Intraperitoneal administration of recombinant human erythropoietin.

OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable.     

蔗糖铁注射液治疗腹膜透析患者肾性贫血的临床研究

目的:比较静脉用蔗糖铁与口服琥珀酸亚铁治疗腹膜透析患者肾性贫血的疗效与安全性。方法:57例患者分为静脉组22例,口服组35例;两组均应用重组人红细胞生成素120~150 u/kg,1次/周,皮下注射;静脉组加用蔗糖铁100 mg稀释于100 mL生理盐水中静脉滴注,2~3次/周;口服组加用琥珀亚酸铁口服,200 mg/次,3次/d。结果:治疗后血红蛋白、红细胞压积、网织红细胞均较治疗前显著升高;静脉组血红蛋白、红细胞压积升高比口服组显著(P<0.01),血红蛋白上升速度明显快于口服组;静脉组血清铁、铁蛋白、转铁蛋白饱和度均明显升高(P<0.01);口服组铁蛋白治疗后较治疗前显著升高(P<0.05),但血清铁、转铁蛋白饱和度治疗前后比较差异无统计学意义;静脉组血清铁、铁蛋白、转铁蛋白饱和度治疗前后与口服组比较差异有统计学意义(P<0.01)。肝功能、肾功能等指标治疗前后差异无统计学意义,静脉组未发现1例不良反应,口服组4例出现不良反应。结论:静脉用铁剂蔗糖铁治疗腹膜透析患者肾性贫血安全、有效。     

Teicoplanin pharmacokinetics and bioavailability during peritoneal dialysis

The pharmacokinetics of teicoplanin in serum and dialysate were examined in a crossover study after intravenous and intraperitoneal administration of a 3 mg/kg dose to five anuric patients who were undergoing continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were obtained for 30 and 15 days, respectively, and were assayed microbiologically. The principal pharmacokinetic parameters after intravenous administration were as follows: total body clearance, 2.76 +/- 1.08 ml/min; elimination half-life, 377 +/- 109 hours; volume of distribution at steady state, 1.04 +/- 0.18 L/kg. Only 9% +/- 6% of the intravenous dose was recovered in the dialysate and the net peritoneal clearance was 0.25 +/- 0.21 ml/min. Bioavailability values, which were assessed by use of three methods after intraperitoneal administration and while dialysate was retained in the peritoneal cavity for 5 hours (dwell time), were 0.77 +/- 0.21, 0.78 +/- 0.05, and 0.76 +/- 0.08. Changes in bioavailability with dwell time were also examined. A dosing guide, which accounts for changes in bioavailability with dwell time, is presented.     

Efficient monthly subcutaneous administration of darbepoetin in stable CAPD patients.

BACKGROUND: Although subcutaneous administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients is a widely accepted recommendation, the lowest possible frequency of an efficient dosing regimen remains controversial. Darbepoetin alpha, a new erythropoiesis-stimulating protein with a threefold longer serum half-life compared with rHuEPO, has greater in vivo potency and can be administered less frequently to obtain the same biological response. This study assessed the efficacy of darbepoetin administered once monthly in the treatment of anemia in CAPD patients. PATIENTS AND METHODS: In this single-center, prospective cohort study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 +/- 14.1 years; mean duration on peritoneal dialysis 31.6 +/- 13 months) maintained average hemoglobin and hematocrit levels of 12.09 +/- 1.29 g/dL and 37.29% +/- 3.58%, respectively, while receiving a mean weekly maintenance dose of epoetin alfa of 129 IU/kg. These same patients were assigned to receive the equivalent weekly darbepoetin dose once monthly for 24 consecutive weeks. Hematological response, iron status (transferrin saturation, serum ferritin levels), C-reactive protein (CRP), and the patients' biochemical profiles were evaluated monthly. RESULTS: During the monthly administration of darbepoetin, mean serum levels of Hb and Hct were 12.17 +/- 1.28 g/dL and 37.1% +/- 1.19% respectively. No statistically significant difference was apparent between the previous and monthly dosing values (12.09 +/- 1.29 vs 12.17 +/- 1.28 g/dL, p = 0.769, and 37.29% +/- 3.58% vs 37.1% +/- 1.19%, p = 0.752). Transferrin saturation levels as well as serum ferritin levels also remained unchanged (30.4% +/- 8.6% vs 30.1% +/- 9.4%, NS, and 556 +/- 212 vs 621 +/- 234 ng/mL, respectively, NS). CONCLUSION: These results indicate that darbepoetin alfa can be effectively given subcutaneously at monthly intervals for the treatment of anemia in stable CAPD patients. However, more studies are needed to validate the long-term efficacy of this monthly subcutaneous administration.     

Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis

The effect of long-term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD). RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg-1 body weight. After 3 months of rHuEPO haemoglobin increased from 77.7 +/- 3.2 to 112.7 +/- 5.6 g l-1 (P less than 0.03), haematocrit rose from 22.8 +/- 1.2 to 30.3 +/- 1.7% (P less than 0.01). A consistent decrease in ferritin concentration was observed during this time (P less than 0.05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes. The rHuEPO-induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 +/- 28 ml 4 h-1 dwell time to 273 +/- 45 ml 4 h-1 (P less than 0.03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 +/- 43 ml 4 h-1, P less than 0.05). The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P less than 0.05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P less than 0.05). No severe adverse effects of rHuEPO treatment could be observed. The present results demonstrate that long-term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration.     

Ceftizoxime elimination kinetics in continuous ambulatory peritoneal dialysis

We investigated the kinetics of ceftizoxime, a beta-lactamase stable cephalosporin, in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 500-mg or 1-gm dose was injected IV, or a 500-mg dose was given intraperitoneally in the CAPD fluid during a 6-hr dwell time. The ceftizoxime (500 mg) serum kinetic parameters were as follows: peak concentrations, 21 to 46 mg/l; volume of distribution, 0.27 l/kg; elimination rate constant, 0.0784 hr-1; plasma clearance, 1.66 l/kg hr-1; and t1/2, 10.2 hr. The t1/2 after 1 gm was 12 hr. Dialysate ceftizoxime concentrations rose rapidly between 0.25 and 2 hr and slowly over the next 4 hr, but only 4.04 +/- 1.8 and 7.4 +/- 2.9 mg ceftizoxime/hr was eliminated by the peritoneal route over a 6-hr dwell time after 500 mg or 1 gm IV. This represents only 4% to 5% of the dose. After intraperitoneal instillation, the antibiotic appeared in the serum within 15 min in all four subjects, and the peak serum concentrations ranged from 12 to 19.8 mg/l (mean +/- SD = 16.4 +/- 3.3) between 5 and 6 hr. Approximately 78% of ceftizoxime was absorbed from the peritoneal dialysis fluid during a single 6-hr dwell time. Rate constant for absorption, ka, was 0.3959 hr-1 and absorption t1/2 was 1.75 hr (as calculated by the residual equation). These data suggest that ceftizoxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of ceftizoxime in CAPD fluid alone may permit rapid absorption to reach therapeutic serum concentrations.     

Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in continuous ambulatory peritoneal dialysis (CAPD) patients

The single dose pharmacokinetics of recombinant human erythropoietin (r-HuEPO) were compared in six continuous ambulatory peritoneal dialysis (CAPD) patients after intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) administration of 300 U/kg. Intravenous administration gave results close to those obtained in hemodialysis patients, with a half-life of 11.2 h and a volume of distribution of 5.0% of body weight. After subcutaneous administration, the serum concentration rose slowly to plateau between 24 and 36 h, the area under the serum concentration vs. time curve from 6 to 72 h being 18.2% of that after intravenous administration. After intraperitoneal administration, the serum concentration was even lower, the area under the curve from 0 to 24 h was between 2.5 and 3.6% of that after intravenous administration, and 80% of the administered dose was recovered in the first peritoneal effluent after a 4-h dwell time.     

Erythropoietin in continuous ambulatory peritoneal dialysis: experience with subcutaneous administration.

Experience in the use of subcutaneous erythropoietin (EPO) in 32 continuous ambulatory peritoneal dialysis (CAPD) patients is presented. All patients were treated with oral iron supplements. The total and mean +/- SD durations of EPO treatment were 466 weeks and 14.6 +/- 10.1 weeks respectively. Twenty-two patients started treatment with normal or elevated iron stores; 10 had an initial iron saturation less than 20%. The initial hematocrit was 23.8 +/- 3.7%. Thirteen patients reached a steady-state hematocrit by the end of the study period, when the mean +/- SD hematocrit for all 32 patients was 34.1 +/- 3.6%. All patients responded to EPO. The initial dose of EPO was 147.1 +/- 53.8 U/kg/week. Maintenance dose was 72 +/- 36 U/kg/week.     

The effect of recombinant erythropoietin on the early hematocrit rise after CAPD initiation.

