Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C

Abstract

BACKGROUND Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR. METHODS Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 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 per minute per 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 per minute per 1.73 m2 with the combined equation, as compared with 3.7 and 3.4 ml per minute per 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 (inter-quartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 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 to 74 ml per minute per 1.73 m2, the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m2 or greater than or equal to 60 ml per minute per 1.73 m2 (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 as having a GFR of 60 ml or higher per minute per 1.73 m2. CONCLUSIONS 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. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)

Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

“…Thus, risk of CVD could be more evident when reduced kidney function and anemia concomitantly exist. In the present study, we noted that the association of low eGFR with CVD risk was slightly stronger in participants with anemia, which was generally consistent with previous studies investigating CHD17 and stroke18 outcomes.…”

Correlation of Microalbuminuria with Estimated GFR (eGFR) by Cockcroft–Gault and MDRD Formula in Type 2 Diabetics and Hypertensives

“…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 CKD. The cystatin equation is not more accurate than creatinine equation, but the combined creatinine-cystatin equation is more precise than either of the two methods used separately [11]. Serum creatinine alone should not be used to assess the GFR or to detect the presence of CKD because it is affected by the GFR and by factors independent of GFR, including age, sex, race, body size, diet, certain drugs, and laboratory analytical methods [12].…”

Self‐Reported Smoking, Urine Cotinine, and Risk of Cardiovascular Disease: Findings From the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) Prospective Cohort Study

“…Plasma glucose was measured by dry chemistry (Eastman Kodak, Rochester, NY). Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) combined creatinine–cystatin C equation 25. Hypertension was defined as systolic blood pressure of ≥140 mm Hg, a diastolic blood pressure of ≥90 mm Hg, and/or the use of antihypertensive medication, in accordance with recommendations from the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 26…”