Chronic kidney disease (CKD)—now affecting almost one billion people worldwide—demands therapies that can keep pace with its multi-factorial biology. In a new state-of-the-science review published in Biomolecules (Vol. 15, Article 809, June 2025), Sajjad Biglari, Harald Mischak and colleagues pose a decisive question: Should we rely on fixed-dose combination therapy (“polypill”) or move toward biomarker-guided personalised intervention?

Why this matters

CKD progression is driven by intersecting pathways—fibrosis, metabolic stress, haemodynamic overload and inflammation—so a single drug seldom suffices.

Modern “backbone” agents (SGLT2 inhibitors, non-steroidal MRAs, GLP-1 receptor agonists) already slow eGFR decline and curb cardiovascular risk.

Urinary-peptide classifiers (e.g., CKD273) now forecast renal or cardiac events years in advance, opening the door to precision escalation—or de-escalation—of therapy.

What the review highlights

Early combination regimens look powerful. Pilot trials that layer an SGLT2 inhibitor with finerenone (or add a GLP-1 RA) achieve > 50 % albuminuria reduction while mitigating hyperkalaemia risk. Yet cost and pill-burden remain hurdles.

Biomarker-guided treatment promises “right-patient-right-drug”. Risk classifiers can flag who is likely to benefit most from RAAS blockade, SGLT2i or MRA therapy, potentially sparing low-risk patients unnecessary exposure and expense.

A hybrid paradigm may win out. The authors envision a low-cost ARB + SGLT2i scaffold, fine-tuned by biomarker trends over time—a concept that dovetails with the PICKED network’s modelling work.

Read the full article

🔗 DOI: 10.3390/biom15060809

This research is supported by the PICKED project (HORIZON-MSCA-2023-DN-01, 101168626) and other European initiatives that are shaping the future of precision nephrology.