Tubular secretion of creatinine and kidney function: an observational study

Abstract

Background: Prior 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.

Methods: To 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.

Results: Observed 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.

Conclusions: These 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.

Keywords: Chronic kidney disease (CKD); Creatinine clearance (CrCl); Glomerular filtration rate (GFR); Measurement error; Tubular secretion of creatinine.

Fig. 1

Distribution of iGFR, CrCl, as well as CrCl/iGFR ratio stratified by categories of iGFR (a) and by categories of CrCl (b) in 802 AASK, 797 MDRD and 1693 Mayo CKD participants (box plots show median, interquartile range and outliers; whiskers represent the highest and lowest values that are not outliers more than 1.5 box lengths from one hinge of the box). The data in the figure represents the corresponding median CrCl/iGFR ratios

Fig. 2

Change in mean (±standard deviation [SD]) iGFR and mean (±SD) CrCl/iGFR ratio longitudinally among MDRD study participants divided into those with decreasing iGFR (n = 508) or increasing iGFR (n = 172)

Fig. 3

Change in mean (±SD) CrCl and mean (±SD) CrCl/iGFR ratio longitudinally among MDRD study participants divided into those with decreasing CrCl (n = 489) or increasing CrCl (n = 191)