In the first 36 months of the PRIME-CKD project, significant progress has been made; we completed the first clinical PRIME-CKD study (UVALID), designed for the validation of the pharmacodynamic response biomarkers (WP1). Furthermore, in existing clinical trials (WP2), we validated uCLU as a pharmacodynamic biomarker for assessing treatment response to atrasentan in the data of the SONAR-, Spartan- and PROTECT trials. We have shown that uEGF was significantly associated with lower risk of kidney disease progression in patients with T2D with and without CKD in the CANVAS, CREDENCE, CANPIONE, DAPA-CKDtrials. We then advanced the validation of uEGF in clinical practice databases and completed the measurement of uEGF in the German CKD cohort in 5000 participants. With the completion of more than 30000 urinary clusterin and EGF measurements, we finalized work package 2 and completed the retrospective validation of the two biomarkers. Several scientific papers are published, in press or in development describing the results and implication of the findings to support implementation of these biomarkers in clinical practice.
We demonstrated that a cut-off for response of -30% for uCLU and 0% for uEGF is an optimal response threshold, which seems clinically applicable. This evidence currently proves the efficacy of treatment to the clinicians and patients in our upcoming clinical trials. These thresholds form a future basis for the evidence-based tools for clinical implementation and are thus crucial for holistic roadmap for clinical practice implementation. Two PRIME-CKD partners (RENALYTIX (REN) and REGIONH (STENO)) have announced a partnership to implement a new biomarker risk algorithm in all REGIONH (STENO) practices in Denmark. This is a big step forward in achieving a personalized medicine approach for patients with CKD and a prime example for how the PRIME-CKD consortium provides clinicians and patients with evidence-based tools to personalize medicine.
PRIME-CKD has actively participated and contributed to the companion diagnostics community, reaching out to researchers, healthcare providers and companies globally with the establishment of the PRIME-CKD Stakeholder Network. As an example, consortia members support with validated procedures, data and experience a diagnostic company that develops a new assay to measure the Glycocalyx. Additionally, advice and consultancies have been given to various start-ups pharma companies in Europe as well. Through the stakeholder network we have been able to secure finerenone medication for free for the CKD Biomatch study in WP3. The extensive networks of the project partners have facilitated the already existing personal and business accounts to reach diverse stakeholder groups. PRIME-CKD scientists have started to work on a roadmap and are collecting experiences with respect to diagnostics and biomarker validation to present this to stakeholders at the completion of the project.