OBJECTIVE: To determine if the simultaneous initiation of continuous ambulatory peritoneal dialysis (CAPD) and Erythropoietin therapy masks the hematocrit (Hct) rise that frequently follows the initiation of CAPD alone. DESIGN: Single-center retrospective analysis. SETTING: University multidisciplinary dialysis program. PATIENTS: All adult CAPD patients with a Hct less than or equal to 28% whose nephrologist felt they would benefit from Erythropoietin therapy and who did not have technical reasons for exclusion (N = 25). INTERVENTIONS: Eight patients began CAPD and Erythropoietin alfa subcutaneously, at a dose of 128 +/- 9 (X +/- SEM) units/kg/week at the same time. Seventeen patients already on CAPD for 8.7 +/- 1.5 months received Erythropoietin alfa subcutaneously at a dose of 124 +/- 7 units/kg/week. Pre-epoetin Hct's were similar. MAIN OUTCOME MEASURES: Hematocrit changes, status of iron stores, incidence of peritonitis, and dosage of Erythropoietin. RESULTS: In 1 month, the group initiating both therapies simultaneously demonstrated a mean Hct rise of 7.6 +/- 0.5% while established CAPD patients receiving Erythropoietin increased their Hct by only 4.7 +/- 1.0% (p less than .03). Iron status could not explain this difference. Peritonitis did not appear to dampen the Hct rise following Erythropoietin in either CAPD group. By 2 months after Erythropoietin, the differences were less apparent. CONCLUSION: The early rapid increase in Hct is probably the combined effect of CAPD and Erythropoietin and should not be attributed to Erythropoietin alone. When comparing responses to Erythropoietin from patients on different therapies, the timing of dialysis initiation and Erythropoietin initiation must be considered.     

Pharmacokinetics of intraperitoneal cefepime in automated peritoneal dialysis.

OBJECTIVE: This study determined the pharmacokinetics of intraperitoneal (IP) cefepime in automated peritoneal dialysis (APD) patients. DESIGN AND METHODS: A prospective pharmacokinetic study was performed in 6 noninfected adult APD patients. All patients were administered a single IP dose of cefepime (15 mg/kg) over a 6-hour dwell. Patients then underwent a fixed APD regimen consisting of the first 6-hour dwell, followed by an 8-hour dialysate-free period and a subsequent series of 3 overnight APD exchanges. Blood and dialysate samples were collected at t = 0, 1, 2, 4, 6 (end of dwell), and 24 hours. Any urine produced during the study period was collected. Cefepime concentrations in serum, dialysate, and urine were determined by liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated assuming a mono-exponential model. RESULTS: One hour after IP administration, serum cefepime levels exceeded the minimum inhibitory concentration (8 microg/mL) for susceptible organisms. The mean serum and dialysate concentrations at 24 hours were 15.8 +/- 3.6 and 6.2 +/- 2.3 microg/mL respectively. Bioavailability was 84.3% +/- 6.2%, volume of distribution 0.34 +/- 0.07 L/kg, and serum half-life 13.8 +/- 3.2 hours. Total, peritoneal, and renal clearances were 16.5 +/- 4.4, 4.3 +/- 0.7, and 3.5 +/- 2.5 mL/minute, respectively. CONCLUSIONS: IP cefepime dosed at 15 mg/kg resulted in adequate serum concentrations in APD patients at 24 hours post dose. Pharmacokinetic predictions suggest that most APD and CAPD patients would achieve adequate serum cefepime concentrations if treated with standard doses of 1000 mg given IP once daily. Patients using APD regimens different from that used in this study, anuric patients, and those with significant residual renal function may require a more individualized approach.     

Moxalactam kinetics during continuous ambulatory peritoneal dialysis after intraperitoneal administration.

Moxalactam kinetics during continuous ambulatory peritoneal dialysis (CAPD) was followed in eight patients after a single intraperitoneal dose of 1 g. Approximately 60% of the dose was absorbed after a dwell time of 4 h. Dialysis solutions were exchanged at 4-h intervals with an overnight dwell of 8 h. The mean (+/- standard deviation) elimination half-life was 13.2 +/- 2.9 h, and the mean apparent volume of distribution was 0.22 +/- 0.08 liters/kg. Mean total clearance was 11.5 +/- 2.4 ml/min, with a mean dialysis clearance of 2.3 +/- 0.5 ml/min. The maximum concentration in plasma ranged from 24.5 to 54.1 micrograms/ml. Moxalactam concentrations in the peritoneal dialysis fluid were above 80 micrograms/ml during the first exchange and above 2 micrograms/ml for a further three exchanges. A suggested intraperitoneal dose regimen for patients undergoing CAPD is 1 g initially, followed by 15 to 25% of the recommended dose for normal patients given at the same time intervals, or 30 to 50% of the recommended dose at twice the usual intervals. Moxalactam is suggested for initial treatment of peritonitis in CAPD patients who do not have ready access to the antibiotic of choice.     

Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis

We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.     

Pharmacokinetics of intermittent intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To investigate the pharmacokinetic parameters of intermittent intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective nonrandomized open study. SETTING: CAPD outpatient clinic in Albany, New York. PATIENTS: Seven volunteer CAPD patients without peritonitis.Three of the patients were nonanuric while 4 were anuric. INTERVENTIONS: Cefazolin (15 mg/kg total body weight) was given to each patient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1,2,3,6 (end of the first antibiotic-containing dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period. RESULTS: The mean+/-SD amount of cefazolin dose absorbed from the dialysate after the 6-hour dwell was 69.7%+/-8.0% of the administered dose. The cefazolin absorption rate constant from dialysate to serum was 0.21+/-0.1/hr (absorption half-life 3.5+/-0.8 hr). The mean serum concentrations reached at 24 and 48 hours were 52.4+/-3.7 mg/L and 30.3+/-5.9 mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and 48 hours were 15.1+/-3.4 mg/L and 7.9+/-1.4 mg/L, respectively.The cefazolin serum elimination rate constant was 0.02+/-0.01/hr (elimination half-life 31.5+/-8.8 hr). The total cefazolin body clearance was 3.4+/-0.6 ml/min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6+/-0.4 ml/min. The peritoneal clearance of cefazolin was 1.0+/-0.3 mL/min. The systemic volume of distribution of cefazolin was 0.2+/-0.05 L/kg. No statistical difference was detected in pharmacokinetic parameters between anuric and nonanuric patients, although this may be due to the small number of patients in each group. CONCLUSION: A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration levels greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution is warranted in extrapolation of dosing recommendations to patients who maintain a significant degree of residual renal function.     

Amikacin pharmacokinetics during continuous ambulatory peritoneal dialysis.

The pharmacokinetics of amikacin were investigated in five stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Each patient was studied after the administration of 7.5 mg of amikacin per kg by both the intravenous (i.v.) and intraperitoneal (i.p.) route, allowing a 1-month washout period between doses. No differences in amikacin half-life, volume of distribution, total body clearance, or time-averaged peritoneal clearance were noted between the two routes of administration. After a 5-h dwell period, bioavailability as calculated by the area under the curve for i.p. amikacin was 53 +/- 14.0%. Amikacin pharmacokinetics parallel those of other aminoglycosides in CAPD patients when the drug is administered either i.v. or i.p. Single loading doses of amikacin administered i.v. to uninfected CAPD patients provided therapeutic serum and dialysate levels for many aerobic gram-negative organisms for up to 72 h. Because of the variability of absorption of i.p. administered amikacin, single i.p. doses are not recommended.     

Multiple-dose-kinetics of ofloxacin after intraperitoneal application in CAPD patients.

Pharmacokinetics of ofloxacin in plasma and peritoneal fluid were studied in 11 patients on continuous ambulatory peritoneal dialysis (CAPD). Seven patients without peritonitis received 20 mg ofloxacin added to 2L dialysate i.p. every 6 h for one day only, while 4 patients with acute peritonitis were treated with this same dosage every 4 h for 3 days, then every 6 h for the next 7 days. Ofloxacin concentrations in plasma and dialysate were determined by HPLC. After i.p. drug application there was a rapid elimination of ofloxacin from dialysate, this being significantly faster in patients with peritonitis as compared to those without. Likewise, the total amount lost from the first bag after a 3 h dwell was higher in the peritonitis group (84.7 +/- 1.5%; mean +/- SEM) than in the non-peritonitis group (75.6 +/- 2.1%). Twenty-four h after start of ofloxacin treatment, the mean peritoneal fluid concentrations at the end of each exchange studied were all above 3 mg/L. In patients with peritonitis, plasma concentrations of ofloxacin rose to 0.94 +/- 0.05 mg/L after 24 h reaching a Cmax of 1.8 +/- 0.2 mg/L after a tmax of 84 +/- 23 h. Intraperitoneal administration of ofloxacin was well tolerated, and no local or systemic adverse events were observed. Peritonitis episodes that were caused by Staphylococcus epidermidis (3) and by E. coli (1) were cured in all patients.     

