Combining Cystatin C and Creatinine Yields a Reliable Glomerular Filtration Rate Estimation in Older Adults in Contrast to β-Trace Protein and β2-Microglobulin

Abstract

Background: The glomerular filtration rate (GFR) is the most important measure of kidney function and chronic kidney disease (CKD). This study aims to validate commonly used equations for estimated GFR (eGFR) based on creatinine (cr), cystatin C (cys), β-trace protein (BTP), and β2-microglobulin (B2M) in older adults. Method: We conducted a validation study with 126 participants aged between 72 and 98 with a mean measured GFR (mGFR) by iohexol clearance of 54 mL/min/1.73 m². The eGFR equations (CKD-Epidemiology collaboration [CKD-EPI], Berlin Initiative Study [BIS], Full Age Spectrum [FAS], Modification of Diet in Renal Disease [MDRD]_cr, Caucasian-Asian-Pediatric-Adult [CAPA]_cys, Lund-Malmö Revised [LM-REV]_cr, and MEAN-LM-CAPA_cr-cys), were assessed in terms of bias (median difference: eGFR-mGFR), precision (interquartile range of the differences), and accuracy (P30: percentage of estimates ±30% of mGFR). The equations were compared to a benchmark equation: CKD-EPI_cr-cys. Results: All cystatin C-based equations underestimated the GFR compared to mGFR, whereas bias was mixed for the equations based only on creatinine. Accuracy was the highest for CKD-EPI_cr-cys (98%) and lowest for MDRD (82%). Below mGFR 45 mL/min/1.73 m² only equations incorporating cystatin C reached P30 accuracy >90%. CKD-EPI_cr-cys was not significantly more accurate than the other cystatin C-based equations. In contrast, CKD-EPI_cr-cys was significantly more accurate than all creatinine-based equations except LM-REV_cr. Conclusion: This study confirms that it is reasonable to use equations incorporating cystatin C and creatinine in older patients across a wide spectrum of GFR. However, the results call into question the use of creatinine alone below mGFR 45 mL/min/1.73 m². B2M and BTP do not demonstrate additional value in eGFR determination in older adults.

Kidney function estimates using cystatin C versus creatinine: Impact on medication prescribing in acutely hospitalized elderly patients

“…Differences between creatinine‐ and cystatin C‐based equations are similar to those observed by Jacobs et al in frail elderly psychiatric patients. However, these differences were notably larger in our population compared with similar studies in community‐dwelling older populations . CKD‐EPI Cr is commonly used for medication prescribing in clinical settings, while CG Cr is often used for pharmacokinetic studies during drug development and for medication prescribing .…”

“…In 2011, the CKD‐EPI equation was adapted for cystatin C (CKD‐EPI Cys ), and this equation is thought to be more accurate in patients with low body mass index . However, a 2012 version of CKD‐EPI combining both creatinine and cystatin C (CKD‐EPI Comb ) is regarded by many as the most accurate estimator of kidney function in community‐dwelling older populations . Two more eGFR equations were developed specifically for older patients by the Berlin Initiative Study (BIS) based on creatinine (BIS Cr ) or a combination of creatinine and cystatin C (BIS Comb ), and it has recently been suggested that these equations are the most accurate in elderly populations .…”

Longitudinal Changes in Kidney Function Estimated from Cystatin C and Its Association with Mortality in Elderly Women

“…While lacking detailed medical histories, we can only speculate on whether a concurrent illness such as acute kidney injury or hemodynamic change caused a transient increase in the eGFR. However, the cross-sectional point prevalence of CKD cysC appears to be higher in the OPRA cohort than other studies, possibly due to the heterogeneity of other populations, especially regarding age span, analytical methods, and study equations [16,[24][25][26]. Environmental and lifestyle factors may also affect CKD prevalence between countries [27].…”

“…To counterbalance this, we also chose CAPA cysC [22], which did include elderly subjects in its development. Likely, it performs better than CKD-EPI cysC in this age-group [24,25]. Furthermore, another equation using cysC is Full Age Spectrum equation (FAS), showing comparable performance as CAPA [30].…”

Does Beta-Trace Protein (BTP) Outperform Cystatin C as a Diagnostic Marker of Acute Kidney Injury Complicating the Early Phase of Acute Pancreatitis?

“…As a marker of glomerular filtration, serum BTP may have an advantage over serum cystatin C in patients treated with glucocorticoids, including those after renal transplantation [1]. On the other hand, recent study that compared serum BTP with serum cystatin C in elderly patients showed better correlation of cystatin C based estimated glomerular filtration rate with measured filtration rate [38].…”