PRIME-CKD addresses a key barrier in improving care for people with chronic kidney disease (CKD): the lack of reliable, clinically validated biomarkers to guide personalized treatment. Although CKD affects around 10% of adults worldwide and effective therapies now exist, patients respond very differently to these treatments, leaving many without optimal benefit.

For successful clinical implementation of biomarkers rigorous analytical validation is a crucial and often underestimated prerequisite. This includes assessing how stable these biomarkers are over time, how much they vary within individuals at different time points, and how storage conditions of samples may influence measurements.

Urinary epidermal growth factor (uEGF) and urinary clusterin (uCLU) are promising  biomarkers in chronic kidney disease (CKD). PRIME-CKD researchers have evaluated the intra-individual stability and long term stability of EGF and CLU in urine samples in the UVALID study. They have now published their results in the International Journal of Molecular Sciences.

In the UVALID study uEGF and uCLU levels were determined in urine samples that were collected from 60 patients with CKD at three time points over the course of an 8 week period. The samples were collected from different locations, and analyzed in three different laboratories: the University Medical Center in Groningen, Steno Diabetes Center in Copenhagen and the University Medical Center Hamburg-Eppendorf. Samples were stored for up to 15 months at -20 and -80 °C to assess the stability of uEGF and uCLU.

The outcome of the UVALID study gives important insight into the scope and limitations of using  uEGF and uCLU as pharmacodynamic biomarkers that can monitor treatment response and help tailor therapy to individual CKD patients.

Erik Moedt, PhD candidate at the University Medical Center Groningen (NL) explains:

“It is very interesting to see the differences between measurements of uEGF and uCLU in the UVALID study. uEGF demonstrated low variability and remained stable after long-term storage at both  -20 and -80 °C.

In contrast, uCLU was less stable at -20 °C but its stability was preserved at -80 °C. We have observed pH effects on the variability of the uCLU samples and a lower inter-laboratory reproducibility, especially at low concentrations.

Dr. Elisabeth Meister, MD and clinician scientist at the III. Department of Medicine and Hamburg Center for Kidney Health, University Medical Center Hamburg Eppendorf adds:

“The UVALID results exactly underscore the need for rigorous analytical validation of pharmacodynamic biomarkers. In this study we have learned vital lessons on the reliability of measurement of uEGF and uCLU in urine samples of CKD patients.

 uEGF has shown robust analytical performance, supporting its potential clinical applicability in CKD. On the other hand, uCLU exhibited important analytical limitations that call for further assay optimization to unlock its full potential.”

What this may mean in practice
Personalized medicine could help kidney patients to receive effective therapy sooner. By implementing biomarker-guided therapy, clinicians may prevent avoidable kidney disease progression and reduce the likelihood of severe complications such as dialysis.

For healthcare systems, biomarker-guided therapy has the potential to improve treatment efficiency by focusing resources on therapies that offer measurable benefit. This could support future decision-making for reimbursement, guideline development and long-term kidney-health strategies.