Results of peritoneal equilibration test during treatment with polyglucose dialysis solution.

BACKGROUND: Results of peritoneal equilibration test (PET) suggest prolonged effect of polyglucose dialysis solution (PG-DS) on peritoneal permeability. OBJECTIVES: An evaluation of dialysate-to-plasma ratio (D/P) of urea, DIP creatinine, and D/D0 glucose (ratio of dialysate glucose at designated dwell time to dialysate glucose at 0 dwell time), and mass transfer area coefficients (KBD) of these solutes in PET before introduction, during administration, and after discontinuation of PG-DS hi patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Single-center prospective study with PG-DS; retrospective selection of the control group. SETTING: Peritoneal dialysis unit in a university hospital. PATIENTS: Fourteen patients (11 males; age 45.1 +/- 8.5 years) treated with CAPD for 17.5 +/- 9.9 months. 7.5% PG-DS was used for the overnight exchange. After discontinuation of the PG-DS, standard dialysis solutions, as previously used, were reintroduced. The control group was selected to match both CAPO duration and peritoneal permeability of the patients in the PG-DS group at the start of the study. METHODS: Standard PET was carried out at 1.6 +/- 0.8 months before the introduction of PG-DS (study period I, n = 14), after 1.2 +/- 0.6 months' use of PG-DS (study period II, n = 14), after 4.4 +/- 0.8 months' use of PG-DS (study period Ill, n = 11), after 8.8 +/- 2.2 months' use of PG-DS (study period IV, n = 9), and at 2.0 +/- 0.6 months after PG-DS discontinuation (study period V, n = 11). Patients in the control group underwent PET at similar time intervals (control periods I-V). RESULTS: In the PG-DS group, a tendency toward increased peritoneal permeability for urea and creatinine was shown during the consecutive study periods. D/D0 glucose was significantly higher only in the PET performed during use of PG-DS (periods II-IV) compared to results obtained in period I. In the control group, both D/P and KBD of both urea and creatinine remained unchanged, but K90 glucose was higher in the first 2 hours of the PET in control period V compared to respective values in control period III. CONCLUSION: Changes in peritoneal permeability are observed In CAPD patients treated with PG-DS. These changes may be at least partially related to the administration of polyglucose.     

A pharmacodynamic model of erythropoietin therapy for uremic anemia.

Fifty-seven patients receiving chronic high-flux hemodialysis began receiving recombinant alpha-human erythropoietin (rHuEPO). The mean initial rHuEPO dose used in 54 evaluable patients was 9963 +/- 4364 U/week; the final dose was 8972 +/- 4058 U/week. Treatment over a mean period of 154 +/- 40 days (84 to 224 days) resulted in an average increase in hematocrit from 24.7% +/- 3.7% to 32.5% +/- 4.4%. We present a model for these data that describes changes in hematocrit during rHuEPO therapy and that allows simultaneous estimation of red blood cell lifespan and rHuEPO-induced increases in red blood cell production rate. Analysis of the hematocrit values of the patients with the model, by use of NONMEM, a computer program for analysis of population data, reveals a nonlinear dose-response relationship with large interindividual variability (coefficient of variation) of about 50%. The estimated mean red blood cell lifespan is 64 days, with interindividual variability of about 30% (coefficient of variation). The intraindividual random variability in hematocrit about its prediction is +/- 5% of the prediction. For clinical dose adjustment, we present a method that uses only simple calculations.     

Hepatic subcapsular steatosis as a complication associated with intraperitoneal insulin treatment in diabetic peritoneal dialysis patients.

