Comment on: Difference between kidney function by cystatin C versus creatinine and association with muscle mass and frailty

Abstract

We are writing to share some constructive thoughts on the recent study examining estimated glomerular filtration rate (eGFR), muscle mass, and frailty among older adults.¹ Although the study provides valuable insights, I believe there are several methodological considerations that could be addressed to further strengthen the findings.

First, the study employs eGFR formulas based on serum creatinine and cystatin C, both of which have inherent limitations and assumptions that may not hold true across diverse populations. Specifically, the creatinine-based eGFR formula assumes a constant creatinine generation rate, which can vary significantly with muscle mass and dietary intake. Individuals with higher muscle mass typically have elevated creatinine levels, potentially leading to an underestimation of eGFR.² On the other hand, cystatin C-based eGFR, though less influenced by muscle mass, can be affected by factors such as inflammation, smoking, and corticosteroid use. These variables can introduce variability and potential bias in eGFR estimates. Moreover, discrepancies in calibration standards for cystatin C assays across different laboratories may lead to inconsistent results.³

Second, the study does not extensively address the role of comorbidities, which could confound the relationships between kidney function, muscle mass, and frailty. For instance, cardiovascular diseases can lead to reduced renal perfusion and muscle wasting due to chronic inflammation and diminished physical activity.⁴ Similarly, diabetes can cause muscle loss through mechanisms such as insulin resistance and chronic inflammation.⁵ Chronic inflammatory conditions like rheumatoid arthritis or chronic obstructive pulmonary disease (COPD) also impact eGFR and muscle mass through sustained inflammation and reduced physical activity.⁵ Incorporating these comorbidities into the analysis would provide a more comprehensive understanding of the observed associations.

Third, the reliance on single measurements of eGFR and muscle mass is another critical limitation. Kidney function and muscle mass can fluctuate due to various factors such as acute illnesses, hydration status, or temporary changes in diet and physical activity.⁶ Single measurements may not accurately reflect the average or typical status of these parameters. Longitudinal data would be more informative, allowing researchers to observe changes over time and establish more robust causal relationships between muscle mass and kidney function.

Fourth, although the study focuses on frailty and muscle mass, it does not evaluate functional outcomes, which are crucial for understanding the clinical implications of the findings. Functional outcomes such as mobility, balance tests, and activities of daily living (ADLs) provide direct insights into an individual's ability to perform daily activities and their risk of falls or disability.⁷ Furthermore, assessing quality of life through standardized questionnaires can help determine the broader impact of frailty and kidney function on overall well-being. Including these functional measures would enhance the clinical relevance and applicability of the study findings.

In conclusion, addressing these limitations in future research would significantly improve the robustness and generalizability of the findings. Longitudinal studies with comprehensive comorbidity assessments and functional outcome measures are essential for translating physiological insights into meaningful clinical practice and interventions.

Conceptualization: J.D. and J.H. Writing—original draft: J.D. Writing—review and editing: J.H. All authors have read and consented to the publication of this manuscript.

The authors declare no conflicts of interest.

This research was not funded.