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ONCOLOGY

Novel Algorithm for More Accurate Calculation of Renal Function in Adults with Cancer

PhD Candidate, Pharmacist, Department of Hospital Pharmacy, University of Tuebingen, Tuebingen, Germany

Hans-Peter Lipp, PhD

Director of Department of Hospital Pharmacy, University of Tuebingen

Klaus Dietz, PhD

Professor of Medical Biometry, University of Tuebingen

Joerg Thomas Hartmann, MD

Professor of Internal Medicine-Oncology-Hematology, South West German Cancer Center, University of Tuebingen

Carsten Bokemeyer, MD

Professor of Internal Medicine-Oncology-Hematology, University Medical Center Eppendorf, Hamburg, Germany

Reprints: Mrs. Holweger, Department of Hospital Pharmacy, Roentgenweg 9, 72076 Tuebingen, Germany, fax 49 7071-29-5050, karin.holweger{at}med.uni-tuebingen.de

BACKGROUND: Cytotoxic agents have a narrow therapeutic window. A high percentage of some of them is renally excreted in unchanged form. Accurate assessment of an individual's glomerular filtration rate (GFR) helps to predict the pharmacokinetic behavior of those drugs more precisely. GFR calculations, however, have their limitations.

OBJECTIVE: To establish a more accurate calculation of renal function over a broad range of constitutive GFR values.

METHODS: Patients with cancer were included in the analysis. Serum levels of cystatin C, creatinine, urea, albumin, and β-trace protein were measured, and GFR was calculated by 8 mathematical formulas. The results were compared with creatinine clearance (CrCl) calculated from timed urine specimens.

RESULTS: One hundred two patients were evaluated: median age, 57.5 years (range 20-91); females, 52; males, 50; and mean urinary CrCl, 77.0 mL/min. The bias (mean percentage error) was -2% and the precision (mean absolute percentage error) was 23% for the Modification of Diet in Renal Disease (MDRD) estimation of GFR. All equations significantly overestimated CrCl in patients with measured clearance less than 50 mL/min (p < 0.05), with the exception of the modified Salazar-Corcoran formula. All equations underestimated CrCl in patients with measured clearance greater than 100 mL/min. The Wright formula was the least biased and most precise (-5%, 16%, respectively). In patients with measured CrCl 50-100 mL/min, the MDRD calculation had a bias of -4% and a precision of 17%. The Jelliffe and Larsson equations were associated with significant sex bias (p < 0.05).

CONCLUSIONS: These observations suggest that individual GFR values over a broad range cannot be calculated accurately enough with only one selected formula. It may be useful to classify renal function of patients with cancer according to the novel algorithm by using MDRD first and then to subsequently calculate GFR in higher and lower ranges with the Wright and modified Salazar-Corcoran formulas, respectively. This algorithm should be validated using larger numbers of patients.

Key Words: algorithm, β-trace protein, cancer, Cockcroft-Gault, creatinine clearance, cystatin C, glomerular filtration rate

Published Online, November 25, 2008. www.theannals.com, DOI 10.1345/aph.1L216