The slower turnaround time for cystatin C relative to creatinine is a problem also, she said. “If you do send it out, that cystatin C eGFR will not be concurrently available with creatinine.” The delay creates a barrier to calculating an eGFR using the combined 2021 CKD-EPI creatinine-cystatin C equation, Dr. Karger said. “So it’s a challenge to take a result from an outside lab and your internal lab and then result an eGFR.”
What should be done to facilitate more widespread use of cystatin C testing? Dr. Karger suggests the following 10 strategies for manufacturers and laboratories:
- Increase availability of cystatin C on common clinical chemistry analyzers. “I would encourage instrument manufacturers to develop or package existing cystatin C assay reagents,” Dr. Karger said. Some major instrument manufacturers that do not manufacture their own reagents are partnering with open channel reagent manufacturers to package those reagents as their own, she said, “but there’s still progress that can be made to make it widely available.”
- Manufacturers should update their marketing approach to present cystatin C as an emerging routine test rather than a specialty test.
- Manufacturers should continue to improve assay harmonization and precision.
- Lower the reagent costs of cystatin C. As test use rises, reagent costs will decline, “so the more you use it, the lower the cost will be.” But the more complex methodology for cystatin C assays means the costs will not get down to as low as they are for creatinine.
- Advocate for third-party reimbursement and reduced requirements for Medicare reimbursement.
- Promote the 2024 KDIGO guideline with its broadened ration-ale for use of cystatin C to increase testing volume and help justify reimbursement.
- Partner with clinical teams, like nephrology and pharmacy, to jointly promote evidence-based utilization. “The resultant increase in test volumes can make in-house testing financially sustainable.” In-house testing makes it possible, too, to provide a turnaround time comparable to that of creatinine, so the cystatin C result would be more useful in real time and both results could be used concurrently.
- Consider a staged rollout of cystatin C testing by limiting initial ordering to ICU units and/or for renal drug dosing. “Expand testing availability beyond that once you feel you can successfully launch on a smaller scale.”
- Educate providers on how to interpret discrepancies between cystatin C and creatinine, when to use cystatin C instead of creatinine, and the role of non-GFR determinants, which impact both cystatin C and creatinine.
- Create electronic health record-based tools to facilitate the visualization of both creatinine- and cystatin C-based GFR estimates. “We shouldn’t go live with a test and not think about how it’s seen by our end users,” Dr. Karger noted.
At M Health Fairview and in other institutions, when cystatin C is newly implemented, nonordering providers may not know to look for the result because typically it is not ordered as often as creatinine. “We’ve had situations where patients had a cystatin C eGFR that was disparate from the creatinine eGFR. The provider didn’t know to look for the cystatin C eGFR,” she said, and having seen the discrepancy would have changed decision-making. Plans are underway to implement an alert to providers for pending or resulted cystatin C for orders for renally dosed drugs, IV contrast, or transplant-related care.
Dr. Karger and coauthor Michael Shlipak, MD, MPH, of the University of California San Francisco, in a 2025 review article on GFR estimation with cystatin C, wrote that the NKF-ASN Task Force recommendation and the 2024 KDIGO guideline can provide a “springboard” for clinician stakeholders and clinical laboratories to partner to educate their clinical providers on best practices for use of cystatin C and to promote greater use of the test, which they say can then provide the financial incentive to bring the test in-house (Karger AB, et al. Clin Chem. 2025;71[7]:743–751). And that, they write, can make it possible to achieve “seamless implementation of eGFR reporting with a combined creatinine-cystatin C equation.”
Amy Carpenter is CAP TODAY senior editor.