{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:28:02Z","timestamp":1786116482937,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cGrigore T. Popa\u201d University of Medicine and Pharmacy Iasi, Romania","award":["10063\/15 May 2025"],"award-info":[{"award-number":["10063\/15 May 2025"]}]},{"award":["10063\/15 May 2025"],"award-info":[{"award-number":["10063\/15 May 2025"]}],"id":[{"id":"https:\/\/ror.org\/03hd30t45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Chronic kidney disease (CKD) is characterized by persistent inflammation, metabolic dysregulation, and mineral and bone disorder (CKD-MBD), all of which may affect ocular tissues. While retinal manifestations of CKD have been increasingly investigated, data regarding clinical anterior segment modifications and their relationship with systemic biochemical parameters remain limited. Methods: We performed a cross-sectional study including 130 participants: 53 non-CKD subjects, 29 patients undergoing maintenance hemodialysis (HD), and 48 kidney transplant recipients (KTRs). All participants underwent comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement using Goldmann applanation tonometry, Schirmer I test, tear break-up time (TBUT) and assessment of cataract and blepharitis prevalence. Serum creatinine estimated glomerular filtration rate (eGFR), calcium, phosphate, parathyroid hormone (PTH), magnesium, 25-hydroxyvitamin D, and Activin A were recorded. Associations between ocular and systemic parameters were evaluated using correlation and regression analyses. Results: TBUT, Schirmer I and IOP did not differ significantly among groups (all p &gt; 0.05). After adjustment for age, sex, BMI and diabetes mellitus (DM), HD patients showed worse visual acuity than the non-CKD reference group, reflected by higher logMAR BCVA values (adjusted B = +0.128, p = 0.024). In KTRs, higher corrected calcium was independently associated with reduced tear film parameters, correlating with both shorter TBUT (B = \u22120.903, p = 0.037) and lower Schirmer I values (B = \u22125.947, p = 0.008). Circulating Activin A increased progressively from controls to KTR to HD patients (median 189.5 vs. 273.0 vs. 314.0 pg\/mL, p &lt; 0.001) but showed no independent association with any anterior segment parameter; it was instead associated with cumulative glucocorticoid exposure (B = +1.602, p = 0.024). Conclusions: In CKD, clinical anterior segment and ocular surface differences were largely explained by age, sex, and comorbidity rather than renal replacement modality, with visual acuity deficit persisting in HD after adjusting for these covariates. At the individual level, corrected calcium was the parameter most consistently associated with tear film parameters in KTRs, whereas elevated Activin A was not independently associated with ocular involvement and likely reflects systemic disease activity.<\/jats:p>","DOI":"10.3390\/life16081294","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:46:38Z","timestamp":1786009598000},"page":"1294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Anterior Segment and Ocular Surface Findings Across Renal Replacement Modalities: Associations with CKD-Related Factors, Mineral Metabolism and Activin A"],"prefix":"10.3390","volume":"16","author":[{"given":"Ioana-Madalina","family":"Bilha","sequence":"first","affiliation":[{"name":"Department of Morpho-Functional Sciences I-Histology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-8558","authenticated-orcid":false,"given":"Stefana Catalina","family":"Bilha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Endocrinology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Akad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Nephrology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9985-2486","authenticated-orcid":false,"given":"Adrian","family":"Covic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Nephrology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Hoga\u0219","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Nephrology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai Marian","family":"Hoga\u0219","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences II, Discipline of Physiology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana Alina","family":"Halip","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III-Dermatology-Venerology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-9262","authenticated-orcid":false,"given":"Calina Anda","family":"Sandu-Boz","sequence":"additional","affiliation":[{"name":"Department of Surgery II-Ophthalmology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-7714","authenticated-orcid":false,"given":"Camelia Margareta","family":"Bogdanici","sequence":"additional","affiliation":[{"name":"Department of Surgery II-Ophthalmology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina Draga","family":"Caruntu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I-Histology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Romanian Medical Science Academy, 030171 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7775","DOI":"10.1038\/s41467-023-43125-1","article-title":"Choroidal and Retinal Thinning in Chronic Kidney Disease Independently Associate with eGFR Decline and Are Modifiable with Treatment","volume":"14","author":"Farrah","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e89173","DOI":"10.1172\/jci.insight.89173","article-title":"Chorioretinal Thinning in Chronic Kidney Disease Links to Inflammation and Endothelial Dysfunction","volume":"1","author":"Balmforth","year":"2016","journal-title":"JCI Insight"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Basiony, A.I., Atta, S.N., Dewidar, N.M., and Zaky, A.G. (2023). Association of Chorioretinal Thickness with Chronic Kidney Disease. BMC Ophthalmol., 23.","DOI":"10.1186\/s12886-023-02802-x"},{"key":"ref_4","first-page":"553","article-title":"Association of Chronic Kidney Disease and Retinal Changes Measured by Optical Coherence Tomography: A Systematic Review and Meta-Analysis","volume":"65","author":"Bineshfar","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Roskal-Wa\u0142ek, J., Go\u0142\u0119biewska, J., Mackiewicz, J., Wa\u0142ek, P., Bociek, A., Biskup, M., Odrobina, D., and Jaroszy\u0144ski, A. (2023). The Haemodialysis Session Effect on the Choroidal Thickness and Retinal and Choroidal Microcirculation\u2014A Literature Review. J. Clin. Med., 12.","DOI":"10.3390\/jcm12247729"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4103\/tjo.tjo_24_20","article-title":"Corneal Biomechanical Properties in Patients with Kidney Transplant","volume":"11","author":"Jain","year":"2021","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"176","DOI":"10.5935\/0004-2749.20170043","article-title":"Effects of Hemodialysis on Corneal and Anterior Chamber Morphometry and Intraocular Pressure in Patients with End-Stage Renal Disease","volume":"80","author":"Caglayan","year":"2017","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.2147\/OPTH.S335989","article-title":"The Relationship Between Dry Eye in Adults with Indications for Kidney Transplantation and Influencing Factors","volume":"15","author":"Thang","year":"2021","journal-title":"Clin. