{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:56:03Z","timestamp":1790916963241,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with chronic kidney disease (CKD) presenting as nephrotic-range proteinuria (NR, \u22653.5g\/d) exhibit distinct clinical phenotypes with and without hypoalbuminemia. The underlying mechanisms need further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included patients with CKD hospitalized over the past two years with baseline 24-hour urine total protein (24-hUTP) exceeding 3.5g. Based on whether their baseline serum albumin (ALB) levels were \u226430 g\/L, patients were assigned to two groups: the nephrotic syndrome (NS) group and the isolated nephropathy-range proteinuria (isolated NR) group. Clinical indicators and urine tubular injury biomarkers were compared between the two groups. The Spearman correlation coefficient was used to analyze the association between clinical indicators and urinary biomarker profiles. Urinary biomarkers and the isolated NR phenotype were evaluated for their independent association using multivariate logistic regression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In all, 134 patients were divided into 83 isolated NR and 51 NS groups. Urinary transferrin (uTRF) and N-acetyl-\u03b2-D-glucosaminidase (uNAG) were higher in the NS group than in the isolated NR group. The isolated NR group, in contrast, had significant high level of urinary retinol-binding protein (uRBP). Additionally, the two groups\u2019 uRBP exhibited distinct correlation patterns with proteinuria. Multivariate logistic regression study demonstrated that uRBP and uTRF were independently linked to the phenotypes after controlling for relevant variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with NR with and without hypoalbuminemia exhibited distinct urinary biomarker profiles. Higher uRBP levels in patients without hypoalbuminemia may indicate differences in proximal tubular handling of low-molecular-weight proteins. In contrast, higher uTRF and uNAG levels in patients with hypoalbuminemia may reflect greater glomerular permeability abnormalities accompanied by tubular cellular injury. These findings are hypothesis-generating, and the potential involvement of megalin-mediated protein handling requires direct experimental and histopathological validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1938326","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:38:32Z","timestamp":1790915912000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differences in urinary biomarker profiles in patients with nephrotic-range proteinuria with and without hypoalbuminemia: a single-center cross-sectional study"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingnan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hohhot Hospital of Traditional Chinese Medicine and Mongolian Medicine","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990\u20132023, and its attributable risk factors: a systematic analysis for the global burden of disease study 2023","volume":"406","author":"Mark","year":"2025","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1053\/j.ajkd.2014.02.020","article-title":"Early change in proteinuria as a surrogate endpoint for kidney disease progression: an individual patient meta-analysis","volume":"64","author":"Inker","year":"2014","journal-title":"Am J Kidney Diseases: Off J Natl Kidney Foundation"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.09741110","article-title":"Associations among estimated glomerular filtration rate, proteinuria, and adverse cardiovascular outcomes","volume":"6","author":"Bello","year":"2011","journal-title":"Clin J Am Soc Nephrology: CJASN"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.292","article-title":"The increased risk of coronary heart disease associated with nephrotic syndrome","volume":"44","author":"Ordo\u00f1ez","year":"1993","journal-title":"Kidney Int"},{"key":"B5","doi-asserted-by":"publisher","first-page":"101240","DOI":"10.1016\/j.eclinm.2021.101240","article-title":"Nephrotic-range proteinuria in type 2 diabetes: effects of empagliflozin on kidney disease progression and clinical outcomes","volume":"43","author":"Ruggenenti","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2267138","DOI":"10.1080\/0886022X.2023.2267138","article-title":"Clinical significance of massive proteinuria in primary IgA nephropathy with and without nephrotic syndrome: a single center cohort study","volume":"45","author":"Hu","year":"2023","journal-title":"Renal Failure"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.02.1030","article-title":"Serum albumin at partial remission predicts outcomes in membranous nephropathy","volume":"5","author":"Lee","year":"2020","journal-title":"Kidney Int Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00840.x","article-title":"Pathophysiology of proteinuria","volume":"63","author":"D\u2019Amico","year":"2003","journal-title":"Kidney Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs462","article-title":"Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration","volume":"28","author":"Storm","year":"2013","journal-title":"Nephrology