Estimating Glomerular Filtration Rate From Serum Creatinine and Cystatin C

Study Questions:

What is the validity and performance of equations for estimating glomerular filtration rate (GFR) using either standardized cystatin C alone or using cystatin C combined with standardized creatinine in improving the classification of patients with chronic kidney disease?

Methods:

Using cross-sectional analyses, the investigators developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations, totaling 5,352 participants from 13 studies. These equations were then validated in 1,119 participants from five different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.

Results:

Mean measured GFRs were 68 and 70 ml/min/1.73 m2 of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine–cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml/min/1.73 m2 with the combined equation, as compared with 3.7 and 3.4 ml/min/1.73 m2 with the creatinine equation and the cystatin C equation (p = 0.07 and p = 0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml/min/1.73 m2, respectively [p = 0.001 and p < 0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [p < 0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45-74 ml/min/1.73 m2, the combined equation improved the classification of measured GFR as either <60 ml/min/1.73 m2 or ≥60 ml/min/1.73 m2 (net reclassification index, 19.4% [p < 0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45-59 ml/min/1.73 m2 as having a GFR of ≥60 ml/min/1.73 m2.

Conclusions:

The authors concluded that the combined creatinine–cystatin C equation performed better than equations based on either of these markers alone, and may be useful as a confirmatory test for chronic kidney disease.

Perspective:

This study reports that the combined creatinine–cystatin C equation had greater precision and accuracy, and resulted in more accurate classification of measured GFR. Reporting estimated GFR by means of the combined equation when serum cystatin C is measured may facilitate the clinical interpretation of cystatin C measurements, and estimated GFR based on serum cystatin C may potentially be used as a confirmatory test for chronic kidney disease. Available data suggest that it is also appropriate to use the levels of albuminuria or proteinuria to properly stage chronic kidney disease in addition to improving filtration-marker formulas to estimate GFR. Future studies will need to compare cost-effectiveness and prognostic ability of GFR estimation based on a cystatin C measurement with a urine albumin:creatinine ratio in addition to a creatinine-based GFR estimation.

Keywords: Body Surface Area, Kidney Function Tests, Biological Markers, Cross-Sectional Studies, Glomerular Filtration Rate, Proteinuria, Creatinine, Renal Insufficiency, Chronic, Cystatin C


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