Joanna Q. Hudson

Comparative evaluation of the Cockcroft-Gault Equation and the Modification of Diet in Renal Disease (MDRD) study equation for drug dosing: an opinion of the Nephrology Practice and Research Network of the American College of Clinical Pharmacy.

Accurate assessment of kidney function is an important component of determining appropriate drug dosing regimens. Nearly all manufacturer‐recommended dosage adjustments are based on creatinine clearance ranges derived from clinical pharmacokinetic studies performed during the drug development process. The Cockcroft‐Gault (CG) equation provides an estimate of creatinine clearance and is the equation most commonly used to determine drug dosages in patients with impaired kidney function. The Modification of Diet in Renal Disease (MDRD) study equation has also been proposed for this purpose. Published studies report that drug dosages determined by the two equations do not agree in 1 0–40% of cases. However, interpretation and comparison of these studies are complicated by the variable creatinine methods used for calculating CG and MDRD estimates, the patient populations studied, and a lack of outcomes data demonstrating the clinical significance of dosing discrepancies. Moreover, the impact of reporting standardized serum creatinine values on the accuracy of the CG equation and corresponding drug dosing regimens have been questioned. Currently, no prospective pharmacokinetic studies have been conducted with use of the MDRD equation to generate dosing recommendations, and limited data are available to support its use in some patient populations representing demographic extremes. Collectively, these issues have resulted in considerable confusion among clinicians and have fueled a healthy debate on whether or not to use the MDRD equation to determine drug dosages. Each of these issues is reviewed, and a proposed algorithm for using creatinine‐based kidney function assessments in drug dosing is provided. Knowledge of the advantages, limitations, and clinical role of each equation will facilitate their safe and effective use in drug dosing.

Vancomycin‐resistant Enterococcus bacteremia: An evaluation of treatment with linezolid or daptomycin

BACKGROUND Due to high rates of resistance and a limited number of efficacious antimicrobials for vancomycin-resistant Enterococcus (VRE), appropriate antibiotic selection is vital to treatment success. The purpose of this study was to assess clinical and microbiologic outcomes associated with the use of linezolid or daptomycin in the treatment of VRE bacteremia. METHODS A retrospective analysis of adult patients with VRE bacteremia between January 2004 and July 2009 was conducted at a tertiary care hospital in the United States. Clinical and microbiologic outcomes for both therapies were evaluated using multiple criteria. RESULTS Of the 361 patients with VRE bacteremia identified, 201 were included in the study (linezolid group, n = 138; daptomycin group, n = 63). More patients in the daptomycin group had hematologic malignancies (33% vs 14%) or received liver transplants (13% vs 4%). There was no difference in clinical or microbiologic cure between the linezolid and daptomycin groups (74% vs 75% and 94% vs 94%, respectively). Recurrence was documented in 3% of linezolid patients vs 12% of daptomycin patients (P = 0.0321). Reinfection was noted in 1% of patients in the linezolid group vs 6% of patients in the daptomycin group (P not significant). The average length of stay (LOS) was 37 days for the linezolid group vs 40 days for the daptomycin group (P not significant). Overall mortality was 20%, occurring in 25/138 linezolid patients vs 15/63 daptomycin patients (P not significant). CONCLUSIONS No differences in clinical or microbiologic cure rates, LOS, or mortality were identified between the groups. Various factors may have contributed to the significantly higher recurrence of VRE bacteremia in daptomycin patients. This study suggests that linezolid and daptomycin appear equally efficacious in the treatment of VRE bacteremia.

Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient

Purpose of reviewAssessment of kidney function is necessary to stage chronic kidney disease (CKD) and appropriately dose medications. The Cockcroft–Gault equation provides an estimate of creatinine clearance (eClCr) and is the method commonly referenced in pharmacokinetic studies. The Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology Collaboration (EPI) equations provide an estimate of glomerular filtration rate (eGFR), with the MDRD eGFR now automatically reported by most clinical laboratories. This review describes the differences in the Cockcroft–Gault, MDRD, and CKD-EPI equations and considerations when applying estimates from these equations for drug dosing. Recent findingsStudies evaluating drug-dosing regimens using eClCr and eGFR differ in their results depending on the population in which the equation is applied, the adjustment factors used to account for body size, and the number of dosing levels for a particular medication. The largest study to evaluate drug regimen design by method concluded that either the eGFR or Cockcroft–Gault estimates could be used for drug dosing. Differences in methodology among studies are a key factor in evaluating these results and will be highlighted in this review. SummaryThe Cockcroft–Gault, MDRD, and CKD-EPI equations provide reasonable estimates of kidney function; however, clinicians must understand the limitations when using these estimates for drug regimen design.

Considerations for optimal iron use for anemia due to chronic kidney disease

BACKGROUND Availability of recombinant human erythropoietin (rHuEPO) has improved the treatment of anemia due to chronic kidney disease (CKD). Iron deficiency is the most common cause of resistance to rHuEPO therapy, contributing to ineffective erythropoiesis and hematocrit/hemoglobin values below the recommended target range (33%-36%/11-12 g/dL). I.v. iron supplementation is necessary to meet increased iron demands from stimulation of erythropoiesis and chronic blood loss; however, questions remain as to the optimal supplementation strategy to maintain appropriate yet safe iron status. Treatment guidelines for anemia management have been developed through the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). OBJECTIVE This review presents the basis of need for the NKF-K/DOQI guidelines and includes detailed information concerning iron physiology, metabolism, iron preparations, and evaluation of iron status. METHODS This review was based on a MEDLINE search and complemented by references from the NKF-K/DOQI guidelines (whose review extended beyond MEDLINE). References focusing on normal iron physiology and metabolism, alterations in iron physiology in patients with CKD, laboratory evaluation methods, and strategies for iron supplementation were obtained from MEDLINE and reviewed for content. RESULTS Controversy over appropriate use of iron supplementation has led to disparity in accepted practice procedures. Oral iron (ferrous salts and polysaccharide iron complex) and i.v. iron preparations (iron dextran, sodium ferric gluconate, and iron sucrose) are available. Problems with oral iron supplementation include limited absorption and patient noncompliance. Although most available data on i.v. iron use in the United States are specific to iron dextran preparations, published information based on clinical use of sodium ferric gluconate and iron sucrose products has been promising. The use of chronic i.v. iron administration to sustain iron stores has been more widely accepted to prevent development of absolute and functional iron deficiency. CONCLUSIONS Although iron therapy is commonly warranted in patients with CKD, questions remain as to the most favorable supplementation strategy to optimize therapy through improvements in hematocrits, efficient use of rHuEPO, and maintenance of appropriate and safe iron levels. Clinicians will need to devise strategies based on the compilation of information from clinical experience and the available literature. Clinical practice guidelines devised by the NKF-K/DOQI have provided a useful tool for the medical community using both these resources.

Caring for Patients with Chronic Kidney Disease: A Joint Opinion of the Ambulatory Care and the Nephrology Practice and Research Networks of the American College of Clinical Pharmacy

An increasing number of patients are developing chronic kidney disease (CKD). Appropriate care for patients with CKD must occur in the earliest stages, preferably before CKD progresses to more severe stages. Therefore, recognition and treatment of CKD and its associated complications must occur in primary care settings. Patients with CKD often have comorbid conditions such as diabetes mellitus, hypertension, and dyslipidemia, creating specific considerations when treating these diseases. Also, these patients have CKD‐related conditions, including anemia and renal osteodystrophy, that are not traditionally evaluated and monitored by the primary care practitioner. Collectively, many opportunities exist for pharmacists who practice in the primary care setting to improve the care of patients with CKD.

