peripheral venous blood samples taken between 2 and 4 h after injection of [(51)Cr]EDTA. Volume of distribution (V(d)) was obtained by extrapolation of the clearance curve to zero time. GFR was scaled to a BSA of 1.73 m(2). GFR and GFR/1.73 m(2) were corrected to account for the assumption of a single compartment. The rate constant of the exponential between 2 and 4 h was also corrected to give GFR/litre ECF. GFR and GFR/1.73 m(2) were both divided by GFR/litre ECF, to give vECF and vECF/1.73 m(2) respectively. Weight per unit BSA increases as a linear function of BSA. vECF is always less than V(d), on average by about 30%. vECF increased as an exponential function of BSA and as a linear function of body weight. vECF/70 kg body weight was higher in children (16. 2+/-3 litres) than adults (13.4+/-2.3 litres), but vECF/1.73 m(2) was lower in children (9.7+/-1.7 litres) compared with adults (12. 4+/-2 litres). vECV/1.73 m(2) increased as a function of both age and BSA, but vECF/kg decreased. GFR/12.5 litres vECF was higher than GFR/1.73 m(2) in children, but these values were similar in adults, with the ratio of these two forms of indexed GFR falling significantly with both age and BSA. Although this was not a normal population, but one with a wide range of renal function, GFR/vECF showed a strong inverse association with age, whereas for GFR/BSA the association was weak. In conclusion, these data provide further evidence that vECF is more valid physiologically for indexing GFR than is BSA, especially in children. Nevertheless, a GFR measurement in a child should ideally be expressed as a percentage of normal for that child's age. However, such normal values are not yet available.     

Comparison between bicarbonate/lactate and standard lactate dialysis solution in peritoneal transport and ultrafiltration: a prospective, crossover single-dwell study.

OBJECTIVE: It has been proposed that biocompatible bicarbonate/lactate based (Bic/Lac), physiologic-pH peritoneal dialysis (PD) solutions will be beneficial in long-term PD. However, we do not yet have detailed knowledge concerning the comparative physiology of buffer transport for these new solutions and their impact on underlying peritoneal transport of solutes and ultrafiltration (UF). The purpose of this study was to investigate the profile of buffer handling and peritoneal membrane transport characteristics during a single dwell of the new Bic/Lac-based versus standard lactate-based (Lac) PD solution. METHODS: In this prospective crossover study, we compared a 25 mmol/L bicarbonate/15 mmol/L lactate buffered, physiologic pH, low glucose degradation product (GDP) solution (Physioneal; Baxter Healthcare, McGaw Park, Illinois, USA) with a standard lactate buffered, acidic pH, conventional solution (Dianeal; Baxter). 18 patients underwent two peritoneal equilibration tests (PETs) with 2.5% Dianeal and 2.5% Physioneal separated by 1 week. Buffer transport, mass transfer area coefficients (MTACs), solute transport, and UF were determined for the two PETs. All bags were weighed by a nurse before instillation and after drainage to assess the net UF in each dwell. RESULTS: 18 patients that met the inclusion criteria were enrolled in this study. Whereas intraperitoneal pH remained constant at 7.52 +/- 0.11 throughout the dwell with the Bic/Lac solution, pH was still in the acidic range with the Lac solution after 1 hour (7.29 +/- 0.13, p < 0.001); this difference disappeared after the second hour of dwell. The MTACs for creatinine (10.68 +/- 3.66 vs 10.73 +/- 2.96 mL/minute/1.73 m(2), p > 0.05) and urea (27.94 +/- 10.50 vs 27.62 +/- 6.95 mL/min/1.73 m(2), p > 0.05), for Bic/Lac versus Lac respectively, did not differ between these two solutions; transport of glucose and other solutes was also similar. However, after a 4-hour dwell with Bic/Lac solution, net UF was significantly lower than that observed with Lac solution (274.2 +/- 223.3 mL vs 366.1 +/- 217.3 mL, p = 0.026). CONCLUSIONS: Compared to standard Lac-based solution, Bic/Lac based, pH neutral, low-GDP solution avoids intraperitoneal acidity. Peritoneal mass transport kinetics are similar for small solutes. Net UF is significantly lower with Bic/Lac solution; the mechanism for this is unclear.     

Intraperitoneal calcitriol in infants on peritoneal dialysis.

