Amy Barton Pai

Estimation of creatinine clearance in morbidly obese patients

PURPOSE Estimates of creatinine clearance (CL(cr)) based on equations and various body-size descriptors were compared with 24-hour measured CL(cr) values in morbidly obese patients. METHODS Patients age 18-75 years with a body mass index (BMI) of >/=40 kg/m(2) with stable serum creatinine values were enrolled. Covariates known to contribute to alteration in CL(cr) were used to exclude patients. Twenty-four-hour urine collection was performed to measure CL(cr). Bioelectric impedance analysis was used to estimate fat-free weight (FFW). Glomerular filtration rate was estimated using the four-variable Modification of Diet in Renal Disease (MDRD4) equation. CL(cr) was estimated using the Cockcroft-Gault and Salazar-Corcoran methods using total body weight (TBW). Body-size descriptors, such as ideal body weight (IBW), adjusted body weight (ABW), and lean body weight (LBW), and FFW were substituted in the Cockcroft-Gault equation to generate additional estimates of CL(cr). RESULTS Fifty-four patients (mean +/- S.D. age, 48.4 +/- 12.9 years; TBW, 142.3 +/- 41.7 kg; BMI, 50.5 +/- 12.6 kg/m(2)) completed the study. All three equations were biased in their estimation of CL(cr). Use of MDRD4 and IBW in the Cockcroft-Gault equation underestimated CL(cr), while the Salazar-Corcoran equation and use of TBW or ABW in the Cockcroft-Gault equation overestimated this value. Substitution of fat-free weight or LBW in the Cockcroft-Gault equation provided unbiased estimates of CL(cr). CONCLUSION An LBW estimate, based on TBW and BMI, incorporated into the Cockcroft-Gault equation provided an unbiased, relatively precise, accurate, and clinically practical estimate of 24-hour measured CL(cr) in morbidly obese patients.

Comparison of Oxidative Stress Markers After Intravenous Administration of Iron Dextran, Sodium Ferric Gluconate, and Iron Sucrose in Patients Undergoing Hemodialysis

Study Objective. To compare non–transferrin‐bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose.

Reduced Drug Use and Hospitalization Rates in Patients Undergoing Hemodialysis Who Received Pharmaceutical Care: A 2‐Year, Randomized, Controlled Study

Study Objective. To investigate the impact of a pharmaceutical care program managed by clinical pharmacists on drug use, drug costs, hospitalization rates, and drug‐related problems (DRPs) in ambulatory patients undergoing hemodialysis.

Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival

BackgroundInfections in hemodialysis (HD) patients lead to high morbidity and mortality rates and are associated with early cardiovascular mortality, possibly related to chronic inflammation. Intravenous (IV) iron is widely administered to HD patients and has been associated with increased oxidative stress and dysfunctional cellular immunity. The purpose of this study was to examine the effect of three commercially available IV iron preparations on intracellular reactive oxygen species generation and lymphocyte subpopulation survival.MethodsPeripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 μg/mL of sodium ferric gluconate (SFG), iron sucrose (IS) or iron dextran (ID) for 24 hours. Cells were then probed for reactive oxygen species (ROS) with dichlorofluorescein-diacetate. In separate studies, isolated PBMCs were incubated with the 25, 50 or 100 μg/mL iron concentrations for 72 hours and then stained with fluorescein conjugated monoclonal antibodies for lymphocyte subpopulation identification. Untreated PBMCs at 24 hours and 72 hours served as controls for each experiment.ResultsAll three IV iron preparations induced time dependent increases in intracellular ROS with SFG and IS having a greater maximal effect than ID. The CD4+ lymphocytes were most affected by IV iron exposure, with statistically significant reduction in survival after incubation with all three doses (10, 25 and 100 μg/mL) of SFG, IS and ID.ConclusionThese data indicate IV iron products induce differential deleterious effects on CD4+ and CD16+ human lymphocytes cell populations that may be mediated by intracellular reactive oxygen species generation. Further studies are warranted to determine the potential clinical relevance of these findings.

Medication Reconciliation and Therapy Management in Dialysis-Dependent Patients: Need for a Systematic Approach

Patients with ESRD undergoing dialysis have highly complex medication regimens and disproportionately higher total cost of care compared with the general Medicare population. As shown by several studies, dialysis-dependent patients are at especially high risk for medication-related problems. Providing medication reconciliation and therapy management services is critically important to avoid costs associated with medication-related problems, such as adverse drug events and hospitalizations in the ESRD population. The Medicare Modernization Act of 2003 included an unfunded mandate stipulating that medication therapy management be offered to high-risk patients enrolled in Medicare Part D. Medication management services are distinct from the dispensing of medications and involve a complete medication review for all disease states. The dialysis facility is a logical coordination center for medication management services, like medication therapy management, and it is likely the first health care facility that a patient will present to after a care transition. A dedicated and adequately trained clinician, such as a pharmacist, is needed to provide consistent, high-quality medication management services. Medication reconciliation and medication management services that could consistently and systematically identify and resolve medication-related problems would be likely to improve ESRD patient outcomes and reduce total cost of care. Herein, this work provides a review of available evidence and recommendations for optimal delivery of medication management services to ESRD patients in a dialysis facility-centered model.

Medication-related Problems in CKD

Patients with CKD are often prescribed heterogeneous medications to treat disease-associated comorbidities, to slow down progression of the disease, and to minimize morbidity and mortality rates. However, the medication regimens of this population are very complex, leading to an increased potential for medication-related problems (MRPs). As kidney function declines, the type and amount of medications a patient consumes increases, thereby putting them at a higher risk for MRPs. MRPs have been known to be associated with morbidity, mortality, and a lower quality of life. This review will summarize data on the prevalence and effect of MRPs, and strategies that can be used by clinicians to reduce and resolve MRPs.

