Trends in anemia at initiation of dialysis in the United States.

BACKGROUND: Anemia almost invariably develops in patients with chronic renal insufficiency (CRI) and is associated with a wide range of complications. The anemia of CRI can be effectively treated with recombinant human erythropoietin (rHuEPO). Recent studies suggest that the management of anemia of CRI is suboptimal in the United States. METHODS: We examined the trends in hematocrit and rHuEPO use among all patients who started chronic dialysis therapy between April 1, 1995, and December 31, 1999, from the End-stage Renal Disease Medical Evidence Form 2728 submitted to the Health Care Financing Administration of the United States. Follow-up data containing hematocrit levels after initiation were obtained from the Medicare Part A institutional outpatient dialysis provider claims for 1990 to 1998 prevalent patients. RESULTS: From June 1995 to June 1999, the mean hematocrit at initiation of dialysis increased from 28.1 to 29.3%. Likewise, the annual percentage of patients receiving pre-dialysis rHuEPO increased from 21.8 to 28.1%. Patients receiving predialysis rHuEPO had a higher mean hematocrit than patients without predialysis rHuEPO. The annual percentage of patients with hematocrit <24% fell 6.6% and the percentage with hematocrit > or =30% increased 9.2%. The trend toward higher hematocrit levels has been consistent across all age, gender, and race categories. Older patients, males, whites, and those who selected peritoneal dialysis had higher hematocrit levels than their counterparts. There were significant geographic differences in the prevalence of predialysis rHuEPO use. CONCLUSION: There has been a slight improvement in the management of anemia of CRI in the United States. However, a considerable fraction of patients still have hematocrit levels that are significantly lower than the currently recommended target. Furthermore, improvement in the management of anemia could result in improved clinical outcomes among patients with CRI.

Hospitalization risks between Renagel phosphate binder treated and non-Renagel treated patients.

AIM: We evaluated 152 sevelamer hydrochloride treated Medicare patients on hemodialysis in a case-controlled study matching 152 randomly selected non-sevelamer hydrochloride treated Medicare patients from the same dialysis facilities and time period. The main outcomes evaluated were the risk of all-cause hospitalization and per-member per-month (PMPM) Medicare expenditures in the follow-up period. PATIENTS AND METHODS: Medicare patients were identified from a total of 195 patients who were included in a long-term safety and efficacy clinical trial evaluating sevelamer hydrochloride [Chertow et al. 1999a]. The average serum calcium-phosphorus product as well as lipid profiles improved in the sevelamer hydrochloride treated group during the trial. Sevelamer treated patients were matched with randomly selected Medicare patients for age, gender, race, diabetic status, and geographic location. Comorbid conditions were characterized and sequential Cox regression models were applied with the outcome being risk of first hospitalization in a 17- month follow-up period. RESULTS: Across all four models, the relative risk of hospitalization was 46% to 54% less in the sevelamer hydrochloride treated group, as compared to the case control group (significant at the p-value 0.03 level). Overall, Medicare expenditures for the control patients per-member per-month were US-$4,745, compared to US-$3,368 in the sevelamer hydrochloride treated patients. CONCLUSION: Sevelamer hydrochloride treated patients had a 50% lower likelihood of hospitalization in the follow-up period after adjustments for the differences in the population. Potential bias may exist between groups because of differences in baseline characteristics that could not be adjusted for within the study design. We feel that to further advance this area, a randomized clinical trial should be performed.

Nephrology pharmaceutical care preceptorship: a programmatic and clinical outcomes assessment.