OBJECTIVES: The aim of this study was to evaluate hepatic subcapsular steatosis (HSS) and its association with clinical parameters in nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients and in diabetic CAPD patients receiving intraperitoneal (IP) or subcutaneous (SC) insulin. DESIGN: Cross-sectional study. SETTING: A tertiary-care university hospital. PATIENTS: 28 CAPD patients (17 males and 11 females; mean age 53.5 +/- 14 years; mean CAPD duration 22.8 +/- 9 months) were included in the study. 14 patients had type II diabetes mellitus and 14 were nondiabetics. In the diabetic group, 8 patients were receiving IP insulin and 6 were receiving SC insulin. OUTCOME MEASURES: HSS was diagnosed on computed tomography without contrast administration. Other data collected were body mass index (BMI), weekly Kt/V, peritoneal equilibration test (PET) results, daily insulin dosage, duration of diabetes mellitus, duration of insulin treatment, dialysate glucose load, and serum findings for alanine aminotransferase, aspartate aminotransferase, albumin, and lipid profiles. RESULTS: HSS was detected in 5 of the 8 diabetics who were receiving IP insulin. None of the diabetics receiving SC insulin and none of the nondiabetic patients exhibited HSS. Daily insulin dosage [108 (95 - 108.5) vs 54 (36 - 72) U/day, p = 0.02], BMI [31 (30.5 - 36) vs 26.6 (26 - 30) kg/m2, p = 0.02], serum triglyceride level [194 (184 - 505) vs 69 (61 - 82) mg/dL, p = 0.04], and PET creatinine levels [D/P2 creat: 0.67 (0.54 - 0.74) vs 0.50 (0.50 - 0.56), p = 0.05; D/P4 creat: 0.75 (0.64 - 0.86) vs 0.60 (0.59 - 0.62), p = 0.02] were higher in diabetic patients receiving IP insulin who had HSS than in those who did not have HSS. PET glucose levels [D0/D2 glu: 0.40 (0.37 - 0.45) vs 0.50 (0.48 - 0.51), p = 0.03; D0/D4 glu: 0.36 (0.26 - 0.38) vs 0.44 (0.38 - 0.48), p = 0.04] were lower in diabetic patients receiving IP insulin who had HSS than in those who did not have HSS. CONCLUSIONS: Our results suggest that IP insulin plays a more important role in the pathogenesis of HSS than glucose levels in diabetic CAPD patients. They also indicate that HSS is associated with higher daily insulin requirement, obesity, hypertriglyceridemia, and high peritoneal transport rate in diabetic CAPD patients receiving IP insulin.     

Moxalactam kinetics during chronic ambulatory peritoneal dialysis

Moxalactam kinetics in renal failure were followed in eight patients undergoing chronic ambulatory peritoneal dialysis (CAPD) after a single 1-gm IV infusion. Elimination t 1/2 was 16.7 +/- 2.1 hr, with an apparent volume of distribution of 0.21 +/- 0.01 l/kg and plasma clearance of 10.6 +/- 2 ml/min. In 24 hr, 17.4 +/- 3.1% of the dose was present in the dialysis fluids, and 14.6 +/- 5.7% was excreted in the urine. Renal and peritoneal clearance values were thus 2.3 +/- 1.1 and 2.7 +/- 0.5 ml/min. Peritoneal concentrations were high (22.7 +/- 2.2 micrograms/ml). A recommended dosage schedule is proposed on the basis of moxalactam kinetics during CAPD.     

Intravenous iron sucrose in peritoneal dialysis patients with renal anemia.

OBJECTIVE: To explore the safety and efficacy of intravenous (IV) iron sucrose in maintenance peritoneal dialysis (PD). DESIGN: Randomized, controlled, parallel-group single-center trial. SETTING: Blood Purification Center of Chaoyang, Beijing Capital University of Medical Science, China. METHODS: 46 patients on PD were involved in this trial. 26 patients received IV iron sucrose (200 mg iron) once per week for 4 weeks then once every other week for a further 4 weeks. The other 20 patients received oral ferrous succinate, 200 mg three times per day, for 8 weeks. Hemoglobin, hematocrit, serum ferritin (SF) level, and transferrin saturation (TSAT) were assessed at baseline and then again after 2, 4, and 8 weeks of treatment. RESULTS: There were no differences between the IV and oral groups in terms of sex, age, duration of PD, mean dialysate dosage per day, erythropoietin dosage per week, or hematological parameters at baseline. After 4 and 8 weeks of treatment, mean Hb and Hct were significantly increased in the IV group and were also significantly higher than those in the oral group. Levels of SF and TSAT were also significantly increased in the IV group, and significantly higher than in the oral group. After 8 weeks, the response rate in the IV group was 94.8%, which was significantly higher than that in the oral group. The mean erythropoietin dose was significantly lower in the IV group than in the oral group. Hb, Hct, SF, and TSAT levels were maintained between 4 and 8 weeks in the IV group despite the decrease in dose frequency. There were no adverse events with IV iron. Eight patients in the oral group had adverse gastrointestinal effects. CONCLUSION: IV iron sucrose is safe in PD patients. It increases Hb levels and serum iron parameters more effectively than oral iron; it is well tolerated and can permit reductions in the required dose of erythropoietin.