BACKGROUND: Calcitriol has long been used as the main therapy in renal osteodystrophy, but the efficacy of the oral route is not always as high as expected. OBJECTIVE: To asses the safety and efficacy of intraperitoneal calcitriol in infants undergoing peritoneal dialysis (PD). PATIENTS AND METHODS: PD patients on oral calcitriol therapy, with serum parathyroid hormone (PTH) >1000 pg/mL during the previous 3 months of treatment, were switched to intraperitoneal calcitriol therapy, 1 microg twice per week. Dose was increased to 1 microg three times per week if PTH remained >1000 pg/mL, and was later readjusted. Target PTH was 200-300 pg/mL according DOQI guidelines. STATISTICS: All results are expressed as mean +/- SE. The Wilcoxon signed rank test was used to evaluate differences in measurements for each pair of values. The confidence interval for differences between population medians was 96.9%. A p value less than 0.05 was considered significant. RESULTS: Six male children, mean age 17 +/- 3.86 months, completed a 12-month follow-up. Mean pretreatment PTH was 1654 +/- 209 pg/mL. Mean PTH at months 0, 3, 6, 9, and 12 was 1448 +/- 439*, 1277 +/- 723, 910 +/- 704, 582 +/- 282*, and 465 +/- 224* pg/mL, respectively (*p < 0.05). Twelve hypercalcemic and 10 hyperphosphatemic episodes were successfully treated. CONCLUSION: Infants on PD who fail to respond to oral calcitriol therapy can be safely treated with intraperitoneal administration of active vitamin D.     

Predictors of decline of residual renal function in new peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to prospectively evaluate the risk factors for decline of residual renal function (RRF) in an incident peritoneal dialysis (PD) population. DESIGN: Prospective observational study of an incident PD cohort at a single center. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 146 consecutive patients commencing PD at the Princess Alexandra Hospital between 1 August 1995 and 1 July 2001 (mean age 54.8 +/- 1.4 years, 42% male, 34% diabetic). Patients with failed renal transplants (n = 26) were excluded. MAIN MEASUREMENTS: Timed urine collections (n = 642) were performed initially and at 6-month intervals thereafter to measure RRF. The development of anuria was also prospectively recorded. RESULTS: The mean (+/- SD) follow-up period was 20.5 +/- 14.8 months. The median slope of RRF decline was -0.05 mL/minute/month/1.73 m2. Using binary logistic regression, it was shown that the 50% of patients with more rapid RRF loss (< -0.05 mL/min/month/1.73 m2) were more likely to have had a higher initial RRF at commencement of PD [adjusted odds ratio (AOR) 1.83, 95% confidence interval (CI) 1.39-2.40] and a higher baseline dialysate/ plasma creatinine ratio at 4 hours (D/P creat; AOR 44.6, 95% CI 1.05-1900). On multivariate Cox proportional hazards model analysis, time from commencement of PD to development of anuria was independently predicted by baseline RRF [adjusted hazard ratio (HR) 0.81, 95% CI 0.60-0.81], D/P creat (HR 2.87, 95% CI 2.06-82.3), body surface area (HR 6.23, 95% CI 1.53-25.5), dietary protein intake (HR 2.87, 95% CI 1.06-7.78), and diabetes mellitus (HR 1.65, 95% CI 1.00-2.72). Decline of RRF was independent of age, gender, dialysis modality, urgency of initiation of dialysis, smoking, vascular disease, blood pressure, medications (including angiotensin-converting enzyme inhibitors), duration of follow-up, and peritonitis rate. CONCLUSIONS:The results of this study suggest that high baseline RRF and high D/P creat ratio are risk factors for rapid loss of RRF. Moreover, a shorter time to the onset of anuria is independently predicted by low baseline RRF, increased body surface area, high dietary protein intake, and diabetes mellitus. Such at-risk patients should be closely monitored for early signs of inadequate dialysis.     

Suitable dialytic indicators for pediatric peritoneal dialysis patients: the alternative to creatinine clearance.