OBJECTIVE: The University of Pittsburgh Nephrology Pharmaceutical Care Preceptorship (NPCP) program was conceived to acquaint health system pharmacists with the pharmacotherapeutic management of dialysis patients, enhance the delivery of pharmaceutical care, and improve clinical outcomes through the development of specialized professional skills. A survey designed to determine the impact of the NPCP program was sent to all 145 participants of the program. METHODS: The survey, designed to collect demographic information and data about the participants' practice sites, professional activities prior to and after the completion of the program, and markers of disease status, was mailed to all participants in September 1997. The 96 respondents (66.2%) were involved in a wide variety of clinical practices; inpatient management of peritoneal dialysis, hemodialysis, or renal transplant patients were most commonly reported. RESULTS: More than 80% of the participants believed that the educational content of the NPCP program was sufficient to allow them to establish a specialized service for the management of dialysis patients. However, two-thirds would have preferred to have more contact time (an additional 1-2 d) with the preceptorship faculty. The percentage of the pharmacists' time devoted to the provision of pharmaceutical care for dialysis patients almost doubled, from 13.1% to 25.2% (p < 0.001). The components of pharmaceutical care performed by these pharmacists also changed as a result of their completion of the NPCP program. Time devoted to clinical services and the provision of educational programs (inservices) increased significantly, while the time allocated to distributive activities decreased from a mean of 32.4% to 26.4% (almost 20% from baseline). The number of pharmacists who provided some component of pharmaceutical care for ambulatory dialysis patients increased significantly, from 10 to 33, after completion of the program. In the survey given after the preceptorship, almost 70% of these 33 pharmacists self-reported that the mean hematocrit of their ambulatory dialysis patients increased; 45% reported that the epoetin dose was lower. Parenteral iron use was also reported to have increased in 78.8% of the dialysis units, and an increase in serum ferritin and transferrin saturation was observed in 54.5% and 60.6% of the units. respectively. Although far fewer pharmacists (n = 15) initiated a renal osteodystrophy management program, 73.3% of those who did so reported an increase in their patients' compliance with phosphate binder therapy, which was reflected in a drop in serum phosphorous in 40% of the units. CONCLUSIONS: The NPCP program resulted in changes in the professional activities of the participants: fewer distributive activities and increased clinical and educational activities. These significant changes were noted in all areas of outpatient care. Participation in the NPCP program enhanced the delivery of pharmaceutical care to dialysis patients and improved the markers of disease status.

Pain comparison after subcutaneous administration of single-dose formulation versus multidose formulation of epogen in hemodialysis patients.

Subcutaneous (s.c.) injection is an approved route of administration for recombinant human erythropoietin (epoetin alfa). However, pain at the injection site with the single-dose formulation has limited its use. With the recent development of a multidose formulation containing benzyl alcohol as a preservative, anecdotal reports have emerged that suggest this product causes less stinging. Using a randomized, triple-blind, placebo-controlled crossover design, this study compared pain perception, intensity, and duration after s.c. injection with a multidose formulation versus single-dose formulation using visual analogue (VAS) and verbal descriptive pain scales (VDS). Twenty-eight hemodialysis patients received s.c. injections of placebo (normal saline) in one arm and either the multidose or single-dose formulation in the opposite arm. One week later, the subjects again received placebo in one arm and the other epoetin alfa formulation in the opposite arm. The VAS and VDS measurements were obtained at time 0 and then every 5 minutes for a period of 30 minutes. Results showed a statistically significant difference in pain perception between formulations at times 0, 10, and 15 minutes for both the VAS and VDS. In conclusion, there was a significant difference in pain perception between formulations with the multidose formulation causing less pain than the single-dose formulation. However, it should be noted that several patients reported no pain with the single-dose formulation. This indicates that individual patient response could be considered when deciding which formulation to use, although it may be difficult to implement an error-free distribution and administration system using the two different formulations.

Drug therapy in haemodialysis patients. Special considerations in the elderly.

