Using Cystatin C and Clinical Judgment to Dose Medications in Special Populations

In this National Kidney Foundation (NKF) panel, Andrew Bzowyckyj, PharmD, BCPS, CDCES, senior scientific director and learning consultant at NKF, is joined by nephrology pharmacists:

• Rachel Khan, PharmD, associate professor of internal medicine and nephrology at the Virginia Commonwealth University School of Pharmacy;
• and Joanna Hudson, PharmD, BCPS, FASN, FCCP, professor in the departments of clinical pharmacy and translational science and medicine with an emphasis in nephrology at the University of Tennessee Health Sciences.

In the final installment the NKF panel, the experts describe how to apply estimated glomerular filtration rate (eGFR)-based dosing in older adults and in patients with obesity or low body weight. Hudson notes that contemporary eGFR equations were developed in larger, more diverse populations than the Cockcroft-Gault equation, which was derived from about 250 predominantly male participants. However, they still do not fully represent these outlier groups. In older adults, reduced muscle mass can make creatinine an unreliable marker. Hudson recommends pharmacists should weigh whether a drug has a narrow or wide therapeutic index and, in select cases, consider measuring creatinine clearance or GFR, while acknowledging the logistical challenges.

Khan says eGFR equations that use cystatin C alone or combined with creatinine are appropriate for drug dosing and can be BSA-adjusted in the same way as creatinine-based equations, because the goal is the most accurate estimate of kidney function. She cautions that cystatin C is not automatically more accurate at extremes of body weight, since weight affects both biomarkers. Citing the KDIGO 2024 guideline, she notes that patients with class 3 obesity or higher may have non-GFR determinants of both creatinine and cystatin C, in which case the combined equation may provide a more balanced estimate.

When creatinine and cystatin C results disagree, Khan says the disagreement itself does not reveal which value is correct. Ideally, both should be drawn at the same time, and clinicians must consider each marker’s non-GFR determinants. She advises making a dosing decision with a plan to monitor for signs that the dose is too high or too low. Hudson points to the panel’s work group paper and NKF resources for guidance on non-GFR determinants. Bzowyckyj adds that emerging research links greater discordance between the 2 markers with worse kidney, acute kidney injury, and cardiovascular outcomes. He closes by inviting clinicians to join the NKF Implementing Medication Decisions with eGFR (IMED eGFR) Community.

Learn more about the National Kidney Foundation at kidney.org and at this link.