Objective: Chronic kidney disease (CKD) markedly increases cardiovascular morbidity and mortality, with coronary artery calcification (CAC) as a central pathophysiologic feature. Early identification of subclinical cardiovascular damage remains a clinical priority, as traditional measures—serum creatinine, eGFR, and albuminuria—often rise only after substantial nephron loss. The objective of this study is to synthesize current evidence on emerging imaging and biochemical biomarkers capable of detecting early cardiovascular and renal injury in CKD, emphasizing the translational potential of cardiac magnetic resonance (CMR)-derived myocardial tissue markers—native T1, extracellular volume fraction (ECV), and left ventricular strain—and their integration with circulating biomarkers reflecting inflammation, fibrosis, and metabolic dysregulation.

Methods: A comprehensive analytical review was conducted using data from major cohort studies and meta-analyses published between 2010 and 2025, focusing on markers predictive of CKD progression and cardiovascular events. Biomarkers were grouped into:

1.       CMR-based myocardial indices (T1 mapping, ECV, strain imaging);

2.       Inflammatory and tubular injury markers (KIM-1, NGAL, suPAR, sTNFR1/2); and

3.       Metabolic and vascular markers (Cystatin C, UACR, miRNAs, NT-proBNP, hs-Troponin T/I).

Inclusion criteria required human studies with defined CKD stages, validated imaging or laboratory assays, and adjustment for conventional risk factors (age, diabetes, hypertension, lipid profile, and eGFR). When available, pooled estimates and effect sizes from systematic reviews were summarized to illustrate predictive strength and reproducibility. This synthesis aimed to identify biomarkers or multimodal combinations offering practical diagnostic value for clinical or research application in CKD-associated cardiovascular disease.

Results:

1. CMR-derived myocardial tissue biomarkers:

Advanced CMR techniques quantify diffuse myocardial fibrosis and early ventricular dysfunction, both common in CKD even in the absence of overt heart disease. Across multicenter cohorts, native T1 and ECV values consistently correlated with left ventricular mass index, CAC burden, and adverse outcomes. Each 10 ms increment in native T1 corresponded to roughly a 1.1- to 1.3-fold increase in odds of moderate CAC (Agatston > 100 AU), independent of age and diabetes. Reduced global longitudinal strain (GLS) similarly predicted higher CAC and mortality, outperforming ejection fraction in sensitivity to early remodeling.

2. Inflammatory and tubular injury markers:

Plasma KIM-1 emerged as one of the strongest predictors of CKD onset and progression, with a doubling in concentration linked to ~50 % increased CKD risk in long-term follow-up cohorts. suPAR and sTNFR1/2 independently predicted eGFR decline and cardiovascular death, underscoring the contribution of chronic inflammation to cardio-renal deterioration. NGAL, although initially validated for acute kidney injury, showed prognostic value in chronic stages and correlated with CMR-derived myocardial fibrosis indices, suggesting a shared inflammatory-fibrotic pathway.

3. Metabolic and vascular stress markers:

Serum Cystatin C improved detection of early renal function loss compared with creatinine, particularly in elderly or sarcopenic patients. Urine albumin (UACR), while established, retained additive prognostic power when combined with inflammatory or imaging biomarkers. Circulating microRNAs (e.g., miR-21, miR-29, miR-192-5p) demonstrated pooled diagnostic accuracy with sensitivity ≈ 0.86 and specificity ≈ 0.79 for CKD presence; urinary panels achieved AUC ≈ 0.92. Furthermore, inclusion of cardiac biomarkers—NT-proBNP and high-sensitivity troponin—enhanced prediction of cardiovascular mortality in CKD cohorts, even after adjustment for renal function.

4. Interaction with comorbidities:

Comorbid diabetes mellitus and hypertension amplified biomarker expression and accelerated both renal and coronary pathology. Elevated TNFRs and KIM-1 levels independently forecasted faster eGFR decline and greater CAC in diabetic CKD. Similarly, hypertensive CKD patients exhibited higher native T1 and ECV values, consistent with pressure-induced interstitial fibrosis. These findings support the concept of a cardio-renal-metabolic continuum, in which vascular inflammation and myocardial fibrosis coexist early and progress jointly.

5. Multi-marker integration:

Combining a small set of top-performing biomarkers yielded strong discriminative ability. For instance, a model including sTNFR1, sCD40, and a collagen-derived urinary peptide achieved a C-index ≈ 0.86 for kidney failure prediction, exceeding UACR alone (0.71). Parallel multimodal models integrating CMR fibrosis metrics with inflammatory biomarkers showed potential to identify subclinical cardiovascular damage before symptomatic heart disease develops.

Discussion: This synthesis highlights the convergence of imaging and molecular biomarkers as a transformative approach to early detection of cardiovascular and renal risk in CKD. CMR provides non-invasive quantification of myocardial fibrosis and ventricular strain, while plasma and urinary markers capture complementary systemic and renal inflammatory activity. Together, these indices characterize the multi-organ pathophysiology underlying CAC development and heart-kidney interaction.

From a translational perspective, these findings have several practical implications:

Clinical      integration: Combining CMR-derived myocardial fibrosis markers (native T1,      ECV, GLS) with circulating injury and inflammatory biomarkers could yield      a sensitive diagnostic algorithm for identifying CKD patients at greatest      risk of coronary calcification and heart failure.

Risk      stratification and monitoring: Multi-marker panels enable individualized      risk profiling and may guide intensity of cardiovascular prevention,      dialysis initiation timing, or imaging surveillance.

Research      direction: Future prospective studies should validate standardized      cut-offs for CMR indices in CKD, evaluate longitudinal changes alongside      biomarker trajectories, and test whether therapeutic modulation of      inflammation or fibrosis attenuates CAC progression.

In conclusion, the integration of quantitative CMR and molecular biomarkers offers a scientifically robust and clinically practical avenue for earlier recognition of cardio-renal injury. Emphasizing multi-system assessment rather than single-organ metrics aligns with precision medicine goals and the conference’s theme of innovative, translational cardiovascular science.