In a recent issue of the British Medical Journal, Raynaud et al. (1) reported on the development and validation of a creatinine-based estimated glomerular filtration rate (eGFRcr) equation for use in kidney transplant recipients. There is good reason to think that eGFRcr equations developed for use in the general population, such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, would have large errors in some kidney transplant patients. Following transplantation, kidney transplant recipients may have low muscle mass, reduced activity, or decreased protein intake or use medications that affect muscle mass (such as glucocorticosteroids) or that inhibit renal tubular secretion of creatinine (such as trimethoprim), all of which can lead to changes in serum creatinine independent of GFR (2, 3). GFR is used for many critical clinical decisions in kidney transplant recipients, such as detection of rejection and consideration of biopsy, or decisions regarding selection and dosage of prophylactic antimicrobials or use of contrast imaging to detect transplant complications (4, 5). As such, a comprehensive approach for assessment of GFR for patients with kidney transplants is necessary and has been missing.
The authors’ equation was developed in 3622 patients from 3 French transplant centers and validated in 11,867 patients—from 8 centers in Europe, 1 center in Australia, 1 clinical center and 1 trial in the United States, and 1 international trial—who received kidney transplants between 2000 and 2021. Across the 12 validation cohorts, accuracy of the newly developed equation was variable, with percentage of estimates within 30% of measured GFR (mGFR; P30) that ranged from 73% to 91%. (1 - P30 is a measure of large errors.) It is generally established that P30 >75% is acceptable for many clinical decisions and that P30 >90% is optimal. The variation may have been due to a differing prevalence of clinical factors mentioned above but may also have been due to methodological differences in measurement of GFR or in creatinine. In particular, the creatinine assays were variably standardized within, as well as across, cohorts—a requirement for a validated equation (6, 7). Among these cohorts, the differential accuracy compared with CKD-EPI equations was also variable, with the difference in P30 between the two equations ranging from 0.1% to 16% (median difference of 3.8%). The variation in the relative accuracy between the equations likely reflects methodological differences in measurement of GFR or in creatinine, as well as differences in population characteristics, rather than having a kidney transplant. Indeed, the similar performance across the equations confirms prior studies demonstrating that the CKD-EPI equations are as accurate in kidney transplant recipients as in patients with other causes of CKD and who do not have a transplant (8, 9).
Thus, in our view, these results do not change the current recommendations for a single equation to report GFR by clinical laboratories for all adults or in using that eGFR value for routine care for most kidney transplant patients. However, the question of a comprehensive approach for assessment of GFR remains open. eGFRcr is recommended as the initial test, followed by eGFR from the combination of creatinine and cystatin C (eGFRcr-cys) or mGFR as supportive tests, depending on the clinical setting (2, 7) (Figure 1). Cystatin C has not been evaluated sufficiently in kidney transplant recipients, and careful investigations are required given the possible effect of medications on level of cystatin C independent of mGFR (10, 11).
This article reminds us of the challenge of assessment of GFR in transplant patients, and we encourage continued rigorous investigation. We recommend further studies to evaluate the accuracy of eGFRcr and eGFRcr-cys equations in kidney transplant recipients with specific consideration of the clinical settings, such as medication use and health status, which can inform a holistic approach to GFR assessment.
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Keddis MT, et al. Creatinine-based and cystatin C-based GFR estimating equations and their non-GFR determinants in kidney transplant recipients. Clin J Am Soc Nephrol 2016; 11:1640–1649. doi: 10.2215/CJN.11741115
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