Ukr.Biochem.J. 2025; Volume 97, Issue 2, Mar-Apr, pp. 5-12

doi: https://doi.org/10.15407/ubj97.02.005

Podocalyxin and kidney diseases

I. Kostovska

Faculty of Medicine, Ss Cyril and Methodius University in Skopje, North Macedonia;
e-mail: irenakostovska22@yahoo.com

Received: 16 December 2024; Revised: 10 February 2025;
Accepted: 25 April 2025 2025; Available on-line: 12 May 2025

Selectivity of blood filtration by the renal glomerulus is largely determined by the presence in its visceral epithelium of the terminally differentiated “octopus-like” cells called podocytes. Podocalyxin (PODXL) is a major transmembrane glycoprotein located on the podocytes’ apical surface. Recently, the appearance of PODXL in urine has been considered a marker of nephropathy. The purpose of this review article is to analyze the data of studies on the structural and functional features of podocalyxin and its value in diagnostic, prognostic and potential therapeutic relevance in most common kidney diseases.

Keywords: , , , ,


References:

  1. Kopp JB, Anders HJ, Susztak K, Podestà MA, Remuzzi G, Hildebrandt F, Romagnani P. Podocytopathies. Nat Rev Dis Primers. 2020;6(1):68. PubMed, PubMedCentral, CrossRef
  2. Lasagni L, Lazzeri E, Shankland SJ, Anders HJ, Romagnani P. Podocyte mitosis – a catastrophe. Curr Mol Med. 2013;13(1):13-2 PubMed, PubMedCentral, CrossRef
  3. Le Tran N, Wang Y, Nie G. Podocalyxin in Normal Tissue and Epithelial Cancer. Cancers (Basel). 2021;13(12):2863. PubMed, PubMedCentral, CrossRef
  4. McNagny KM, Hughes MR, Graves ML, DeBruin EJ, Snyder K, Cipollone J, Turvey M, Tan PС, McColl S,Roskelley CD. Podocalyxin in the Diagnosis and Treatment of Cancer. In: Advances in Cancer Management. InTech, 2012. CrossRef
  5. Kang HG, Lee M, Lee KB, Hughes M, Kwon BS, Lee S, McNagny KM, Ahn YH, Ko JM, Ha IS, Choi M, Cheong HI. Loss of podocalyxin causes a novel syndromic type of congenital nephrotic syndrome. Exp Mol Med. 2017;49(12):e414. PubMed, PubMedCentral, CrossRef
  6. Zeng L, Fung WW, Chan GC, Ng JK, Chow KM, Szeto CC. Urinary and Kidney Podocalyxin and Podocin Levels in Diabetic Kidney Disease: A Kidney Biopsy Study. Kidney Med. 2022;5(1):100569. PubMed, PubMedCentral, CrossRef
  7. Qiu C, Huang S, Park J, Park Y, Ko YA, Seasock MJ, Bryer JS, Xu XX, Song WC, Palmer M, Hill J, Guarnieri P, Hawkins J, Boustany-Kari CM, Pullen SS, Brown CD, Susztak K. Renal compartment-specific genetic variation analyses identify new pathways in chronic kidney disease. Nat Med. 2018;24(11):1721-1731. PubMed, PubMedCentral, CrossRef
  8. Rosenberg AZ, Kopp JB. Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol. 2017;12(3):502-517. PubMed, PubMedCentral, CrossRef
  9. Müller-Deile J, Schenk H, Schiffer M. Minimal change disease and focal segmental glomerulosclerosis. Internist (Berl). 2019;60(5):450-457. PubMed, CrossRef
  10. Zheng X, Zhong Q, Lin X, Gu X, Ling X, Liang Z, Qin Q, Du X. Transforming growth factor-β1-induced podocyte injury is associated with increased microRNA-155 expression, enhanced inflammatory responses and MAPK pathway activation. Exp Ther Med. 2021;21(6):620. PubMed, PubMedCentral, CrossRef
  11. Refaeli I, Hughes MR, Wong AK, Bissonnette MLZ, Roskelley CD, Wayne Vogl A, Barbour SJ, Freedman BS, McNagny KM. Distinct Functional Requirements for Podocalyxin in Immature and Mature Podocytes Reveal Mechanisms of Human Kidney Disease. Sci Rep. 2020;10(1):9419. PubMed, PubMedCentral, CrossRef
  12. Kravets I, Mallipattu SK. The Role of Podocytes and Podocyte-Associated Biomarkers in Diagnosis and Treatment of Diabetic Kidney Disease. J Endocr Soc. 2020;4(4):bvaa029. PubMed, PubMedCentral, CrossRef
  13. Shelbaya S, Ali HM, Ibrahim RH, Sawirs NS. Podocalyxin as an early marker predicting diabetic nephropathy and its correlation with stages of diabetic nephropathy in type two diabetic patients. QJM An Int J Med. 2021;114(1):hcab100.097. CrossRef
  14. Wang R, Yao C, Liu F. Association between Renal Podocalyxin Expression and Renal Dysfunction in Patients with Diabetic Nephropathy: A Single-Center, Retrospective Case-Control Study. Biomed Res Int. 2020;2020:7350781. PubMed, PubMedCentral, CrossRef