Dialysis Transplantation: Off Publ Eur Dialysis Transplant Assoc - Eur Renal Assoc"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1159\/000054730","article-title":"Urinary retinol-binding protein as a prognostic marker in glomerulopathies","volume":"90","author":"Kirsztajn","year":"2002","journal-title":"Nephron"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101433","article-title":"Electrochemical N-acetyl-\u03b2-D-glucosaminidase urinalysis: toward sensor chip-based diagnostics of kidney malfunction","volume":"11","author":"Vibulcharoenkitja","year":"2021","journal-title":"Biomolecules"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.03.026","article-title":"The promise of tubule biomarkers in kidney disease: a review","volume":"78","author":"Ix","year":"2021","journal-title":"Am J Kidney Diseases: Off J Natl Kidney Foundation"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-S011","article-title":"11. Chronic kidney disease and risk management: standards of care in diabetes-2023","volume":"46","author":"ElSayed","year":"2023","journal-title":"Diabetes Care"},{"key":"B15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/978-981-13-8871-2_24","article-title":"New understanding on the role of proteinuria in progression of chronic kidney disease","volume":"1165","author":"Liu","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00907-0","article-title":"Crosstalk between glomeruli and tubules","volume":"21","author":"Fogo","year":"2025","journal-title":"Nat Rev Nephrol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad215","article-title":"Tubular toxicity of proteinuria and the progression of chronic kidney disease","volume":"39","author":"Makhammajanov","year":"2024","journal-title":"Nephrology Dialysis Transplantation: Off Publ Eur Dialysis Transplant Assoc - Eur Renal Assoc"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fneph.2024.1469388","article-title":"Proteinuria and proximal tubular epithelial cells: correlation between immunofluorescence, histology, and degree of proteinuria","volume":"4","author":"Chow","year":"2024","journal-title":"Front Nephrol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/146987","article-title":"Urinary markers of glomerular injury in diabetic nephropathy","volume":"2012","author":"Cohen-Bucay","year":"2012","journal-title":"Int J Nephrol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering10040444","article-title":"Revisiting the role of NAG across the continuum of kidney disease","volume":"10","author":"Novak","year":"2023","journal-title":"Bioengineering"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00022.2012","article-title":"Endocytic receptors in the renal proximal tubule","volume":"27","author":"Christensen","year":"2012","journal-title":"Physiology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013090950","article-title":"The proximal tubule and albuminuria: really","volume":"25","author":"Dickson","year":"2014","journal-title":"J Am Soc Nephrology: JASN"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104537","article-title":"Megalin: a bridge connecting kidney, the renin-angiotensin system, and atherosclerosis","volume":"151","author":"Kukida","year":"2020","journal-title":"Pharmacol Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-025-06745-x","article-title":"Tubular proteinuria due to hereditary endocytic receptor disorder of the proximal tubule: dent disease and chronic benign proteinuria","volume":"40","author":"Sakakibara","year":"2025","journal-title":"Pediatr Nephrol (Berlin Germany)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00378.2013","article-title":"Megalin in acute kidney injury: foe and friend","volume":"306","author":"Mahadevappa","year":"2014","journal-title":"Am J Physiol Renal Physiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.02.012","article-title":"Proximal tubular expression patterns of megalin and cubilin in proteinuric nephropathies","volume":"2","author":"Sun","year":"2017","journal-title":"Kidney Int Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1113\/jp286245","article-title":"Renal handling of albumin in rats with early stage diabetes: a theoretical analysis","volume":"602","author":"Edwards","year":"2024","journal-title":"J Physiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13335","article-title":"Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR","volume":"5","author":"Figueira","year":"2017","journal-title":"Physiol Rep"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1238927","article-title":"Tubular injury in diabetic kidney disease: molecular mechanisms and potential therapeutic perspectives","volume":"14","author":"Wang","year":"2023","journal-title":"Front Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1938326\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:38:44Z","timestamp":1790915924000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1938326\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":29,"alternative-id":["10.3389\/fendo.2026.1938326"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1938326","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"article-number":"1938326"}}