OBJECTIVE: Owing to the discord between body weight and body surface area (BSA), creatinine clearance (CCr) is predisposed to be small in pediatric patients on peritoneal dialysis (PD). Alternatively, Kt/V creatinine (Kt/V creat), which is normalized to total body water (TBW) rather than BSA, could be a better dialytic indicator. In this study, the efficiency of dialysis and the nutritional status of pediatric patients on chronic PD were examined, and the utility of dialytic indicators was evaluated. PATIENTS AND METHODS: 49 patients under 20 years old, in stable condition, and on PD were analyzed. Weekly total Kt/V of urea (Kt/V urea), CCr, Kt/V creat, and normalized protein equivalent of nitrogen appearance (nPNA) were measured for all patients and for patients under 6 years old. The target value was 2.0/week for Kt/V urea and 60 L/ week/1.73 m2 for CCr, as recommended by the Kidney Disease Outcomes Quality Initiative guidelines. The target value for Kt/V creat was set as 1.52/week, using a male model with a height of 170 cm and a body weight of 65 kg. RESULTS: The mean values of delivered Kt/V urea, CCr, Kt/V creat, and nPNA (and proportion of patients that achieved each target value) for all patients were 2.25 +/- 0.57/ week (67.4%), 53.8 +/- 19.3 L/week1/.73 m2 (26.5%), 1.83 +/- 0.73/ week (65.3%), and 1.11 +/- 0.42 g/day, respectively. The values for patients under 6 years old were 2.38 +/- 0.26/week (90.0%), 45.9 +/- 12.8 L/week/1.73 m2 (10.0%), 1.94 +/- 0.51/week (90.0%), and 1.52 +/- 0.67 g/day, respectively. Stepwise multiple regression analyses revealed that the relationship between CCr and Kt/V urea was affected by the patient's age. CONCLUSIONS: Our pediatric patients achieved the recommended target value of Kt/V urea. At the same time, the nPNA results reflected the patient's status well. However, CCr appeared to be inappropriate as an indicator for patients under 6 years old. Kt/V creat is suggested to be a better dialytic indicator for these patients.     

Intraperitoneal cefazolin and ceftazidime effects on human peritoneal mesothelial cell release of cancer antigen-125

BACKGROUND: Intraperitoneal (IP) cefazolin and ceftazidime are recommended as empiric treatment for peritoneal dialysis (PD)-associated peritonitis. Human peritoneal mesothelial cells (HPMCs) may be affected by high IP cefazolin and ceftazidime concentrations. Peritoneal dialysate cancer antigen-125 (CA-125) appearance rate can be used to measure HPMC damage. OBJECTIVE: To determine whether IP cefazolin and ceftazidime increase peritoneal CA-125 appearance rate. METHODS: The study consisted of 2 phases. In phase I, no antibiotic was administered, and in phase II, patients received IP cefazolin and ceftazidime (15 mg/kg rounded to nearest 100 mg). Phase II occurred immediately after phase I. Each phase used a 4-hour dwell time with 2 L of dextrose 2.5% dialysate. Dialysate samples were collected at 0, 0.5, 1, 2, and 4 hours during each phase. Samples were assayed for CA-125, and CA-125 appearance rate was calculated. RESULTS: Thirteen patients were recruited (7 men; aged 44.0 +/-16.0 y). The mean +/- SD (range) CA-125 dialysate concentration after phases I and II were 6.6 +/- 3.7 U/mL (2.3-15.0) and 6.4 +/-3.8 U/mL (1.6-13.8), respectively (p = 0.46). The CA-125 appearance rate after phases I and II were 51.9 +/- 31.3 U/min/1.73 m(2) (13.8-113.0) and 50.5 +/- 32.9 U/min/1.73 m(2) (11.0-104.0), respectively (p = 0.57). The slopes of the regression lines of CA-125 appearance rate were not significantly different between phases I and II. CONCLUSIONS: These findings demonstrate that concurrently administered IP cefazolin and ceftazidime have no effect on HPMC release of CA-125 in non-infected PD patients.     

Multiexponential elimination of gentamicin. A kinetic study during development

The long-term disposition of gentamicin (up to 100-240 h) was studied in 13 premature newborns (33 weeks mean gestational age) and in 7 infants and children (1 month to 8 years). The data fitted bi- or triexponential curves with terminal half-lives averaging 51 and 37 h. Newborns showed lower values of body clearance, central compartment and steady state volumes of distribution than infants and children (respectively, 12.8 vs. 50.4 ml/min/1.73 m2, 9.03 vs. 17.5 liters/1.73 m2, and 15.7 vs. 35.5 liters/1.73 m2). The ratio between the amount of gentamicin predicted at steady state in the tissue compartment and in the total body was also significantly lower in newborns than in the older group (0.4 vs. 0.52). These data provide pharmacokinetic demonstration of an age dependence in gentamicin tissue distribution and excretion during the early stages of human development.     