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S123","DOI":"10.1016\/j.ekir.2024.11.283","article-title":"WCN25-4324: Pattern of Tear Film Production Among Patients with Chronic Kidney Disease in Nigeria: Emerging Trends","volume":"10","author":"Chimezie","year":"2025","journal-title":"Kidney Int. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1440-1797.2007.00805.x","article-title":"Alterations in Ocular Surface and Corneal Thickness in Relation to Metabolic Control in Patients with Chronic Renal Failure","volume":"12","author":"Ozdek","year":"2007","journal-title":"Nephrology"},{"key":"ref_11","first-page":"186","article-title":"Ocular Surface Findings in Chronic Renal Failure","volume":"11","author":"Temiz","year":"2014","journal-title":"Electron. J. Gen. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II Pathophysiology Report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/ndt\/gfaa203","article-title":"The Role of Activin: The Other Side of Chronic Kidney Disease\u2013Mineral Bone Disorder?","volume":"36","author":"Cianciolo","year":"2021","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1093\/ckj\/sfad238","article-title":"Plasma Activin A Rises with Declining Kidney Function and Is Independently Associated with Mortality in Patients with Chronic Kidney Disease","volume":"16","author":"Nordholm","year":"2023","journal-title":"Clin. Kidney J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"B\u00eelha, I.M., B\u00eelha, \u0218.C., Akad, N., Covic, A., Br\u0103ni\u0219teanu, D.C., Hoga\u0219, S., Hoga\u0219, M.M., Matei, A., Ungureanu, M.C., and Sandu-Boz, C.A. (2026). Retinal Structural and Microvascular Findings on OCT and OCTA in Hemodialysis and Kidney Transplant Recipients and Their Association with Mineral Metabolism Parameters. Med. Sci., 14.","DOI":"10.3390\/medsci14030381"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2455251","DOI":"10.1001\/jamanetworkopen.2024.55251","article-title":"Use of Albumin-Adjusted Calcium Measurements in Clinical Practice","volume":"8","author":"King","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A New Equation to Estimate Glomerular Filtration Rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1159\/000475555","article-title":"Association Between Chronic Kidney Disease and Risk of Cataract: A Nationwide Retrospective Cohort Study","volume":"45","author":"Liu","year":"2017","journal-title":"Am. J. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Huang, C.Y., Lee, J.I., Chang, C.W., Liu, Y.H., Huang, S.P., Chen, S.C., and Geng, J.H. (2022). Chronic Kidney Disease and Its Association with Cataracts\u2014A Cross-Sectional and Longitudinal Study. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.1029962"},{"key":"ref_20","first-page":"20","article-title":"Ocular Manifestations in Hemodialysis Patients: Importance of Ophthalmic Examination in Prevention of Ocular Sequelae","volume":"10","author":"Moghadam","year":"2019","journal-title":"Int. J. Prev. Med."},{"key":"ref_21","first-page":"1142","article-title":"Changes of Serum Calcium, Phosphorus, and Parathyroid Hormone Concentrations and Ocular Findings Among Patients Undergoing Hemodialysis","volume":"22","author":"Pakdel","year":"2011","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_22","first-page":"457","article-title":"Impact of Hemodialysis on Visual Parameters in Patients with End-Stage Renal Disease","volume":"6","author":"Ghasemi","year":"2012","journal-title":"Iran. J. Kidney Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Asiedu, K., Alotaibi, S., Krishnan, A.V., and Downie, L.E. (2023). Chronic Kidney Disease Has No Impact on Tear Film Substance P Concentration in Type 2 Diabetes. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092368"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1167\/iovs.09-4573","article-title":"Mechanism for Carbachol-Induced Secretion of Lacritin in Cultured Monkey Lacrimal Acinar Cells","volume":"51","author":"Walkup","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jtos.2019.01.007","article-title":"Expression of BK Channels and Na+\/K+ Pumps in the Apical Membrane of Lacrimal Acinar Cells Suggests a New Molecular Mechanism for Primary Tear Secretion","volume":"17","author":"Skaliczki","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/01.ASN.0000103225.68136.E6","article-title":"Activin A Is a Potent Activator of Renal Interstitial Fibroblasts","volume":"15","author":"Yamashita","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sugatani, T. (2018). Systemic Activation of Activin A Signaling Causes Chronic Kidney Disease\u2013Mineral Bone Disorder. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092490"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"376191","DOI":"10.1155\/2014\/376191","article-title":"Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction","volume":"2014","author":"Maeshima","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s11658-023-00424-1","article-title":"A Therapeutic Target for CKD: Activin A Facilitates TGF\u03b21 Profibrotic Signaling","volume":"28","author":"Soomro","year":"2023","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.bone.2017.01.023","article-title":"The Chronic Kidney Disease\u2013Mineral Bone Disorder (CKD-MBD): Advances in Pathophysiology","volume":"100","author":"Hruska","year":"2017","journal-title":"Bone"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1294\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T10:04:14Z","timestamp":1786010654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["life16081294"],"URL":"https:\/\/doi.org\/10.3390\/life16081294","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}