End-stage renal disease (ESRD) is the stage of renal failure at which an individual requires dialysis therapy or a renal transplant to survive. The prevalence of ESRD is disproportionately higher among patients aged > 65 years, and the average age of new ESRD patients is continually rising in the US Medicare population. Medication management in this population is challenging because of the combination of multiple comorbid disease states, a plethora of medications and the added dimension of dialysis therapy, as well as pharmacokinetic and pharmacodynamic changes attributable to the aging process. Cardiovascular disorders such as hypertension, coronary artery disease, congestive heart failure and arrhythmias are common in elderly patients with ESRD, and account for most of the deaths in this population. Constipation is common in patients aged > 65 years, and its incidence is even higher among those receiving dialysis. Pain management is of particular concern because elderly dialysis patients are frequently prescribed inappropriate pain relief regimens. Many healthcare practitioners do not realise that patients with uraemia are at a higher risk of bleeding caused by nonsteroidal anti-inflammatory drugs than are patients with normal renal function. In addition, most practitioners do not appreciate that virtually all opioids (narcotics) and their active metabolites accumulate in patients with renal failure, leading to an increased risk of narcosis. Infectious complications are frequent in the ESRD population, with dialysis access infections and pneumonia being the 2 most common infections seen in hospitalized patients receiving dialysis treatment. The establishment of vaccination programmes for the prevention of hepatitis B, influenza and pneumococcal infections is important because of the increased risk of these disease in this population. Unfortunately, these high-risk patients display, in general, a decreased immunogenic response to vaccinations. This article addresses some of the practical issues that surround the medication management or prevention of these particular diseases in elderly patients undergoing haemodialysis. Specifically, we discuss the pharmacokinetic and pharmacodynamic changes that occur with specific medications in such patients. Drug dialysability is also discussed.

Accuracy of technicians versus pharmacists in checking syringes prepared for a dialysis program.

The accuracy of pharmacy technicians versus pharmacists in checking drug doses prepared in syringes for a dialysis program was studied. Three pharmacy technicians from the pharmacy of a regional kidney disease program in Minnesota participated in the study after completing a training program and after common preparation errors had been identified by pharmacists. From November 1995 to April 1996, the technicians used labels printed from a database of pharmacist-verified orders to prepare and label i.v. syringes. Four medications were used-epoetin alfa, calcitriol, heparin prepared from beef lung, and heparin prepared from porcine intestinal mucosa. Each syringe was checked by one of nine pharmacists for accuracy of dose and medication, and all errors were recorded. The technicians checked syringes prepared by other technicians and also recorded errors. Accuracy rates (percentages of syringes correctly evaluated) for pharmacists and technicians were compared. A total of 10,608 syringes were checked. Accuracy rates for pharmacists and pharmacy technicians were 99.86% and 99.83%, respectively. Accuracy rates in checking syringes did not differ significantly between pharmacists and technicians in this study setting.

Hypoprothrombinemia associated with cefmetazole.

OBJECTIVE: To report a case of hypoprothrombinemia associated with the use of cefmetazole sodium, define patients at risk for this adverse effect, and identify options to prevent this problem. CASE SUMMARY: A malnourished patient with endstage renal disease received cefmetazole following a below-the-knee amputation of the right leg. Three days later, a prothrombin time (PT) and an international normalized ratio (INR) were obtained and were markedly elevated from baseline; however, the patient had no clinical symptoms of bleeding. Cefmetazole was discontinued. Vitamin K and fresh frozen plasma were administered. The PT and INR normalized within 24 hours and remained normal throughout the remainder of hospitalization. DISCUSSION: The incidence of hypoprothrombinemia associated with cefmetazole reported in the literature is conflicting and not consistent. There are three proposed mechanisms of cephalosporin-associated hypoprothrombinemia, two of which involve the N-methylthiotetrazole (NMTT) chain. The most plausible mechanism is NMTT inhibition of vitamin K epoxide reductase in the liver. Patients at an increased risk for this adverse event include those with low vitamin K stores, specifically patients who are malnourished, with low albumin concentrations and poor food intake. The elderly and patients with liver or renal dysfunction are examples of populations at risk. CONCLUSIONS: Hypoprothrombinemia may occur with cephalosporins and is especially problematic with those containing an NMTT side chain. Clinicians need to identify patients at risk for developing antibiotic-associated hypoprothrombinemia, monitor them closely, and give vitamin K as prophylaxis accordingly.

Randomized cross-over study of adverse reactions and cost implications of intravenous push compared with infusion of iron dextran in hemodialysis patients.

