{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:15Z","timestamp":1787027775874,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart\/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p &lt; 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p &lt; 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p &lt; 0.05), and between RRI and suPAR (r = 0.331, p &lt; 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients.<\/jats:p>","DOI":"10.3390\/biom15091297","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T12:15:17Z","timestamp":1757420117000},"page":"1297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Cardiorenal Involvement in Systemic Sclerosis Patients"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-4846","authenticated-orcid":false,"given":"Chiara","family":"Pellicano","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"D\u2019Ippolito","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavio","family":"Martellucci","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-2570","authenticated-orcid":false,"given":"Umberto","family":"Basile","sequence":"additional","affiliation":[{"name":"Dipartimento di Patologia Clinica, Ospedale Santa Maria Goretti, A.U.S.L. Latina, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Carnazzo","sequence":"additional","affiliation":[{"name":"Dipartimento di Patologia Clinica, Ospedale Santa Maria Goretti, A.U.S.L. Latina, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-070X","authenticated-orcid":false,"given":"Valerio","family":"Basile","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Cancer Biobank, Department of Research and Advanced Technologies, I.R.C.C.S. Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-8093","authenticated-orcid":false,"given":"Edoardo","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-6378","authenticated-orcid":false,"given":"Mariapaola","family":"Marino","sequence":"additional","affiliation":[{"name":"Sezione di Patologia Generale, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Sezione di Patologia Generale, Dipartimento di Medicina e Chirurgia Traslazionale, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d I.R.C.C.S., 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2015-765X","authenticated-orcid":false,"given":"Antonietta","family":"Gigante","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","first-page":"29","article-title":"EULAR recommendations for the treatment of systemic sclerosis: 2023 update","volume":"84","author":"Lescoat","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e840","DOI":"10.1161\/CIR.0000000000000664","article-title":"American Heart Association Council on the Kidney in Cardiovascular Disease and Council on Clinical Cardiology. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association","volume":"139","author":"Rangaswami","year":"2019","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.33549\/physiolres.935110","article-title":"Cardiorenal Syndromes and Their Role in Water and Sodium Homeostasis","volume":"73","author":"Salajova","year":"2024","journal-title":"Physiol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2165\/00003495-199000394-00004","article-title":"Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function","volume":"39","author":"Ljungman","year":"1990","journal-title":"Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhang, X., Fishlock, S., Sharpe, P., and McLaughlin, J. (2022, January 11\u201315). Cystatin C as a biomarker for cardiorenal syndrome diseases quantitative diagnostics and monitoring via point-of-care. Proceedings of the 2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Glasgow, Scotland, UK.","DOI":"10.1109\/EMBC48229.2022.9871131"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jacc.2004.09.061","article-title":"Cystatin-C and mortality in elderly persons with heart failure","volume":"45","author":"Shlipak","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejim.2025.03.008","article-title":"Accuracy of glomerular filtration rate estimating equations in systemic sclerosis","volume":"138","author":"Pellicano","year":"2025","journal-title":"Eur. J. Intern. Med."},{"key":"ref_8","first-page":"2789410","article-title":"Value of Plasma NGAL and Creatinine on First Day of Admission in the Diagnosis of Cardiorenal Syndrome Type 1","volume":"2020","author":"Thai","year":"2020","journal-title":"Cardiol. Res. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2217\/bmm-2018-0349","article-title":"Association Between High Gal-3 Serum Levels and Worsening of Renal Function in Chronic Heart Failure Outpatients","volume":"13","author":"Iacoviello","year":"2019","journal-title":"Biomark. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e015452","DOI":"10.1161\/JAHA.119.015452","article-title":"Cardio-Renal Biomarker Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated With Cardiovascular Death and Myocardial Infarction in Patients With Coronary Artery Disease Independent of Troponin, C-Reactive Protein, and Renal Function","volume":"9","author":"Nikorowitsch","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","article-title":"2013 classification criteria for systemic sclerosis: An American college of rheumatology\/European league against rheumatism collaborative initiative","volume":"72","author":"Khanna","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","first-page":"202","article-title":"Scleroderma (systemic sclerosis): Classification, subsets and pathogenesis","volume":"15","author":"Leroy","year":"1988","journal-title":"J. