Assessment of kidney function for ensuring correct drug dosage
The kidneys are an important site of elimination for most medications and their metabolites. For this reason, an accurate assessment of kidney function is critical for ensuring correct dosage.
Chemotherapeutic agents and antibiotics are two classes of drugs for which an accurate understanding of a patient's renal function is particularly important. Whether they are conventional cytotoxic agents or molecularly targeted therapies, chemotherapy drugs are known to affect nephrons and renal microvasculature with clinical manifestations ranging from electrolyte disturbances and proteinuria to acute kidney injury (AKI) and progression of chronic kidney disease (CKD)1.
Similarly, high concentrations of antibiotics like vancomycinare associated with AKI and ototoxicity while concentrations below the therapeutic threshold could lead to treatment failure and a risk of developing bacterial resistance2,3.
eGFR and kidney function
Estimated Glomerular Filtration Rate (eGFR) (link) is the most commonly used parameter for assessing a patient's kidney function. The equations widely used to calculate eGFR consider a patient's plasma/serum concentration of creatinine along with demographic factors such as race, sex, and age4.
The primary issue with the majority of these formulas is that they were derived from studies that involved homogenous patient populations. For instance, the Cockcroft Gault equation cited in most package inserts provided by pharmaceutical manufacturers, was developed in 1976 based on creatinine clearance data from a population of 249 white males5.
Similarly, the Modification of Diet in Renal Disease (MDRD) study from which the MDRD formula was derived, only included patients with renal disease6. When the aforementioned is considered in combination with creatinine's dependence on muscle mass, it is easy to see why a growing body of research supports the clinical implementation of cystatin C-based dosing algorithms.
Cystatin C and creatinine in medication dosing protocols
The case for using cystatin C in addition to creatinine in medication dosing protocols is best made in a study published by the Mayo clinic, where a novel cystatin C and creatinine based vancomycin dosing algorithm (intervention) was compared to the standard approach (control) of calculating dose according to estimated creatinine clearance7.
Greater accuracy of antibiotic dosing
In this study, investigators found that 50 % of patients in the intervention arm of the study achieved a vancomycin dose within the therapeutic range compared to only 28 % in the control arm7. Additionally, patients who received the antibiotic according to the new algorithm achieved the desired dosage 25 % faster than patients following the standard approach7. This has broader implications for the level of care delivered at the institution because earlier identification of inadequate concentrations of the antibiotic would enable clinicians to either increase the dose or identify a more suitable therapeutic intervention7.
Co-reporting of cystatin C and creatine based eGFRs for adjustment of chemotherapy doses
A similar study published earlier this year (2021) by researchers at Marien hospital in Germany explored the benefits of adjusting cancer treatment doses according to a protocol that involved the co-reporting of cystatin C and creatine based eGFRs4. By providing personalised dosing regimens for those patients whose cystatin C-based eGFR differed from their creatinine-based eGFR by more than 15 ml/min/1.73m2, drug doses were lowered in 6.2 % of patients in the study population4.
Such a reduction is estimated to deliver 105,000€per yearin savings from direct drug costs alone4. Given the 1800€cost associated with performing cystatin C testing for the 606 patients in the study, the authors further pointed out that the benefit: Cost ratio of performing the test within the oncology unit would be 58:14. What is noteworthy here is that this cost-benefit analysis does not capture the value provided in-terms of increased physician confidence and increased patient satisfaction owing to side-effect avoidance.
Better outcomes at a lower cost
As the pace and pressure to embrace value-based care picks up globally, cystatin C could prove to be a valuable diagnostic tool for ensuring better patient outcomes at lower costs.
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Webinar about drug dosing and cystatin C
Santos, MLC et al. Nephrotoxicity in cancer treatment: An overview, in World J Clin Oncol, 2020. 11(4): p. 190-204.
Frazee, EN et al. Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study, in Crit Care, 2014. 18(3): p. R110.
Begg, EJ, ML Barclay and CJ Kirkpatrick. The therapeutic monitoring of antimicrobial agents, in Br J Clin Pharmacol, 1999. 47(1): p. 23-30.
Hoenle, A et al. Avoiding insufficient therapies and overdosing with co-reporting eGFRs (estimated glomerular filtration rate) for personalized drug therapy and improved outcomes - a simulation of the financial benefits. EJIFCC, 2021. 32(1): p. 41-51.
Cockcroft, DW and MH Gault, Prediction of creatinine clearance from serum creatinine. Nephron, 1976. 16(1): p. 31-41.
Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247-254.
Frazee, E et al. Cystatin C-Guided Vancomycin Dosing in Critically Ill Patients: A Quality Improvement Project. Am J Kidney Dis, 2017. 69(5): p. 658-666.
Gentian Diagnostics AS published this content on 08 April 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 08 April 2021 11:53:07 UTC.