Estimating the glomerular filtration rate from serum creatinine is better than from cystatin C for evaluating risk factors associated with chronic kidney disease

Abstract

Chronic kidney disease risk factors may associate with the estimated glomerular filtration rate (eGFR) differently than with the measured GFR. To examine this, we evaluated 1150 patients (mean age 65 years) in two community cohorts for risk factors, measured GFR by iothalamate clearance, and eGFR based on creatinine (Cr), cystatin C (CysC), or both. The interaction between each risk factor and eGFR (relative to measured GFR) identified risk factor associations with eGFR along non-GFR pathways. In a subset of 40 patients with two visits, the mean coefficient of variation was 8.2% for measured GFR, 6.4% for eGFRCr, 8.2% for eGFRCr-CysC, and 10.7% for eGFRCysC. The measured GFR was better correlated with eGFRCr-CysC (r, 0.74) than eGFRCr (r, 0.70) or eGFRCysC (r, 0.68). Lower measured GFR associated with lower 24-hour urine creatinine, albuminuria, hypertension, diabetes, higher triglycerides, and higher uric acid. Lower eGFRCr had these same associations except for an association with higher 24-hour urine creatinine along a non-GFR pathway. Lower eGFRCysC and eGFRCr-CysC also had these same associations but also associated with obesity, albuminuria, hypertension, diabetes, higher triglycerides, higher C-reactive protein, and higher uric acid along non-GFR pathways. Thus, cystatin C improves estimation of GFR over creatinine alone; however, the association between most of the risk factors and GFR was more accurate by eGFR based on creatinine alone. This is explained by the association of these risk factors with the non-GFR determinants of cystatin C.

Figure 1

The correlation between measured GFR (mGFR, Y-axis) with A) serum creatinine based estimated GFR with the CKD-EPI equation (eGFR_Cr, X-axis, R=0.70), B) cystatin C based estimated GFR (eGFR_CysC, X-axis, R=0.68), C) serum creatinine and cystatin C based estimated GFR(eGFRC_Cr-CysC, X-axis, R=0.74).

Figure 1

The correlation between measured GFR (mGFR, Y-axis) with A) serum creatinine based estimated GFR with the CKD-EPI equation (eGFR_Cr, X-axis, R=0.70), B) cystatin C based estimated GFR (eGFR_CysC, X-axis, R=0.68), C) serum creatinine and cystatin C based estimated GFR(eGFRC_Cr-CysC, X-axis, R=0.74).

Figure 1

The correlation between measured GFR (mGFR, Y-axis) with A) serum creatinine based estimated GFR with the CKD-EPI equation (eGFR_Cr, X-axis, R=0.70), B) cystatin C based estimated GFR (eGFR_CysC, X-axis, R=0.68), C) serum creatinine and cystatin C based estimated GFR(eGFRC_Cr-CysC, X-axis, R=0.74).

Figure 2

Reliability between duplicate visits of A) measured GFR (mGFR, r =0.76), B) estimated GFR by serum creatinine (eGFR_Cr, r =0.84), C) estimated GFR by cystatin C (eGFR_CysC, r =0.76), and D) estimated GFR by serum creatinine and cystatin C (eGFR_Cr-CysC, r =0.82). The solid circle represents the GENOA subjects who were specifically recruited for 2 duplicate study visits (mean 62 days apart). The open circles represent the subjects who had 2 duplicate study visits because they were participants in both the GENOA and ECAC cohorts (mean 296 days apart).

Figure 2

Reliability between duplicate visits of A) measured GFR (mGFR, r =0.76), B) estimated GFR by serum creatinine (eGFR_Cr, r =0.84), C) estimated GFR by cystatin C (eGFR_CysC, r =0.76), and D) estimated GFR by serum creatinine and cystatin C (eGFR_Cr-CysC, r =0.82). The solid circle represents the GENOA subjects who were specifically recruited for 2 duplicate study visits (mean 62 days apart). The open circles represent the subjects who had 2 duplicate study visits because they were participants in both the GENOA and ECAC cohorts (mean 296 days apart).

Figure 2

Reliability between duplicate visits of A) measured GFR (mGFR, r =0.76), B) estimated GFR by serum creatinine (eGFR_Cr, r =0.84), C) estimated GFR by cystatin C (eGFR_CysC, r =0.76), and D) estimated GFR by serum creatinine and cystatin C (eGFR_Cr-CysC, r =0.82). The solid circle represents the GENOA subjects who were specifically recruited for 2 duplicate study visits (mean 62 days apart). The open circles represent the subjects who had 2 duplicate study visits because they were participants in both the GENOA and ECAC cohorts (mean 296 days apart).

Figure 2

Reliability between duplicate visits of A) measured GFR (mGFR, r =0.76), B) estimated GFR by serum creatinine (eGFR_Cr, r =0.84), C) estimated GFR by cystatin C (eGFR_CysC, r =0.76), and D) estimated GFR by serum creatinine and cystatin C (eGFR_Cr-CysC, r =0.82). The solid circle represents the GENOA subjects who were specifically recruited for 2 duplicate study visits (mean 62 days apart). The open circles represent the subjects who had 2 duplicate study visits because they were participants in both the GENOA and ECAC cohorts (mean 296 days apart).

Figure 3

The association of CKD risk factors with percentage decrease in GFR (↓ GFR) by each method (mGFR, eGFR_Cr, eGFR_Cr-CysC, and eGFR_CysC). The * identifies p<0.05 for eGFR compared to mGFR using model 1 (generalized estimating equations). Risk factor associations with mGFR were more similar to those with eGFR_Cr than with eGFR_Cr-CysC or eGFR_CysC. The one exception was 24-h urine creatinine where eGFR_CysC was more similar to the same association with mGFR.