Journal of Nephrology

, Volume 29, Issue 6, pp 791–797 | Cite as

Podocyturia is significantly elevated in untreated vs treated Fabry adult patients

  • Hernán TrimarchiEmail author
  • Romina Canzonieri
  • Amalia Schiel
  • Juan Politei
  • Aníbal Stern
  • José Andrews
  • Matías Paulero
  • Tatiana Rengel
  • Alicia Aráoz
  • Mariano Forrester
  • Fernando Lombi
  • Vanesa Pomeranz
  • Romina Iriarte
  • Pablo Young
  • Alexis Muryan
  • Elsa Zotta
Original Article



Proteinuria suggests kidney involvement in Fabry disease. We assessed podocyturia, an early biomarker, in controls and patients with and without enzyme therapy, correlating podocyturia with proteinuria and renal function.


Cross-sectional study (n = 67): controls (Group 1, n = 30) vs. Fabry disease (Group 2, n = 37) subdivided into untreated (2A, n = 19) and treated (2B, n = 18). Variables evaluated: age, gender, creatinine, CKD-EPI, proteinuria, podocyte count/10 20× microscopy power fields, podocytes/100 ml urine, podocytes/g creatininuria (results expressed as median and range).


Group 1 vs. 2 did not differ concerning age, gender and CKD-EPI, but differed regarding proteinuria and podocyturia. Group 2A vs. 2B: age: 29 (18–74) vs. 43 (18–65) years (p = ns); gender: males n = 3 (16 %) vs. n = 9 (50 %). Proteinuria was significantly higher in Fabry treated patients, while CKD-EPI and podocyturia were significantly elevated in untreated individuals. Significant correlations: group 2A: age-proteinuria, ρ = 0.62 (p = 0.0044); age-CKD-EPI, ρ = −0.84 (p < 0.0001); podocyturia-podocytes/100 ml urine, ρ = 0.99 (p = 0.0001); podocyturia-podocytes/g creatininuria ρ = 0.86 (p = 0.0003), podocytes/100 ml urine-podocytes/g urinary creatinine, ρ = 0.84 (p = 0.0004); proteinuria-CKD-EPI, ρ = −0.68 (p = 0.0013). Group 2B: podocyturia-podocytes/100 ml urine, ρ = 0.88 (p < 0.0001); podocyturia-podocytes/g creatininuria, ρ = 0.84 (p < 0.0001); podocytes/100 ml urine-podocytes/g creatininuria, ρ = 0.94 (p < 0.0001); CKD-EPI-proteinuria, ρ = -0.66 (p = 0.0028).


Patients with Fabry disease display heavy podocyturia; those untreated present significantly higher podocyturia, lower proteinuria and better renal function than those who are treated, suggesting that therapy may be started at advanced stages. Podocyturia may antedate proteinuria, and enzyme therapy may protect against podocyte loss.


Fabry disease proteinuria Podocyte Podocyturia Α-galactosidase 



We wish to thank Dr Rosanna Coppo for reviewing our manuscript, and Ms. Laura Ares and Ms. Marina Fernandez for their professional assistance.

