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Background Information about residual renal function (RRF) and outcomes associated with practices of diuretic use in patients with end-stage renal disease is not available worldwide. Methods Diuretic use was investigated in 16,420 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients selected from nationally representative facilities on 3 continents. Logistic regressions were used to investigate associations between diuretic use and patient characteristics. Outcomes of interdialytic weight gain, increased serum potassium and phosphorus levels, and odds of retaining RRF after 1 year were investigated. Cox regression was used to analyze the association between mortality and diuretic use. Results Facility diuretic use varied substantially from 0% to 83.9% of patients. Diuretic use decreased sharply after the start of dialysis therapy. Loop diuretic use ranged from 9.2% in the United States to 21.3% in Europe, whereas use within 90 days of starting dialysis therapy ranged from 25.0% in the United States to 47.6% in Japan. Diuretic use was associated with lower interdialytic weight gain and lower odds of hyperkalemia (potassium > 6.0 mmol/L). Patients with RRF on diuretic therapy had almost twice the odds of retaining RRF after 1 year in the study versus patients not on diuretic therapy. Patients administered diuretics had a 7% lower all-cause mortality risk (P = 0.12) and 14% lower cardiac-specific mortality risk (P = 0.03) versus patients not administered diuretics. Conclusion Variation exists in facility practices of diuretic use. In patients with RRF, there may be benefit associated with continuing diuretic use rather than automatically discontinuing diuretic therapy at dialysis initiation.

Background: Medication-related problems are common in hemodialysis (HD) patients. These patients often require 12 medications to treat 5 to 6 comorbid conditions. Medication-related problem research reports cannot be generalized to the entire HD population because data are obtained from single centers and limited numbers of patients. We conducted a pooled analysis to gain additional insight into the frequency, type, and severity of medication-related problems and extrapolated the data to the entire US HD population. Methods: Articles were identified through a MEDLINE search (1962 to March 2004). Seven studies were included in the analysis. Medication-related problems were categorized into the following 9 categories: indication without drug therapy, drug without indication, improper drug selection, subtherapeutic dosage, overdosage, adverse drug reaction, drug interaction, failure to receive drug, and inappropriate laboratory monitoring. A medication-related problem appearance rate was determined. Results: We identified 1,593 medication-related problems in 395 patients (51.2% men; age, 52.4 ± 8.2 years; 42.7% with diabetes). The most common medication-related problems found were inappropriate laboratory monitoring (23.5%) and indication without drug therapy (16.9%). Dosing errors accounted for 20.4% of medication-related problems (subtherapeutic dosage, 11.2%; overdosage, 9.2%). The medication-related problem appearance rate was 5.75e−0.37x, where x equals number of months of follow-up (P = 0.02). Conclusion: HD patients experience ongoing medication-related problems. Reduction in medication-related problems in dialysis patients may improve quality of life and result in decreased morbidity and mortality. Pharmacists are uniquely trained to detect and manage medication-related problems. Pharmacists should be an integral member of the dialysis health care team.

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Ceftazidime is currently recommended as an alternative first-line agent in the treatment of peritonitis and for Pseudomonas peritonitis. The pharmacokinetics of intermittent intraperitoneal (i.p.) ceftazidime have been poorly characterized. This study was designed to characterize the pharmacokinetic disposition of a single dose of ceftazidime in anuric and non-anuric CAPD patients, over 48 hours. This was a prospective, open label, pharmacokinetic study. The study was conducted in an independent, outpatient dialysis center. Ten volunteer continuous ambulatory peritoneal dialysis (CAPD) patients with and without residual renal function, no peritonitis or antibiotics in the previous 4 weeks, and on CAPD for at least 2 months were recruited. Patients received a single dose of i.p. ceftazidime (15 mg/kg) in the first daytime exchange over a 6-hour dwell, after an overnight dwell. Serum, urine, and dialysate were collected over a 48-hour period. A high-pressure liquid chromatography (HPLC) assay was used to analyze ceftazidime in these samples. Pharmacokinetic parameters were calculated. Six of the 10 patients were non-anuric with a mean residual renal creatinine clearance of 2.9 +/- 1.6 mL/min. The mean +/- SD bioavailability was 72% +/- 14%, and the volume of distribution was 0.34 +/- 0.08 L/kg. The mean serum elimination half-life of 22 +/- 5 hours. The peritoneal clearance was 5.74 +/- 1.6 mL/min. No difference was detected between anuric and nonanuric patients. Mean plasma and dialysate concentrations at 24 hours were 24 +/- 6 microg/mL and 18 +/- 7 microg/mL, respectively, and were 12.0 +/- 3.6 microg/mL and 7.4 +/- 3.1 microg/mL at 48 hours, respectively. Once-daily i.p. dosing of ceftazidime achieves serum and dialysate levels greater than the MIC of sensitive organisms over 48 hours.

The HCFA ESRD Core Indicators Project is designed to assess several key indicators of care in peritoneal dialysis patients, including anemia management. Information on hematocrit levels, epoetin alfa dosing, estimates of iron stores, and iron therapy as obtained in a national sample of 1,219 peritoneal dialysis patients are described. The average hematocrit was 32.8% +/- 3.8%, and severe anemia (hematocrit < 25%) occurred in 1.4% of PD patients. The mean weekly epoetin alfa dose was 134.6 U/kg. In general, there was an inverse relationship between hematocrit and epoetin alfa doses. Most (83%) of PD patients received iron therapy, with only 8% of patients receiving intravenous iron. The mean serum ferritin was 303 ng/mL, with 64% of patients having a ferritin greater than 100 ng/mL. The mean transferrin saturation was 28%, with 60% of patients having a value of less than 20%. There was an inverse relationship between serum ferritin levels and hematocrit but no relationship between hematocrit and transferrin. It is concluded that there could be improvement in the epoetin alfa and iron management in many patients.