# Comparison of Creatinine-, Cystatin C-, and Combined Creatinine–Cystatin C-Based Equations for Estimating Glomerular Filtration Rate: A Real-World Analysis in Patients with Chronic Kidney Disease

**Authors:** Joško Osredkar, Iza Klemenčič, Kristina Kumer, Jernej Pajek, Bojan Knap

PMC · DOI: 10.3390/ijms27010364 · International Journal of Molecular Sciences · 2025-12-29

## TL;DR

This study compares different methods for estimating kidney function and finds that combining creatinine and cystatin C provides the most accurate results for diagnosing chronic kidney disease.

## Contribution

The study demonstrates that the combined creatinine–cystatin C equation improves diagnostic accuracy compared to creatinine- or cystatin C-based equations alone.

## Key findings

- The combined CKD-EPI equation aligned with clinical diagnosis in all CKD cases.
- eGFRcr overestimated kidney function in 10/16 patients, while eGFRcysC underestimated in 8/16.
- Switching from eGFRcr to eGFRcr-cysC led to reclassification in 9/16 patients.

## Abstract

The estimated glomerular filtration rate (eGFR) is a cornerstone of kidney function assessment. Widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine (eGFRcr), cystatin C (eGFRcysC), or both (eGFRcr-cysC) are influenced by non-glomerular filtration rate (GFR) factors, and their performance may vary across clinical contexts. We retrospectively analyzed 435 adult patients with simultaneous serum creatinine and cystatin C measurements. eGFR was calculated using CKD-EPI 2021 (creatinine), CKD-EPI 2012 (cystatin C), and CKD-EPI 2021 (combined) equations. Patients were classified into Kidney Disease: Improving Global Outcomes (KDIGO) GFR categories (G1–G5), and discrepancies between equations were identified. 44 patients (10.1%) showed discordant GFR categorization across all three equations and underwent detailed clinical assessment. 16 of the 44 discordant cases had clinically confirmed chronic kidney disease (CKD). The combined equation aligned with the clinical diagnosis in all CKD cases. eGFRcr overestimated kidney function in 10/16 patients, while eGFRcysC produced lower values in 8/16, consistent with early CKD but potentially influenced by inflammation or obesity. Reclassification occurred in 9/16 patients when switching from eGFRcr to eGFRcr-cysC, including four who shifted from G2 to G3a–G4. A significant difference was observed between eGFRcr and eGFRcr-cysC (p < 0.05). The combined CKD-EPI equation demonstrated the best clinical concordance, supporting its broader use when diagnostic accuracy is essential.

## Linked entities

- **Diseases:** chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}
- **Diseases:** inflammation (MESH:D007249), obesity (MESH:D009765), CKD (MESH:D051436), Kidney Disease (MESH:D007674)
- **Chemicals:** Creatinine (MESH:D003404)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12786158/full.md

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Source: https://tomesphere.com/paper/PMC12786158