Compliance with ethical standards

Conflict of interests

Hernán Trimarchi is a consultant to Genzyme for the product alpha galactosidase-β.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Desnick RJ, Ioannou Y, Eng CM (2001) α-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3733–3774Google Scholar
  2. 2.
    Tondel C, Bostad L, Larsen KK et al (2013) Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol 24:137–148CrossRefPubMedGoogle Scholar
  3. 3.
    Warnock DJ (2005) Fabry disease: diagnosis and management, with emphasis on the renal manifestations. Curr Opin Nephrol Hyperten 14:87–95CrossRefGoogle Scholar
  4. 4.
    Trimarchi H, Forrester M, Lombi F et al (2014) Amiloride as an alternate adjuvant antiproteinuric agent in Fabry disease. The potential roles of plasmin and uPAR. Case Reports in Nephrology 1–6: ID 854521Google Scholar
  5. 5.
    Ortiz A, Oliveira JP, Waldek S et al (2008) Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant 23:1600–1607CrossRefPubMedGoogle Scholar
  6. 6.
    Najafian B, Svarstad E, Bostad L et al (2011) Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int 79:663–670CrossRefPubMedGoogle Scholar
  7. 7.
    Branton MH, Schiffmann R, Sabnis SG et al (2002) Natural history of Fabry renal disease: influence of α-galactosidase A activity and genetic mutations on clinical course. Medicine 81:122–138CrossRefPubMedGoogle Scholar
  8. 8.
    Tsakiris D, Simpson HK, Jones EH et al (1996) Report on management of renal failure in Europe-XXVI, 1995. Rare diseases in renal replacement therapy in the ERA-EDTA Registry. Nephrol Dial Transplant 11:4–20CrossRefPubMedGoogle Scholar
  9. 9.
    Thadhani R, Wolf M, West ML et al (2002) Patients with Fabry disease on dialysis in the United States. Kidney Int 61:249–255CrossRefPubMedGoogle Scholar
  10. 10.
    Nakao S, Kodama C, Takenaka T et al (2003) Fabry disease: detection of undiagnosed hemodialysis patients and identification of a “renal variant” phenotype. Kidney Int 64:801–807CrossRefPubMedGoogle Scholar
  11. 11.
    Kotanko P, Kramar R, Devrnja D et al (2004) Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. J Am Soc Nephrol 15:1323–1329CrossRefPubMedGoogle Scholar
  12. 12.
    Trimarchi H, Canzonieri R, Muryan A, et al (2015) Copious podocyturia without proteinuria and with normal renal function in a young adult with Fabry disease. Case Reports in Nephrology 257628Google Scholar
  13. 13.
    Takahashi N, Yokoi S, Kasuno K (2015) A heterogeneous female with Fabry disease due to a nivel alpha-galactosidase A mutation exhibits a ubnique synaptopodin distributin in vacuolated podocytes. Clin Nephrol 3:301–308CrossRefGoogle Scholar
  14. 14.
    Anasuma K, Kim K, Oh J et al (2005) Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J Clin Invest 115:1188–1198CrossRefGoogle Scholar
  15. 15.
    Ichimura K, Kurihara H, Sakai T (2003) Actin filament organization of foot process in rat podocytes. J Histochem Cytochem 51:1589–1600CrossRefPubMedGoogle Scholar
  16. 16.
    Greka A, Mundel P (2012) Cell biology and pathology of podocytes. Annu Rev Physiol 74:299–323CrossRefPubMedGoogle Scholar
  17. 17.
    Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S et al (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14:931–938CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Smoyer WE, Mundel P, Gupta E et al (1997) Podocyte alpha-actinin induction precedes foot process effacement in experimental nephrotic syndrome. Am J Physiol 273 Renal Physiol 42:F150–F157Google Scholar
  19. 19.
    Vogelmann SU, Nelson WJ, Myers BD et al (2003) Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol 285:F40–F48CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fornoni A, Merscher S, Kopp JB (2014) Lipid biology of podocyte-new perspectives offer new opportunities. Nat Rev Nephrol 10:379–388CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wharram BL, Goyal M, Wiggins JE et al (2005) Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 16:2941–2952CrossRefPubMedGoogle Scholar
  22. 22.
    Trimarchi H (2015) Podocyturia. What is in a name? J Translat Internal Med 3:51–56Google Scholar
  23. 23.
    Jim B, Jean-Louis P, Qipo A et al (2012) Podocyturia as a diagnostic marker of preeclampsia amongst high-risk pregnant patients. J of Pregnancy ID 984630. doi: 10.1155/2012/984630
  24. 24.
    Rodrigues Pereira S, Castro Teixeira V, Nishida SK (2013) Detection of podocyturia in patients with lupus nephritis. J Brasil Nefrol 35:252–258CrossRefGoogle Scholar
  25. 25.
    Maestroni S, Maestroni A, Dell’Antonio G et al (2014) Viable podocyturia in healthy individuals: implications for podocytopathies. Am J Kidney Dis 64:1003–1005CrossRefPubMedGoogle Scholar
  26. 26.
    Mauer M, Glynn E, Svarstad E et al (2014) Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. Plos One 9:e112188CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Germain DP, Charrow J, Desnick RJ et al (2015) Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet 52:353–358CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gaggl M, Hofer M, Weidner S et al (2015) Interfering parameters in the determination of urinary globotriasocylceramide (Gb3) in patients with chronic kidney disease. J Nephrol 6:679–689CrossRefGoogle Scholar
  29. 29.
    Utsumi K, Itoh K, Kase R et al (1999) Urinary excretion of the vitronectin receptor (integrin α V β 3) in patients with Fabry disease. Clin Chimica Acta 279:55–68CrossRefGoogle Scholar
  30. 30.
    Trimarchi H (2015) Plasmin, urokinase plasminogen activator receptor and amiloride in the nephrotic syndrome. In: Nephrotic syndrome. Etiology, pathogenesis and pathology. Mubarak M (ed) Nova Biomedical, New YorkGoogle Scholar
  31. 31.
    Chapman HA, Wei Y (2001) Protease crosstalk with integrins: the urokinase receptor paradigm. Thromb Haemost 86:124–129PubMedGoogle Scholar
  32. 32.
    Wei C, Möller CC, Altintas MM et al (2008) Modification of kidney barrier function by the urokinase receptor. Nat Med 14:55–63CrossRefPubMedGoogle Scholar
  33. 33.
    Regoli M, Bendayan M (1997) Alterations in the expression of the alpha 3 beta 1 integrin in certain membrane domains of the glomerular epithelial cells (podocytes) in diabetes mellitus. Diabetologia 40:15–22CrossRefPubMedGoogle Scholar
  34. 34.
    Sachs N, Sonnenberg A (2013) Cell-matrix adhesion of podocytes in physiology and disease. Nat Rev Nephrol 9:200–210CrossRefPubMedGoogle Scholar
  35. 35.
    Sanchez-Niño MD, Sanz AB, Carrasco S et al (2011) Globotriaosylsphingosine actions on human glomerular podocytes: implications for Fabry nephropathy. Nephrol Dial Transplant 26:1797–1802CrossRefPubMedGoogle Scholar
  36. 36.
    Liebau MC, Braun F, Höpker K et al (2013) Dysregulated autophagy contributes to podocyte damage in Fabry’s disease. PLoS One 8:e63506CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Sanchez-Niño MD, Carpio D, Sanz AB, Ruiz-Ortega M, Mezzano S, Ortiz A (2015) Lyso-GB3 activates Notch 1 in humaan podocytes. Hum Mol Genet 24(20):5720–5734CrossRefPubMedGoogle Scholar
  38. 38.
    Müller-Deile J, Schiffer M (2015) Podocyte directed therapy of nephrotic syndrome-can we bring the inside out? Pediatr Nephrol. doi: 10.1007/s00467-015-3116-4 PubMedGoogle Scholar
  39. 39.
    Mundel P, Gilbert P, Kriz W (1991) Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein. J Histochem Cytochem 39(8):1047–1056CrossRefPubMedGoogle Scholar
  40. 40.
    Nakamura T, Ushiyama C, Suzuki S et al (2000) Urinary excretion of podocytes in patients with diabetic nephropathy. Nephrol Dial Transplant 15:1379–1383CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Nephrology 2016

