# Current Appraisal and Gaps in Knowledge in Cardio–Kidney Metabolic Syndrome Definition

**Authors:** Alberto Palazzuoli, Anna Vittoria Mattioli, Francesco Fedele

PMC · DOI: 10.3390/ijms27041657 · International Journal of Molecular Sciences · 2026-02-08

## TL;DR

This paper reviews the connections between heart, kidney, and metabolic diseases and highlights gaps in understanding and classifying this syndrome.

## Contribution

The paper proposes a diagnostic and laboratory fingerprint to address current challenges in defining cardio-kidney metabolic syndrome.

## Key findings

- Heart failure and kidney dysfunction share a reciprocal relationship, worsening each other's progression.
- Common risk factors like obesity and diabetes contribute to both heart and kidney disease through inflammatory and oxidative pathways.
- Current classification of cardio-kidney metabolic syndrome is hindered by a lack of reliable data on outcomes across disease stages.

## Abstract

Although metabolic, renal, and cardiovascular disorders frequently coexist, little is known about how illness combinations affect prognosis. Cardiovascular disease (CVD), which can manifest as coronary artery disease (CAD), stroke, heart failure (HF), arrhythmias, and sudden cardiac death, is more likely to develop in patients with chronic kidney disease (CKD). This link is closer with regard of heart failure (HF) and renal dysfunction, in which a reciprocal relationship has been demonstrated, with the initial illness of one organ causing the progressive dysfunction of the other system. Common risk factors for both illnesses include obesity, diabetes, metabolic disorders, hypertension, and dyslipemia. Theoretically, each of these factors accelerates the atherosclerotic process or directly damages the endothelium through inflammatory, oxidative, and pro-thrombotic pathways, which in turn causes the beginning of heart dysfunction and renal function deterioration. Although the mechanisms and causes have been identified, there are still a number of unanswered questions regarding classification, development, monitoring, and preventive aspects. Furthermore, the absence of reliable data on cardiac and renal outcomes across different stages contributes to creating confusion in CKM classification and management. This paper discusses the current challenges and perspectives in CKM definition and assessment proposing a specific diagnostic and laboratory fingerprint.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995), coronary artery disease (MONDO:0005010), stroke (MONDO:0005098), heart failure (MONDO:0005252), sudden cardiac death (MONDO:0007264), chronic kidney disease (MONDO:0005300), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** CKM (creatine kinase, M-type) [NCBI Gene 1158] {aka CKMM, CPK-M, M-CK}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, PFN1 (profilin 1) [NCBI Gene 5216] {aka ALS18, PDB7}, HAVCR1 (hepatitis A virus cellular receptor 1) [NCBI Gene 26762] {aka CD365, HAVCR, HAVCR-1, KIM-1, KIM1, TIM}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, ABCD4 (ATP binding cassette subfamily D member 4) [NCBI Gene 5826] {aka ABC41, EST352188, MAHCJ, P70R, P79R, PMP69}, ST2 (suppression of tumorigenicity 2) [NCBI Gene 6761], TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, APOB (apolipoprotein B) [NCBI Gene 338] {aka FCHL2, FLDB, LDLCQ4, apoB-100, apoB-48}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, TNFRSF1B (TNF receptor superfamily member 1B) [NCBI Gene 7133] {aka CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B}, FABP1 (fatty acid binding protein 1) [NCBI Gene 2168] {aka FABPL, L-FABP}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, SERPINA1 (serpin family A member 1) [NCBI Gene 5265] {aka A1A, A1AT, AAT, PI, PI1, PRO2275}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, PLAUR (plasminogen activator, urokinase receptor) [NCBI Gene 5329] {aka CD87, U-PAR, UPAR, URKR}
- **Diseases:** metabolic (MESH:D008659), visceral adiposity (MESH:D007418), CRS (MESH:D003398), obese (MESH:D009765), arrhythmias (MESH:D001145), diastolic dysfunction (MESH:D018487), venous congestion (MESH:D006940), sudden cardiac death (MESH:D016757), stroke (MESH:D020521), overweight (MESH:D050177), acute kidney injury (MESH:D058186), cardiomyopathies (MESH:D009202), calcification (MESH:D002114), tubular damage (MESH:D000230), valve heart diseases (MESH:D006349), endothelial dysfunction (MESH:D014652), diabetes (MESH:D003920), cardiorenal failure (MESH:D051437), CKD (MESH:D051436), cardiovascular, renal, and metabolic syndrome (MESH:D024821), fibrosis (MESH:D005355), Inflammatory (MESH:D007249), injury to (MESH:D014947), dyslipidemia (MESH:D050171), obese metabolic syndrome (MESH:D000067329), deterioration of cardiovascular and renal function (MESH:D018376), hyperuricemia (MESH:D033461), diabetic kidney disease (MESH:D003928), cardiac and renal damage (MESH:D007674), HF (MESH:D006333), collagen (MESH:D003095), T2D (MESH:D003924), cardiac and renal function impairment (MESH:D006331), CAD (MESH:D003324), cardiac remodeling (MESH:D020257), atrial fibrillation (MESH:D001281), CV cardiovascular (MESH:D002318), dilated cardiomyopathy (MESH:D002311), Uremic (MESH:D006463), insulin resistance (MESH:D007333), vascular injury (MESH:D057772), thrombotic (MESH:D013927), albuminuria (MESH:D000419), glomerulosclerosis (MESH:D005921), Cardio-Kidney Metabolic Syndrome (MESH:D059347), vascular calcification (MESH:D061205), atherosclerosis (MESH:D050197), vascular stiffness (MESH:C566112), hypertension (MESH:D006973), LV hypertrophy (MESH:D017379)
- **Chemicals:** kynurenine (MESH:D007737), BCAAs (MESH:D000597), propionylcarnitine (MESH:C003223), Chloride (MESH:D002712), ketone bodies (MESH:D007657), leucine (MESH:D007930), p-cresyl sulfate (MESH:C408690), lactate (MESH:D019344), Triglycerides (MESH:D014280), docosapentaenoic acid (MESH:C026219), phosphate (MESH:D010710), TMAO (MESH:C005855), sugars (MESH:D000073893), tryptophan (MESH:D014364), creatinine (MESH:D003404), glucose (MESH:D005947), Lipid (MESH:D008055), amino acids (MESH:D000596), HCO3- (MESH:D001639), fatty acid (MESH:D005227), phenylalanine (MESH:D010649), bile acid (MESH:D001647), MRAs (-), Indoxyl sulfate (MESH:D007200), sodium (MESH:D012964), potassium (MESH:D011188)
- **Species:** gut metagenome (species) [taxon 749906], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941167/full.md

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Source: https://tomesphere.com/paper/PMC12941167