Abstract
BackgroundPrior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts.MethodsTo fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted cross-sectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time.ResultsObserved CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories.ConclusionsThese data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR.
Highlights
Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR)
We recently questioned whether the observed larger ratio of Creatinine clearance (CrCl) to measured GFR among those with lower GFR is due to proportionally greater tubular creatinine secretion with chronic kidney disease (CKD) progression, as is commonly believed, or whether this can be entirely accounted for by measurement error [3, 10]
The CrCl/iothalamate GFR (iGFR) ratio was progressively larger at lower iGFR level when patients were classified by categories of iGFR in both Modification of Diet in Renal Disease study (MDRD) and American Study of Kidney Disease and Hypertension (AASK) (Fig. 1a)
Summary
Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). Our prior study was limited since it was based on only cross-sectional analysis of enrollees from one CKD study (Chronic Renal Insufficiency Cohort [CRIC]), and the CrCl and measured GFR were not obtained simultaneously [3]. The Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK) are ideal data sources since they are both rigorously conducted cohorts and national in scope They have the additional advantage of containing repeated measured of both CrCl and GFR, allowing us to perform longitudinal analyses and add a new dimension not present in our prior paper. We conducted cross-sectional analysis of 4 different Mayo Clinic patient cohorts that underwent clinicallyindicated CrCl and GFR measurements that were performed simultaneously (which should reduce disconcordant measurement error)
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