Non-Transferrin-Bound Iron Is Associated with Enhanced Staphylococcus aureus Growth in Hemodialysis Patients Receiving Intravenous Iron Sucrose

Background: Hemodialysis vascular access infections are most frequently caused by Staphylococcus spp. The purpose of this study was to determine if S. aureus growth is enhanced after administration of IV iron sucrose and to establish a relationship between the appearance of non-transferrin-bound iron (NTBI) and S. aureus growth. Methods: Serum samples were obtained from 12 hemodialysis patients receiving maintenance doses of 100 mg of iron sucrose at baseline and 5, 30, 90, 220 min and 48 h after iron administration. Assays for NTBI and transferrin saturation were performed. S. aureus isolates were used to inoculate patient serum samples. Bacterial growth was determined by optical density. Results: Six of 12 patients had NTBI present within 30 min of the iron dose. NTBI was present more frequently in patients with baseline transferrin saturation values >30% (p < 0.05). Bacterial growth was significantly greater in patients who had NTBI present at 5, 90 and 220 min after iron administration compared to those who did not have NTBI present. Conclusions: Doses of 100 mg of iron sucrose are associated with the presence of NTBI and enhanced S. aureus growth.

Health-related quality of life is maintained in hemodialysis patients receiving pharmaceutical care: A 2-year randomized, controlled study

End‐stage renal disease and initiation of hemodialysis (HD) adversely affect health‐related quality of life (HRQOL). There are currently no data evaluating the effect of pharmaceutical care (PC) on HRQOL in HD patients. HD patients were randomized to receive PC; one‐on‐one, in‐depth medication reviews conducted by a clinical pharmacist or Standard of Care (SOC); and brief medication reviews conducted by dialysis nurses. The renal quality of life profile (RQLP) was administered at baseline and then at 1 and 2 years after study initiation. The RQLP is a 43‐item questionnaire that has 5 dimensions: Eating/Drinking, Physical Activities, Leisure Time, Psychosocial Activities, and Impact of Treatment, where increasing scores reflect worsening of HRQOL. A total of 107 patients were enrolled (SOC: n=46; PC: n=61). Besides gender, there were no differences in the demographics or the baseline total RQLP scores. The mean±SD total RQLP scores at Year 1 were significantly worse in SOC compared with PC (88±31 vs. 71±34, respectively; P=0.03). Significant worsening of Eating and Drinking (5.9±3.3 vs. 4.4±3.1, respectively; P=0.04), Physical Activities (37±13.6 vs. 30±16.3, respectively; P=0.04), and Leisure Time scores (8.3±3.4 vs. 5.9±3.6, respectively; P=0.03) was also observed in the SOC group. After 2 years, only the SOC patients had worsening of Leisure Time (7.5±3.0 vs. 5.2±3.9, respectively; P=0.04). No other parameters were different between the groups after 2 years. These data indicate that patients who have clinical care provided by pharmacists do not have worsened HRQOL after 1 year and are able to maintain HRQOL for an additional year.

Ferumoxytol: a silver lining in the treatment of anemia of chronic kidney disease or another dark cloud?

Intravenous iron therapy is pivotal in the treatment of anemia of chronic kidney disease to optimize the response of hemoglobin to erythropoiesis-stimulating agents. Intravenous iron use in patients with chronic kidney disease is on the rise. Recent clinical trial data prompting safety concerns regarding the use of erythropoiesis-stimulating agents has stimulated new US Food and Drug Administration label changes and restrictions for these agents, and has encouraged more aggressive use of intravenous iron. The currently available intravenous iron products differ with regard to the stability of the iron-carbohydrate complex and potential to induce hypersensitivity reactions. Ferumoxytol is a newer large molecular weight intravenous iron formulation that is a colloidal iron oxide nanoparticle suspension coated with polyglucose sorbitol carboxymethyl ether. Ferumoxytol has robust iron-carbohydrate complex stability with minimal dissociation or appearance of free iron in the serum, allowing the drug to be given in relatively large doses with a rapid rate of administration. Clinical trials have demonstrated the superior efficacy of ferumoxytol versus oral iron with minimal adverse effects. However, recent postmarketing data have demonstrated a risk of hypersensitivity that has prompted new changes to the product information mandated by the Food and Drug Administration. Additionally, the long-term safety of this agent has not been evaluated, and its place in the treatment of anemia of chronic kidney disease has not been fully elucidated.

Plasma Pharmacokinetics of Two Consecutive Doses of Ferumoxytol in Healthy Subjects

Intravenous (IV) iron is used to treat iron‐deficiency anemia in patients with chronic kidney disease (CKD). Ferumoxytol is a novel iron formulation administered rapidly as two IV boluses of 510 mg each. In this placebo‐controlled, double‐blind, parallel‐group study, 58 healthy volunteers received ferumoxytol in two 510 mg doses administered 24 h apart. Population pharmacokinetics (PK) analysis was conducted, and a two‐compartment open model with zero‐order input and Michaelis–Menten elimination was found to best describe the data. The population mean estimates for volume of distribution of the central compartment (V1), maximal elimination rate (Vmax), and ferumoxytol concentration at which rate of metabolism would be one‐half of Vmax (Km) were 2.71 l, 14.3 mg/h, and 77.5 mg/l, respectively. When the effect of body weight on V1 was added in the analysis, interindividual variability was found to be reduced. A noncompartmental analysis of two simulated 510‐mg ferumoxytol doses was also performed to provide clinically interpretable data on half life and exposure. Ferumoxytol given as two consecutive 510‐mg doses was well tolerated.