Estimated glomerular filtration rate leads to higher drug dose recommendations in the elderly compared with creatinine clearance.

PURPOSE: The elderly are at risk for adverse drug events because of inappropriate dosing of renally eliminated medications. The purpose of this study was to evaluate differences in estimates of kidney function and recommended doses of select medications in the elderly using the Modification of Diet in Renal Disease (MDRD) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with the Cockcroft-Gault (CG) equation. METHODS: Patients 65 years of age and older were included in this retrospective, observational analysis. Kidney function was estimated by CG, MDRD and CKD-EPI equations for all patients and by age category (65-69, 70-79, 80-89 and 90-100 years). Differences in estimates and dosing of allopurinol, enoxaparin, gabapentin, piperacillin/tazobactam and sulfamethoxazole/trimethoprim using the MDRD and CKD-EPI compared with the CG were assessed. RESULTS: In the 4160 patients (98% male, mean age 74 ± 7 years), the MDRD and CKD-EPI estimates were significantly higher than CG estimates for all patients and by age category (p < 0.001). Dosing discordance was predominantly because of a higher dose recommended by MDRD and CKD-EPI estimates compared with CG. Discordance was highest with gabapentin (27%), the medication with the greatest number of dosing stratifications by estimated kidney function, and increased by 66% from the youngest to the oldest age category. CONCLUSIONS: Until newer equations are used uniformly to develop dosing nomograms, it is prudent to adopt a process for drug dosing in the elderly that is more conservative than eGFR based dosing, but that considers the potential for underestimating kidney function with the CG equation.

Accuracy of urine collection methods compared to measured GFR in adults with liver disease.

BACKGROUND: Assessment of kidney function is necessary to stage kidney disease, dose medications, and to make decisions about organ allocation. Estimating equations that incorporate serum creatinine (SCr) are not consistently reliable. However, assessment of creatinine clearance (CrCl) using 24-hour urine collection methods is also prone to errors. The purpose of this study was to evaluate the accuracy of measured CrCl determined using shorter urine collection times compared to glomerular filtration rate measured by (125)I-iothalamate clearance ((125)I-CL) in patients with liver disease. METHODS: Adult patients with chronic liver disease were enrolled. All patients received (125)I-iothalamate and had a catheter placed for urine collection. Blood samples were collected at designated times over 8 hours to determine (125)I-CL. CrCl was determined from a 1-hour and a 4-hour urine collection and compared to (125)I-CL. RESULTS: Characteristics of the eight patients enrolled included age 52 ± 6 years; SCr 1.2 ± 0.4 mg/dL; and Model for End-stage Liver Disease score of 13 ± 3. All patients were Child-Pugh Class B. Mean estimates of kidney function (mean ± SD, mL/min/1.73 m(2)) by method were 74 ± 38 for (125)I-CL, 79 ± 28 for the 1-hour urine collection, and 72 ± 26 for the 4-hour urine collection. Measured CrCl did not differ significantly from (125)I-CL (P = .641 for 1-hour CrCl versus (125)I-CL, and P = 1.0 for the 4-hour CrCl versus (125)I-CL). CONCLUSION: When urine collection methods are necessary for an individualized assessment of kidney function, shorter collection times can provide accurate results and would be more feasible for the patient.

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.

Perceptions of pharmacists about adverse effects of corticosteroid therapy: focus on osteoporosis.

OBJECTIVE: To assess the perceptions of pharmacists regarding the adverse effects of corticosteroids, in particular corticosteroid-induced osteoporosis. DESIGN: Mailed survey of a random sample of pharmacists. SETTING: Richmond, Virginia. PARTICIPANTS: 350 community and hospital pharmacists. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Respondents' knowledge of adverse effects of corticosteroid therapy in men, premenopausal women, and postmenopausal women; the content of respondents' usual patient counseling for low- and high-dose therapy; and respondents' opinions of regimens for prevention of osteoporosis. RESULTS: Pharmacists associated gastritis, weight gain, and mood changes with corticosteroid use in a hypothetical 45-year-old man or 45-year-old premenopausal woman. For a hypothetical 65-year-old postmenopausal woman, pharmacists more frequently counseled about weight gain, osteoporosis, and gastritis. Patient counseling focused on these adverse effects for both low-dose (5 to 10 mg/day) and high-dose (> or = 30 mg/day) prednisone use. Osteoporosis was considered more likely in patients receiving high-dose corticosteroids on a long-term basis. CONCLUSION: Pharmacists responding to this survey frequently overlooked the association between low- and high-dose corticosteroid use and decreased bone density. Educational efforts are needed so that pharmacists can fulfill their potential for educating patients, monitoring corticosteroid therapy, and detecting drug-induced complications.