Adding urinary biomarkers to the kidney failure risk equation (KFRE) may improve the prediction of chronic kidney disease (CKD) progression.

The current 4-variables KFRE is based on age, sex, glomerular filtration rate (GFR), and urinary albumin to creatinine ratio (UACR). Although GFR and UACR are established markers of CKD progression, these markers appear “relatively late in the course of CKD and reflect more the functional changes than the early structural alterations in the kidney,” explained Frank Bienaimé, MD, of Service d’Explorations Fonctionnelles, Hôpital Necker Enfants Malades in Paris, France, and colleagues.

Among 24 molecules associated with kidney fibrosis, inflammation, cell proliferation, angiogenesis, oxidative stress, and tubular damage, the investigators found that the combination of 5 biomarkers improved the prediction of CKD progression beyond the KFRE. These included chemokine C-C motif ligand 2 (CCL2), epidermal growth factor (EGF), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL), and transforming growth factor-α (TGF-α). Current commercial assays (ELISA) were able to quantify these molecules in urine using FDA-approved validation criteria.

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In models discriminating between fast and slow CKD progressors, the mean areas under the curve based on KFRE with than without these biomarkers were 0.722 vs 0.682, respectively, the investigators reported in eBioMedicine.

After full adjustment, the odds for rapid CKD progression were 3.0-, 1.9-, 1.9-, and 1.1-fold higher with TGF-α, albumin, CCL2, and KIM1, respectively, Dr Bienaimé’s team reported. EGF and NGAL predicted 57%, and 45% decreased odds for rapid progression, respectively. All results were significant except for KIM1.

The investigators defined slow vs fast progression using 10% decline in measured GFR per year as a cutoff. They tested urine samples from 229 patients with CKD within the NephroTest cohort (mean age, 61 years) who had their GFRs measured by chromium-51 labelled ethylenediaminetetraacetic (EDTA) clearance.

According to Dr Bienaimé’s team, the study findings support combined use of rigorously validated biomarkers to increase the predictive accuracy for GFR decline. Future studies including larger, representative CKD populations are needed to further validate these findings.

Disclosure: This research was partly supported by Roche Laboratories. Please see the original reference for a full list of disclosures.


Bienaimé F, Muorah M, Metzger M, et al. Urinary biomarkers of CKD progression which combination may improve the prediction of CKD progression. EBioMedicine. 93:104635. doi:10.1016/j.ebiom.2023.104635