In many dialysis centers, iron dextran is administered by intravenous infusion rather than intravenous push (the method of administration recommended in the package insert) as a possible, but unproven, means to reduce side effects. This study was performed to determine whether there is a difference in adverse reactions between these two methods. Ten iron-deficient hemodialysis patients participated in a randomized, cross-over study of iron dextran 100 mg administered by intravenous push over 2 minutes (undiluted) or as a 30-minute intravenous infusion during the first hour of hemodialysis. Patients received a total of four doses (two by each method during four separate dialysis sessions). Blood pressure and heart rate were monitored pre-dose and at frequent intervals throughout the hemodialysis session following the dose. Patients completed adverse event surveys before and 60 minutes after the dose and prior to the next hemodialysis session. Blood pressure, heart rate, and survey data were analyzed using a Wilcoxon analysis (P

Acetazolamide toxicity and pharmacokinetics in patients receiving hemodialysis.

Acetazolamide-induced central nervous system toxicity occurred in two patients undergoing hemodialysis. Symptoms of toxicity included fatigue, lethargy, and confusion, which resolved several days after discontinuing acetazolamide. Pharmacokinetic studies showed markedly elevated serum concentrations of the drug during the period of toxicity, which decreased at a slower rate compared with that reported in patients with normal renal function. The effect of hemodialysis on acetazolamide clearance was quantified. The agent should be avoided in patients receiving dialysis unless the dosage is reduced and serum concentration monitoring can be performed in a timely manner. These patients should be monitored closely for central nervous system toxicity if acetazolamide is given.

Clinical pharmacokinetics of antibiotics in patients with impaired renal function.

Many antibiotics are eliminated renally and dosage adjustments are commonly made in patients with renal insufficiency. This is a critical review of antibiotic pharmacokinetics in patients with various degrees of renal function. Detailed information regarding pharmacokinetic alterations with specific antibiotics or antibiotic classes has been compiled and tabulated. From pharmacokinetic evidence, recommendations for dosage adjustments of antibiotics are supplied. The criteria used for assigning rating levels to specific pharmacokinetic articles as well as the grading system for dosage adjustments are outlined. In addition, a basic review of pharmacokinetic alterations in renal failure and factors affecting the removal of drugs by haemodialysis is included.

Teicoplanin measurement in patients with renal failure: comparison of fluorescence polarization immunoassay, microbiological assay, and high-performance liquid chromatographic assay.

Characterization of antibiotic pharmacokinetics in patients with renal insufficiency may be complicated by interfering substances within the assay. We compared three different assays for teicoplanin in serum and dialysate of 10 hemodialysis and six continuous ambulatory peritoneal dialysis (CAPD) patients. The microbiological assay (micro) had a within-run and between-run coefficient of variation (% CV) of less than 7.5% for concentrations ranging from 0.2 to 96 micrograms/ml. The high-performance liquid chromatographic assay (HPLC) within- and between-run %CV was less than 8% for concentrations ranging from 1 to 80 micrograms/ml. The fluorescence polarization immunoassay (FPIA) within- and between-run %CV was less than 7% for concentrations ranging from 5 to 100 micrograms/ml. In serum of hemodialysis patients FPIA results were slightly higher than HPLC results: FPIA = 1.11 HPLC + 2.37 (r = 0.975, n = 202), and FPIA concentrations in serum were also slightly higher than those measured by micro (FPIA = 1.21 micro - 1.57, r = 0.972, n = 161). The HPLC and micro serum results were also comparable in hemodialysis patients: micro = 0.92 HPLC + 2.89, r = 0.953, n = 160. However, in CAPD patients micro results were lower than HPLC results in serum (micro = 0.82 HPLC + 0.49, r = 0.981, n = 262). In peritoneal dialysate, HPLC values were approximately 60% of the micro values. Thus, FPIA may be the optimal technique for therapeutic monitoring of teicoplanin in the clinical setting due to its simplicity, specificity, and good correlation to HPLC and micro.