Prognosis and Personalized In Silico Prediction of Treatment Efficacy in Cardiovascular and Chronic Kidney Disease: A Proof-of-Concept Study

Abstract

(1) Background: Kidney and cardiovascular diseases are responsible for a large fraction of population morbidity and mortality. Early, targeted, personalized intervention represents the ideal approach to cope with this challenge. Proteomic/peptidomic changes are largely responsible for the onset and progression of these diseases and should hold information about the optimal means of treatment and prevention. (2) Methods: We investigated the prediction of renal or cardiovascular events using previously defined urinary peptidomic classifiers CKD273, HF2, and CAD160 in a cohort of 5585 subjects, in a retrospective study. (3) Results: We have demonstrated a highly significant prediction of events, with an HR of 2.59, 1.71, and 4.12 for HF, CAD, and CKD, respectively. We applied in silico treatment, implementing on each patient’s urinary profile changes to the classifiers corresponding to exactly defined peptide abundance changes, following commonly used interventions (MRA, SGLT2i, DPP4i, ARB, GLP1RA, olive oil, and exercise), as defined in previous studies. Applying the proteomic classifiers after the in silico treatment indicated the individual benefits of specific interventions on a personalized level. (4) Conclusions: The in silico evaluation may provide information on the future impact of specific drugs and interventions on endpoints, opening the door to a precision-based medicine approach. An investigation into the extent of the benefit of this approach in a prospective clinical trial is warranted.

Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology

“…In a recent study, urinary peptides were shown to predict responses to BP medication [47]. Using the identified peptide changes, along with the predicted impact of intervention on urinary peptides [5], might help personalize intervention and ultimately select the most appropriate therapy.…”

“…T he increasing burden of chronic diseases indicates the need for noninvasive, easily accessible, stable, and cost-effective biomarkers. The field of urinary proteomics/peptidomics has developed extensively and consistently over the past two decades, with a focus on kidney and cardiovascular diseases [1][2][3][4][5][6]. Thousands of proteins present in the human body are ultimately degraded by ubiquitous proteolytic enzymes, resulting in the generation of protein fragments, that is, peptides.…”

Association of urinary peptides with hypertension

“…Along these lines, in a recent manuscript urinary peptides were shown to predict the response to blood pressure medication 51 . Using the identified peptide changes along with the predicted impact of intervention on urinary peptides 52 might help towards personalizing intervention and ultimately selecting the most appropriate therapy.…”

Mortality risk in survivors of acute COVID-19 and the urinary proteome: Follow-up results from a multinational study that prospectively evaluated a proteomic urine test for early and accurate prognosis of critical course complications in patients with SARS-CoV-2 infection (CRIT-COV-U)

“…These peptides serve as early indicators of the likelihood of mortality, providing valuable insights into the underlying pathophysiological mechanisms driving adverse outcomes in COVID-19 patients. By leveraging these predictive biomarkers, healthcare professionals can proactively identify individuals at elevated risk of mortality and implement targeted interventions aimed at mitigating this risk, thereby potentially altering the trajectory of the disease course, like already showed for chronic kidney and heart diseases 8 .…”