Changes in peritoneal equilibration test values during long-term peritoneal dialysis in peritonitis-free children.

Little is known about the changes in peritoneal equilibration test (PET) values in children on long-term peritoneal dialysis (PD). In the present study, a PET was carried out every 6 months in 39 children (mean age 8.8 +/- 5.5 years) undergoing PD for 6 to 85 months (mean 36.9 +/- 23.1 months). Patients experiencing peritonitis were excluded. Both D/P creatinine (dialysate-to-plasma ratio of creatinine at 4 hours) and D/D0 glucose (ratio of dialysate glucose at 4 hours' dwell time to dialysis glucose at 0 dwell time) were measured 195 times in this series of patients. No remarkable change was found for D/P creatinine or D/D0 glucose during the first 24 months of PD but thereafter, D/P creatinine increased gradually and D/D0 glucose decreased gradually. Mean D/P creatinine increased significantly after the first 24 months of PD: from 0.66 +/- 0.12 during the first 24 months, to 0.70 +/- 0.09 after 25 months and more of PD (p = 0.0051). Mean D/D0 glucose decreased significantly after 24 months of PD: from 0.42 +/- 0.09 during the first 24 months, to 0.38 +/- 0.08 after 25 months and more of PD (p = 0.0015). The most significant change for both D/P creatinine and D/D0 glucose occurred after 24 months of PD. It seems reasonable to consider the mean PET values at 24 months of PD as the standard PET values.     

Dyslipidemia in peritoneal dialysis--relation to dialytic variables.

OBJECTIVE: To investigate whether the specific lipoprotein (LP) abnormalities of peritoneal dialysis (PD) are associated with functional variables of this mode of dialysis. DESIGN: A survey of the LP profile in relation to peritoneal dialysis capacity (PDC) variables.The LP profile was compared to that of a group of age- and sex-matched controls. SETTING: The Peritoneal Dialysis Unit at Sahlgrenska University Hospital in Gothenburg, Sweden. PATIENTS: Twenty-two nondiabetic PD patients (5 women, 17 men) who had been on PD for at least 6 months. MAIN OUTCOME MEASURES: The LP profile included plasma lipids, apolipoproteins (Apo), and individual ApoA- and ApoB-containing LP. The PDC measurement determined peritoneal glucose uptake, protein losses, effective peritoneal surface area, and total weekly creatinine clearance. RESULTS: The patients had been on PD for 6 to 48 months (mean 15.3 months) and had a total weekly creatinine clearance of 69.7+/-13.3 L/1.73 m2 body surface area, an average peritoneal glucose uptake corresponding to 446+/-162 kcal/24 hour, and a protein loss of 8.1+/-2.5 g/24 hr. The patients had significantly higher total cholesterol (7.1 mmol/L),VLDL-cholesterol (1.0 mmol/L), LDL-cholesterol (4.7 mmol/L), and triglyceride levels (2.5 mmol/L); whereas the HDL-cholesterol level (1.2 mmol/L) was significantly lower than in controls. The PD patients had increased levels of ApoB-containing LPs, both of the cholesterol-rich LP-B and of the triglyceride-rich LP-B complex, reflected in higher plasma concentrations of ApoB, ApoC-III, and ApoE. Furthermore, they had significantly lower levels of LP-A-I:A-II, as well as of ApoA-I and ApoA-II. The LP-A-I:A-II and ApoA-II levels correlated inversely with the duration of PD treatment (r = 0.54, p < 0.01 and r = 0.52, p < 0.05, respectively).The ApoA-II level was inversely correlated with the peritoneal surface area (r = 0.53, p < 0.05). There were no other correlations between LP variables and PDC variables, nor did any of the LP variables correlate with peritoneal glucose uptake or protein losses. CONCLUSION: The proatherogenic lipoprotein profile of patients on PD is characterized by increased concentrations of cholesterol-rich and triglyceride-rich ApoB-containing LPs. While the duration of treatment appears to have some influence on the development of this type of dyslipidemia, the pathophysiological links to the dialysis mode must be further explored.     

Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients.

BACKGROUND: Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (i.v.) piperacillin in automated PD patients. PATIENTS AND METHODS: Eight patients (3 males, 5 females) were recruited and received a single i.v. dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on cycler), and end of dwells 4-5 (off cycler) for a 24-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m2. RESULTS: The patients were 49.5 +/- 10.1 years of age (mean +/- SD) and had been receiving PD for a median of 3 months (range 2-66 months). Dwell times were 2.25 +/- 0.06 hours on cycler and 7.26 +/- 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 +/- 0.39 hr, off cycler 4.39 +/- 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 +/- 0.41 hr, off cycler 2.54 +/- 1.48 hr; p = 0.19). Piperacillin total CL (CL(T)) was 31.29 +/- 6.02 mL/minute. Renal CL (CL(R)) and PD CL (CL(PD)) accounted for 8.8% and 16.8% of CL(T); CL(R) correlated well with GFR (CL(R) = 0.86 GFR + 0.1; p < 0.00003). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 microg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that i.v. piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. CONCLUSION: The current i.v. piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended.     

Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients.

The pharmacokinetics of intravenous (i.v.) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single i.v. dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1-3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (CI) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 +/- 9.9 years of age (mean +/- SD)] who had received PD for a median 3.5 months (range 2-66 months) were studied. Dwell times were 2.3 +/- 0.1 hours on cycler and 7.3 +/- 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 +/- 5.2 hr vs 62.8 +/- 33.0 hr; p < 0.001). Vancomycin total CI (CI(T)) was 7.4 +/- 2.0 mL/min. Renal CI (CI(R)) and PD CI (CI(PD)) accounted for 23.6% and 28.0% of CI(T). respectively. CI(R) correlated with GFR (CI(R) = 0.90 GFR - 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 micro/mL) for the first cycler and the second ambulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg i.p. thereafter (i.e., once daily) in APD patients.     

Impact of fill volume on peritoneal clearances and cytokine appearance in peritoneal dialysis.

BACKGROUND: Current adequacy guidelines for peritoneal dialysis encourage the use of large fill volumes for the attainment of small solute clearance targets. These guidelines have influenced clinical practice in a significant way, and adoption of higher fill volumes has become common in North America. Several studies, however, have challenged the relevance of increasing small solute clearance; this practice may result in untoward consequences in patients. OBJECTIVE: The present study was designed to explore the relationship between dialysate volume and the clearance of different sized molecules, fluid dynamics, and appearance of peritoneal cytokines. METHODS: Thirteen adult prevalent patients on continuous ambulatory peritoneal dialysis were studied. Three different dialysate volumes (2.0, 2.5, and 3.0 L) were infused on consecutive days in a random order. Several measurements of peritoneal fluid dynamics (intraperitoneal pressure, net ultrafiltration, fluid absorption), solute clearances (urea, creatinine, beta2-microglobulin, albumin, IgG, and transferrin), and appearance of interleukin-6 and tumor necrosis factor alpha (TNFalpha) were assessed. RESULTS: Increase in dialysate fill volume (from 2 to 2.5 to 3 L) was examined in relationship to body surface area (BSA). The dialysate volume/BSA (DV/BSA) ratio increased from 1262 to 1566 to 1871 mL/m2 on 2.0, 2.5, and 3.0 L dialysate volumes, respectively. In parallel, diastolic blood pressure increased from 82.7 +/- 8.8 to 87.0 +/- 9.5 to 92 +/- 8.3 mmHg (p < 0.05). Net ultrafiltration rate also increased, from 0.46 +/- 0.48 to 0.72 +/- 0.42 to 0.97 +/- 0.49 mL/minute (p < 0.01), despite a concomitant increase in fluid absorption, from 1.05 +/- 0.34 to 1.21 +/- 0.40 to 1.56 +/- 0.22 mL/min (p < 0.01). Urea peritoneal clearance increased from 8.27 +/- 0.68 to 9.92 +/- 1.6 to 12.98 +/- 4.03 mL/min (p < 0.01); creatinine peritoneal clearance increased from 6.69 +/- 1.01 to 7.64 +/- 1.12 to 8.69 +/- 1.76 mL/min (p < 0.01). Clearance of the other measured molecules did not change. Appearance of interleukin-6 increased 17% and 43% (p < 0.01), and TNFalpha appearance increased 14% and 50% (p < 0.01) when dialysate volumes of 2.5 and 3.0 L were used, compared with 2.0 L. CONCLUSIONS: These results show that, with higher values of DV/BSA ratio, small solute peritoneal clearance is increased, but clearances of large molecules remain unchanged. With the use of higher volumes, fluid absorption rate and the appearance of proinflammatory cytokines in the dialysate are increased.     