  15. Giannou P, Gakiopoulou H, Stambolliu E, Petras D, Chalkia A, Kapota A, Palamaris K, Hadziyannis E, Thomas K, Alexakou Z, Bora M, Mintzias T, Vassilopoulos D, Patsouris E, Deutsch M. Urine Nephrin and Podocalyxin Reflecting Podocyte Damage and Severity of Kidney Disease in Various Glomerular Diseases-A Cross-Sectional Study. J Clin Med. 2024;13(12):3432.
    PubMed, PubMedCentral, CrossRef
  16. Li JJ, Sa RL, Zhang Y, Yan ZL. Evaluating new biomarkers for diabetic nephropathy: Role of α2-macroglobulin, podocalyxin, α-L-fucosidase, retinol-binding protein-4, and cystatin C. World J Diabetes. 2024;15(6):1212-1225. PubMed, PubMedCentral, CrossRef
  17. Kostovska I, Trajkovska KT, Cekovska S, Topuzovska S, Kavrakova JB, Spasovski G, Kostovski O, Labudovic D. Role of urinary podocalyxin in early diagnosis of diabetic nephropathy. Rom J Intern Med. 2020;58(4):233-241. PubMed, CrossRef
  18.  Wu T, Ding L, Andoh V, Zhang J, Chen L. The Mechanism of Hyperglycemia-Induced Renal Cell Injury in Diabetic Nephropathy Disease: An Update. Life (Basel). 2023;13(2):539. PubMed, PubMedCentral, CrossRef
  19. El-ballat Mostafa Abdel Fattah, Attia Mohamed Hasan, Assem Ahmed Ali Ali, Ellatif Abd Ellatif Ibrahim Abd. Role of Urinary Podocalyxin In Early Diagnosis of Diabetic Kidney Disease. Al-Azhar Int Med J. 2023;4(12):55. CrossRef
  20. Khaled Mahfouz Abdel Naim Ibrahim, Yasser Suleiman Ahmed, Manal Ibrahim Mohammed Salman, Walid Ahmed Bashary, Hussein Sayed Hussein. Urinary Podocalyxin Is an Early Marker for Podocyte Injury in Patients with Diabetic Nephropathy as well as Other Glomerular Disease. QJM Int J Med. 2023;116(Suppl 1):hcad069.437. CrossRef
  21. Xie Y, Jin D, Qiu H, Lin L, Sun S, Li D, Sha F, Zhou W, Jia M. Assessment of urinary podocalyxin as an alternative marker for urinary albumin creatinine ratio in early stage of diabetic kidney disease in older patients. Nefrologia (Engl Ed). 2022;42(6):664-670. PubMed, CrossRef
  22. Panek-Laszczyńska K, Konieczny A, Milewska E, Dąbrowska K, Bąchor R, Witkiewicz W, Szewczuk Z. Podocyturia as an early diagnostic marker of preeclampsia: a literature review. Biomarkers. 2018;23(3):207-212. PubMed, CrossRef
  23. Kerley RN, McCarthy C. Biomarkers of glomerular dysfunction in pre-eclampsia – A systematic review. Pregnancy Hypertens. 2018;14:265-272. PubMed, CrossRef
  24. Mansilla M, Wang Y, Hyett J, da Silva Costa F, Nie G Serum podocalyxin for early detection of preeclampsia at 11-13 weeks of gestation. Placenta. 2018;71:13-15. PubMed, CrossRef
  25. Kostovska I, Tosheska Trajkovska K, Kostovski O, Labudovic D. Urinary Nephrin and Podocalyxin Levels as Predictors of Pre-eclampsia in High-Risk Pregnant Women. Folia Med (Plovdiv). 2021;63(6):948-957. PubMed, CrossRef
  26. Uzun ND, Sarııbrahım Astepe B, Uzun F, Kale E. Predictive value of maternal serum podocalyxin in the diagnosis of preeclampsia: a prospective case-control study. Ginekol Pol. 2021;93(3):229-234. PubMed, CrossRef
  27. Nikolov AG, Popovski NK, Blazheva S. Levels of serum podocalyxin in preeclampsia and relationship with maternal echocardiographic and Doppler ultrasound parameters. Folia Med (Plovdiv). 2022;64(6):913-921. PubMed, CrossRef
  28. Fukuda A, Sato Y, Shibata H, Fujimoto S, Wiggins RC. Urinary podocyte markers of disease activity, therapeutic efficacy, and long-term outcomes in acute and chronic kidney diseases. Clin Exp Nephrol. 2024;28(6):496-504. PubMed, PubMedCentral, CrossRef
  29. Fogo A, Breyer JA, Smith MC, Cleveland WH, Agodoa L, Kirk KA, Glassock R. Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: a report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators. Kidney Int. 1997;51(1):244-252. PubMed, CrossRef
  30. Wang G, Lai FM, Kwan BC, Lai KB, Chow KM, Li PK, Szeto CC. Podocyte loss in human hypertensive nephrosclerosis. Am J Hypertens. 2009;22(3):300-306. PubMed, CrossRef
  31. Guo Z, Guo Q, Li X, Gao X, Zhang L, Xu K. Urinary biomarkers associated with podocyte injury in lupus nephritis. Front Pharmacol. 2024;15:1324540. PubMed, PubMedCentral, CrossRef
  32. Abou Ghanima AT, Almaghraby MF, Elsaadany HM, Hosny MA, Kumar RK. Urinary podocalyxin and nephrin levels as biomarkers in lupus nephritis patients: Relation to renal involvement and disease activity. Egyptian Rheumatologist. 2016;38(3):177-182. CrossRef

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