Abstract and Introduction
Abstract
Surveillance of glomerular filtration rate (GFR) is crucial in the management of kidney transplant recipients. With especial emphasis on serum creatinine (SCr) calibration assay, we assessed the performance of estimation equations as compared to iothalamate GFR (iGFR) in 209 patients using the modification of diet in renal disease (MDRD), Nankivell and Cockcroft-Gault methods. Fifty-five percent of patients were treated with a calcineurin inhibitor (CNI) and all were taken trimethroprim-sulfametoxazole at the time of SCr measurement. The mean iGFR was 44 ± 26 mL/min/1.73 m. The MDRD equation showed a median difference of 0.9 mL/min/1.73 m with 53% of estimated GFR within 20% of iGFR. Median differences were 7.5 and 7.0 mL/min/1.73 m for Nankivell and Cockcroft-Gault formulas, respectively. The accuracy of the Nankivell and Cockcroft-Gault formulas was such that only 38% and 37% of estimations, respectively, fell within 20% of iGFR. The performance of all equations was not uniform throughout the whole range of GFR, with some deterioration at the extremes of GFR levels. In addition, good performance of the MDRD equation was seen in subjects taking CNI. In conclusion, the overall performance of the MDRD equation was superior to the Nankivell and Cockcroft-Gault formulas in renal transplant recipients including subjects treated with CNI.
Introduction
Management of kidney transplant recipients requires a simple, reliable and accurate method for the estimation of glomerular filtration rate (GFR). Using solely serum creatinine (SCr) to estimate GFR is the simplest and most commonly used approach; although when compared to creatinine clearances and isotope measurements of GFR, its performance is quite variable particularly in renal transplant patients. Creatinine clearance is also an inaccurate estimate of GFR especially at the extremes of age and GFR. In contrast, the clearance of some radioisotopes like I-iothalamate (iGFR) demonstrated accurate measurement of GFR in a non-transplant population when compared to the 'gold standard' inulin clearance. However, the expense and complexity of this tool limit its wide application.
In order to accurately and simply estimate GFR, different creatinine-based estimation equations have been developed mainly in the non-transplant population. The most widely used methods are Cockcroft-Gault (CG), 4-variable modification of diet in renal disease (MDRD) and, in kidney transplant recipients, the Nankivell formula. Special emphasis needs to be placed on SCr calibration bias because it is a determining factor in these equations. It has been clearly demonstrated that the assessment of the performance of these equations without careful SCr calibration could greatly impair the clinician's ability to interpret the results. A few European studies tested the applicability of these formulas to a kidney transplant population; however, these analyses were done in the absence of rigorous assessment of SCr measurement calibration bias.
The purpose of this study was to evaluate the performance of the four-variable MDRD, Nankivell and Cockcroft-Gault equations as compared to measurements of GFR by I-iothalamate renal clearance in a US cohort of renal transplant recipients that includes African-American subjects with stable graft function and to provide insight into the mechanisms involved in GFR estimation. Special emphasis was placed on calibration of the SCr assay. We showed that the MDRD equation overall performs better with respect to bias and accuracy than the Nankivell and Cockcroft-Gault formulas in this study population. Moreover, the performance of these equations is not affected when applied to individuals treated with a calcineurin inhibitor (CNI).