Fibrin glue used successfully in peritoneal dialysis catheter leakage in children.

BACKGROUND: Acute renal failure in infants and small children is generally treated with peritoneal dialysis (PD). Dialysis has to be started immediately after catheter implantation. Early dialysate leakage can complicate the effectiveness of dialysis. Fibrin glue applied to the external part of the tunnel may stop dialysate leakage and eliminate the need for surgical intervention. The use of fibrin glue in the treatment of PD catheter leakage in children was studied. METHODS: Fibrin glue was used in 8 children (age 0.8 - 57 months) on PD in whom dialysate leakage was seen during the first 24 to 48 hours after catheter insertion.The dialysis volume initially administered was 20 mL/kg body weight. Fibrin glue (1 mL) was applied to the external part of the subcutaneous catheter tunnel through the exit site, as close to the cuff as possible. The occurrence of dialysate leakage and complications such as exit-site or tunnel infection and peritonitis were evaluated. RESULTS: Nine single-cuff straight Tenckhoff catheters were implanted in 8 children. In 5 cases, no subcutaneous tunnel was created. One child had catheter replacement due to obstruction of the catheter; on both occasions, catheter leakage was seen and treated with fibrin glue. In all 8 patients, no relapse of dialysate leakage was seen after application of the fibrin glue. During the time of PD, exit-site infections, tunnel infections, and peritonitis did not occur. CONCLUSION: Fibrin glue is a successful, simple, and safe substance for the treatment of peritoneal dialysate leakage in infants and small children with acute renal failure treated with PD.     

Peritoneal loss of growth hormone in children on automated peritoneal dialysis.

OBJECTIVE: To provide quantitative data regarding the daily dialytic loss of growth hormone (GH) in children on peritoneal dialysis (PD). DESIGN: Prospective study involving 24-hour dialysate collections on 3 consecutive days in patients with and without recombinant human GH (rhGH) treatment. SETTING: Single-center outpatient PD program. PATIENTS: Twenty-six children undergoing automated PD (APD): 6 with and 20 without daily rhGH. MAIN OUTCOME MEASURES: Daily peritoneal losses of GH, alpha1-, beta2-microglobulin, transferrin, and albumin. RESULTS: The mean (+/-SEM) daily dialytic GH loss was 2.18+/-0.62 microg/1.73 m2 per day in rhGH-treated patients and 0.42+/-0.28 microg/1.73 m2 per day in untreated patients, (p < 0.05). The intraindividual coefficient of variation of daily GH loss was 65%. The peritoneal loss of GH was positively correlated with that of beta2-microglobulin (r = 0.77, p < 0.001) and alpha1-microglobulin (r = 0.51, p < 0.01). The variability in beta2-microglobulin and alpha1-microglobulin elimination, together with the use of rhGH, explained 66% of the total variability of daily GH excretion. In patients without rhGH therapy, the daily peritoneal GH loss was approximately 0.05% of the estimated daily endogenous production rate based on previous estimates in children with end-stage renal failure. In patients on rhGH therapy, less than 0.1% of the injected rhGH dose was eliminated by dialysis. CONCLUSION: Peritoneal losses of GH in children on APD account only for a minute fraction of endogenous metabolic clearance, and do not explain the variability of the rhGH treatment response. The assessment of dialytic GH elimination may be used to estimate time-integrated mean plasma GH concentrations, and to monitor rhGH treatment compliance.     

Peritoneal homocysteine clearance is inefficient in peritoneal dialysis patients.