Secondary Hyperparathyroidism in Chronic Kidney Disease: Focus on Clinical Consequences and Vitamin D Therapies

Objective: To assess vitamin D–based treatment approaches for secondary hyperparathyroidism and its complications. Data Sources: A literature search was performed using MEDLINE (1990–February 28, 2006). Key words used were chronic kidney disease and vitamin D to identify relevant papers published in English. Study Selection and Data Extraction: From the database of articles generated, 48 papers were identified. Titles and abstracts were examined to identify those directly related to the objective. Discussion was expanded through the bibliographies of cited articles. Data Synthesis: The increasing prevalence of chronic kidney disease (CKD) in the US indicates an urgent need for treatment strategies to delay or prevent disease progression. Abnormalities in phosphorus and calcium homeostasis, vitamin D levels, and the subsequent development of secondary hyperparathyroidism (SHPT) are secondary complications of CKD associated with increased morbidity and mortality. Management options include dietary phosphorus restriction, phosphate binders and/or calcium supplementation, vitamin D supplementation, and calcimimetics. Vitamin D supplementation has received increased attention given the prevalence of vitamin D deficiency in patients with CKD and the beneficial effect of correcting this deficiency. Conclusions: Early identification and intervention appropriate to the stage of CKD are likely to improve patient outcomes. Improved knowledge of interactions between vitamin D and vitamin D receptors has led to the development of vitamin D analogs and calcimimetics, which offer benefits in the management of SHPT. Integrating available treatment options into practice to achieve optimal therapeutic goals of SHPT based on the stage of CKD is a significant challenge for pharmacists managing patients with CKD.

Epistaxis associated with dabigatran in an elderly patient with reduced creatinine clearance.

Since its approval in October 2010, dabigatran etexilate use has increased due to ease of monitoring and simplified dosing compared with warfarin.[1][1] The RE-LY trial led to FDA approval of dabigatran etexilate at a dosage of 150 mg twice daily.[2][2]–[4][3] Dabigatran etexilate 150 mg twice

Darbepoetin alfa, a new therapy for the management of anemia of chronic kidney disease.

Anemia of chronic kidney disease (CKD) results primarily from a deficiency of the hormone erythropoietin. Treatment of anemia in the early stages of CKD is essential to reduce the risk of developing anemia‐associated complications and to improve health‐related quality of life. Treatment with recombinant human erythropoietin (r‐HuEPO, epoetin alfa) can correct erythropoietin deficiency and increase red blood cell production, but the short half‐life of r‐HuEPO necessitates frequent injections. Reducing the frequency of administration has potential benefits for both patients and health care providers. Darbepoetin alfa is a new erythropoietic protein with greater biologic activity and a longer dosing interval than those of r‐HuEPO. It has been shown to be effective when administered once/week and once every 2, 3, or 4 weeks, and is well tolerated. With the ability to simplify anemia management by allowing less frequent dosing, darbepoetin alfa offers an effective alternative to r‐HuEPO for the treatment of anemia of CKD.

Evaluation of warfarin dose requirements in patients with chronic kidney disease and end-stage renal disease.

The effect of chronic kidney disease (CKD) on warfarin has gained attention because of an increased risk of thromboembolism and an increased risk of bleeding associated with warfarin treatment in these patients. Data suggest that patients with reduced kidney function require lower warfarin doses; however, relatively few patients with end‐stage renal disease (ESRD) were included in previous studies. The goal of this study was to evaluate warfarin dosing requirements and time to reach therapeutic international normalized ratio (INR) in patients with CKD stages 3–5 and ESRD compared with patients with normal kidney function (NKF).

Evaluation of antibiotic prescribing patterns in patients receiving sustained low-efficiency dialysis: opportunities for pharmacists

Sustained low‐efficiency dialysis (SLED) is a ‘hybrid’ form of continuous renal replacement therapy; however, there is very limited information on drug disposition during this procedure. Individuals requiring SLED are often critically ill and require antibiotics. The study aim was to evaluate antibiotic orders for patients requiring SLED compared to literature‐based recommendations. We also evaluated whether doses were administered as prescribed and assessed clinical and microbiologic cure.