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/annrheumdis-2016-209768","article-title":"The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: Derivation and validation of a preliminarily revised EUSTAR activity index","volume":"76","author":"Valentini","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","first-page":"2159","article-title":"A disease severity scale for systemic sclerosis: Development and testing","volume":"26","author":"Medsger","year":"1999","journal-title":"J. Rheumatol."},{"key":"ref_15","first-page":"663","article-title":"Nailfold capillaroscopy and classification criteria for systemic sclerosis","volume":"25","author":"Cutolo","year":"2007","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.semarthrit.2011.11.005","article-title":"Intrarenal Hemodynamic Parameters Correlate with Glomerular Filtration Rate and Digital Microvascular Damage in Patients with Systemic Sclerosis","volume":"41","author":"Rosato","year":"2012","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/eurheartj\/ehp507","article-title":"Cardio-renal syndromes: Report from the consensus conference of the Acute Dialysis Quality Initiative","volume":"31","author":"Ronco","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1093\/rheumatology\/keab748","article-title":"In systemic sclerosis, the TAPSE\/sPAP ratio can be used in addition to the DETECT algorithm for pulmonary arterial hypertension diagnosis","volume":"61","author":"Colalillo","year":"2021","journal-title":"Rheumatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103330","DOI":"10.1016\/j.autrev.2023.103330","article-title":"Renal involvement in systemic sclerosis","volume":"22","author":"Scheen","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejim.2019.09.001","article-title":"The Renal Resistive Index in systemic sclerosis: Determinants, prognostic implication and proposal for specific age-adjusted cut-offs","volume":"70","author":"Bruni","year":"2019","journal-title":"Eur. J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/art.1780310311","article-title":"Renal vascular histology and morphometry in systemic sclerosis. a case\u2013control autopsy study","volume":"31","author":"Trostle","year":"1988","journal-title":"Arthritis Rheum."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10238-024-01374-4","article-title":"Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients","volume":"24","author":"Pellicano","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/ndt\/gfs380","article-title":"Urinary and serum biomarkers for the diagnosis of acute kidney injury: An in-depth review of the literature","volume":"28","author":"Vanmassenhove","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.amjms.2022.02.014","article-title":"Assessment of kidney involvement in systemic sclerosis: From scleroderma renal crisis to subclinical renal vasculopathy","volume":"364","author":"Gigante","year":"2022","journal-title":"Am. J. Med Sci."},{"key":"ref_25","first-page":"76","article-title":"Comparative Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C as Early Biomarkers for Early Detection of Renal Failure in Patients with Hypertension","volume":"19","author":"Gharishvandi","year":"2015","journal-title":"Iran. Biomed. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"476","DOI":"10.2215\/CJN.06140710","article-title":"Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis of Type 1 Cardio-Renal Syndrome in the General Ward","volume":"6","author":"Alvelos","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_27","first-page":"67","article-title":"Early diagnosis of acute renal injury in patients with acute decompensation of chronic heart failure","volume":"91","author":"Nasonova","year":"2019","journal-title":"Ter. Arkhiv"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1159\/000440775","article-title":"The Role of Congestion in Cardiorenal Syndrome Type 2: New Pathophysiological Insights into an Experimental Model of Heart Failure","volume":"6","author":"Angelini","year":"2015","journal-title":"Cardiorenal Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rasmussen, L.J.H., Petersen, J.E.V., and Eugen-Olsen, J. (2021). Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.780641"},{"key":"ref_30","first-page":"122","article-title":"The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders","volume":"27","author":"Vasarhelyi","year":"2016","journal-title":"Electron. J. IFCC"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/ki.2014.346","article-title":"A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease","volume":"87","author":"Spinale","year":"2015","journal-title":"Kidney Int."},{"key":"ref_32","first-page":"599","article-title":"Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review)","volume":"41","author":"Dong","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ijcard.2016.12.140","article-title":"Galectin-3 is an independent predictor of survival in systemic sclerosis","volume":"233","author":"Faludi","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1136\/ard.55.7.455","article-title":"Diastolic abnormalities in systemic sclerosis: Evidence for associated defective cardiac functional reserve","volume":"55","author":"Valentini","year":"1996","journal-title":"Ann. Rheum. Dis."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/9\/1297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:42:36Z","timestamp":1760035356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/9\/1297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":34,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biom15091297"],"URL":"https:\/\/doi.org\/10.3390\/biom15091297","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]}}}