OBJECTIVES: To investigate the degree and the determinants of peritoneal homocysteine (Hcy) clearance and to compare measured Hcy clearance with the Hcy clearance predicted based on molecular weight (MW). DESIGN: Cross-sectional observational analysis. SETTING: Tertiary care institutional dialysis center. PATIENTS: Sixty-five stable peritoneal dialysis (PD) patients. OUTCOME MEASURES: Fasting blood and 24-hour pooled dialysate effluents were collected for determination of peritoneal clearances of Hcy (CpHcy), urea (CpUr), and creatinine (CpCr). The dialysate-to-plasma creatinine ratio at 4 hours (D/P Cr 4 h) and levels of red cell folate, B12, ferritin, and C-reactive protein (CRP) were measured concurrently. Observed CpHcy was compared with predicted clearance, based on Hcy plasma protein binding and the relative molecular weights of Hcy, urea, and creatinine. RESULTS: Plasma concentrations of Hcy averaged 24.6 +/- 1.1 micromol/L and were elevated above the upper limit of normal in 59 (91%) patients. The mean dialysate concentration of Hcy was 2.9 +/- 0.3 micromol/L, equating to a daily peritoneal elimination of 34.6 +/- 3.6 micromol. Observed CpHcy was closely approximated by predicted CpHcy (8.7 +/- 0.6 L/week/1.73 m2 vs 9.0 +/- 0.3 L/week/1.73 m2 respectively, p = 0.55). Patients maintained on automated PD (n = 5) had a CpHcy similar to that of patients treated with continuous ambulatory peritoneal dialysis (8.9 +/- 1.0 L/week/1.73 m2 vs 8.7 +/- 0.6 L/week/1.73 m2, p = 0.92). The CpHcy was significantly correlated with C-reactive protein (CRP), D/P creatinine, CpUr, CpCr, and peritoneal protein loss, but not with plasma Hcy, albumin, B12, ferritin, age, dialysis duration, peritonitis episodes, or daily dialysate effluent volume. By multivariate analysis, the only variables that remained significant independent predictors of CpHcy were CRP and D/P Cr 4 h. High and high-average transporters had a higher CpHcy than low and low-average transporters (9.7 +/- 0.8 L/week/1.73 m2 vs 7.0 +/- 0.7 L/week/1.73 m2, p < 0.05), despite comparably elevated plasma Hcy concentrations [25.2 +/- 1.5 micromol/L vs 23.4 +/- 1.6 micromol/L, p = nonsignificant (NS)]. CONCLUSIONS: Elevated plasma concentrations of Hcy are not efficiently reduced by PD. The relatively low peritoneal clearance of Hcy is largely accounted for by a high degree of plasma protein binding and is significantly influenced by peritoneal membrane permeability.     

Methodological issues in assessing the incidence of peritoneal dialysis-associated peritonitis in children.

OBJECTIVES: To evaluate the distribution of peritonitis incidence and assess the usefulness of patient-specific peritonitis rates in children. DESIGN: 49 children on automated peritoneal dialysis (PD) followed during a 2-year observation period. SETTING: Single-center, academic children's hospital. PATIENTS: 49 children aged 2 months to 18 years; 24 prevalent, 25 incident during the observation period. Cumulative observation time was 639 patient-months. MAIN OUTCOME MEASURES: Cohort-specific peritonitis incidence, median patient-specific peritonitis incidence, mean peritonitis incidence by gamma-Poisson (negative binomial) modeling, peritonitis-free survival by Kaplan-Meier life-table analysis. RESULTS: 68 new peritonitis episodes and 21 relapses occurred in 27 patients.The distribution of patient-specific peritonitis incidence was bimodal, with a large group experiencing no or very few episodes, and another cluster around 1 episode per 6-9 months. Overall cohort-specific peritonitis incidence was 1.28, median subject-specific incidence 0.99, and mean incidence according to negative binomial modeling 1.04 (95% confidence interval 1.02-1.06) episodes per patient-year. Median peritonitis-free survival time was 6.9 months. In those patients who developed peritonitis, subject-specific peritonitis incidence was inversely correlated with patient age (r = -0.42, p < 0.05) and duration of chronic PD at last observation (r = -0.42, p < 0.05). CONCLUSIONS: Since the distribution of peritonitis in children is non-Gaussian, the average risk of peritonitis is more accurately expressed by the median of the individual subject-specific peritonitis rates or by the mean incidence estimate obtained by the negative binomial distribution model. The assignment of a personal peritonitis risk to each patient permits risk factor analysis by routine statistical methods, even in smaller populations.