Authors and Affiliations

  • Hernán Trimarchi
    • 1
    • 6
    Email author
  • Romina Canzonieri
    • 2
  • Amalia Schiel
    • 2
  • Juan Politei
    • 3
  • Aníbal Stern
    • 2
  • José Andrews
    • 1
  • Matías Paulero
    • 1
  • Tatiana Rengel
    • 1
  • Alicia Aráoz
    • 4
  • Mariano Forrester
    • 1
  • Fernando Lombi
    • 1
  • Vanesa Pomeranz
    • 1
  • Romina Iriarte
    • 1
  • Pablo Young
    • 5
  • Alexis Muryan
    • 2
  • Elsa Zotta
    • 4
  1. 1.NephrologyHospital Británico de Buenos AiresBuenos AiresArgentina
  2. 2.Biochemistry ServicesHospital Británico de Buenos AiresBuenos AiresArgentina
  3. 3.Neurology DepartmentFundación para el Estudio de las Enfermedades Metabólicas FESENBuenos AiresArgentina
  4. 4.IFIBIO Houssay, UBA CONICET Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina
  5. 5.Internal MedicineHospital Británico de Buenos AiresBuenos AiresArgentina
  6. 6.Servicio de NefrologíaHospital Británico de Buenos AiresBuenos AiresArgentina

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