Discrepancies between Cystatin C–Based and Creatinine-Based eGFR

Abstract

Background: Recent guidance suggests clinicians increase use of cystatin C for the estimation of glomerular filtration rate. Discrepant levels of creatinine vs. cystatin C-based estimated glomerular filtration rate (eGFRcr vs eGFRcys) can occur and might signify inaccurate estimation of eGFR using creatinine alone. This study sought to enhance the knowledge of the risk factors and clinical implications of having a large eGFR discrepancy. Methods: Participants in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study of US adults followed over 25 years. eGFR discrepancy was measured at five clinical visits and defined as eGFRcys either 30% lower or higher than eGFRcr, the current clinical standard of care. The associations between eGFR discrepancies and kidney-related laboratory parameters were assessed using linear and logistic regression and long-term adverse outcomes, including kidney failure, acute kidney injury, heart failure and death, using Cox proportional hazards models. Results: Among 13,197 individuals (mean age 57 (SD 6) years, 56% women, 25% Black race), 7% had eGFRcys 30% lower than eGFRcr at Visit 2 (1990-1992), and this proportion increased over time to 23% by Visit 6 (2016-2017). In contrast, the percent with eGFRcys 30% higher than eGFRcr was relatively stable (3% to 1%). Independent risk factors for having eGFRcys 30% lower than eGFRcr included older age, female sex, non-Black race, higher eGFRcr, higher BMI, weight loss, and current smoking. Those with eGFRcys 30% lower than eGFRcr had more anemia and higher uric acid, FGF23, and phosphate levels as well as higher risk of subsequent mortality, kidney failure, acute kidney injury, and heart failure compared to those with similar eGFRcr and eGFRcys values. Conclusions: Having eGFRcys lower than eGFRcr was associated with worse kidney-related laboratory derangements and a higher risk of adverse health outcomes.

Discordance Between Creatinine-Based and Cystatin C–Based Estimated GFR: Interpretation According to Performance Compared to Measured GFR

“…Second, study participants included ambulatory patients without severe comorbid conditions. The proportion of patients with large negative eGFRdiff might be expected to be higher among ambulatory patients with more extensive comorbid conditions as well as among hospitalized patients where the relative impacts of non-GFR determinants on creatinine and cystatin C could differ from our study, 63 , 64 , 65 although the recent studies in general population samples provide support for these findings in the general clinical population. 56 Future studies in large community-based populations and in clinical populations, with more extensive burden of comorbidity, including hospitalized patients, can provide more specific information for indications for cystatin C measurement.…”

The Difference Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and Risk of Diabetic Microvascular Complications Among Adults With Diabetes: A Population-Based Cohort Study

“…The mechanisms underpinning the connection between eGFRdiff and risk of DMCs remain inadequately understood. In our results, participants with large negative eGFRabdiff demonstrated higher levels of inflammatory marker and BMI, more ever smokers, and higher prevalence of hypertension and cardiovascular history, consistent with previous studies ( 18 , 24 ). These factors are all well-documented risk factors of DMCs.…”

“…To date, a few studies have revealed significant association between eGFRdiff and kidney outcomes among diverse specific populations. For example, in 13,197 individuals in the Atherosclerosis Risk in Communities Study and in 158,601 adults in the Stockholm Creatinine Measurements project, large negative eGFRdiff was associated with higher risk of end-stage kidney disease and acute kidney injury ( 12 , 18 ). Similarly, large negative eGFRdiff has also been found to be associated with increased risk of worsening kidney function in patients with heart failure ( 13 ).…”

Association of Ratio of eGFR by Cystatin C and Creatinine with Mortality in Heart Failure

“… 2 Emerging data demonstrate that large intraindividual discrepancies between eGFRcr and eGFRcys are associated with adverse outcomes. 3 , 4 A ratio of eGFRcys/eGFRcr <0.7, indicating an intraindividual eGFRcys >30% lower than eGFRcr, has been associated with greater mortality risk in the general population. 3 In a post hoc analysis of the Prospective Comparison of ARNI [Angiotensin Receptor - Neprilysin Inhibitor] with ACEI [Angiotensin-Converting - Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial consisting of patients with predominantly moderate HFrEF, large discrepancies between eGFRcr and eGFRcys were associated with higher mortality.…”

“…A comparison was also made between participants with eGFRcys/eGFRcr <0.7 versus ≥0.7, given its association with mortality in the general population. 3 Individual Cox proportional hazards models were constructed to test the association between baseline eGFRcr, eGFRcys, eGFRcr-cys, and eGFRcys/eGFRcr <0.7 and all-cause mortality. The proportional hazards assumption was assessed using Schoenfeld residuals.…”