Podocyturia: What is in a name?


The podocyte is a highly differentiated cell located in the outer space of the glomerular basement membrane that deals with many different functions. This phylogenetically preserved cell that is responsible for the virtually absence of proteins in the urine lacks of the capacity to divide under normal conditions. When podocytes receive molecular insults, which normally occur during stress conditions as glomerulonephritis, hyperfiltration or metabolic disturbances, they adapt to the new situation by contracting their actin fibers. This adaptive behavior puts at risk the quality of the plasmatic filtration due to the denudation of the glomerular basement membrane, the potential mesangial inflammation and the appearance of proteinuria; podocytes run the risk of detachment from the basement membrane due to a decrease in the adherence to the surrounding matrix after contraction, a process called foot processes effacement. Podocytes change their shape and under constant mechanical stress they finally detach, rendering the glomerular basement membrane unprotected unless other contiguous podocytes are capable of covering the surface. However, these still anchored podocytes are generally also under the same stress situation and follow the same pathway. Podocyturia refers to the presence of these differentiated cells in the urinary sediment. Noteworthy, the podocytes that are encountered in the urine are viable despite the glomerular hostile environment and the urinary acidity. Podocyturia can precede proteinuria and can aggravate it. Therefore, in diseases that can threaten the glomerular normal environment, the presence and the quantification of urinary podocytes can be of remarkable relevance, as it can herald or accompany the appearance of proteinuria, and could offer another view to the interpretation and clinical approach and outcome of proteinuria. However, its identification needs a wide-spread training among biochemists and technicians, as well as commercially available kits.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Jefferson JA, Alpers CE, Shankland SJ. Podocyte Biology for the Bedside. Am J Kidney Dis 2011;58:835-45.

  • 2. Jefferson JA, Nelson PJ, Najafian B, Shankland SJ. Podocyte Disorders: Core Curriculum 2011. Am J Kidney Dis 2011;58:666-77.

  • 3. Haraldsson B, Jeansson M. Glomerular filtration barrier. Curr Opin Nephrol Hypertens 2009;18:331-5.

  • 4. Patrakka J, Tryggvason K. New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 2009;5:463-8.

  • 5. Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 2003;111:707-16.

  • 6. Banas MC, Banas B, Hudkins KL, Wietecha TA, Iyoda M, Bock E, et al. TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 2008;19:704-13.

  • 7. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 2004;113:1390-7.

  • 8. Trimarchi H. Abatacept in glomerular diseases. The open road for the second signal as a new target is settled down. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 2015;9:1-13.

  • 9. Luyckx VA, Brenner BM. The clinical importance of nephron mass. J Am Soc Nephrol 2010;21:898-910.

  • 10. Tan JC, Workeneh B, Busque S, Blouch K, Derby G, Myers BD. Glomerular function, structure, and number in renal allografts from older deceased donors. J Am Soc Nephrol 2009;20:181-8.

  • 11. Romagnani P, Lasagni L, Remuzzi G. Renal progenitors: An evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol 2013;9:137-46.

  • 12. Vogelmann SU, Nelson WJ, Myers BD, Lemley KV. Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol 2003;285:F40-8.

  • 13. Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, et al. Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol 2006;17:2443-56.

  • 14. Mazzinghi B, Ronconi E, Lazzeri E, Sagrinati C, Ballerini L, Angelotti ML, et al. Essential but differential role for CXCR4 and CXCR7 in the therapeutic homing of human renal progenitor cells. J Exp Med 2008;205:479-90.

  • 15. Ronconi, E, Sagrinati C, Angelotti ML, Lazzeri E, Mazzinghi B, Ballerini L, et al. Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol 2009;20:322-32.

  • 16. Lazzeri E, Crescioli C, Ronconi E, Mazzinghi B, Sagrinati C, Netti GS, et al. Regenerative potential of embryonic renal multipotent progenitors in acute renal failure. J Am Soc Nephrol 2007;18:3128-38.

  • 17. Angelotti ML, Ronconi E, Ballerini L, Peired A, Mazzinghi B, Sagrinati C, et al. Characterization of renal progenitors committed toward the tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 2012;30:1714-25.

  • 18. Sallustio F, De Benedictis L, Castellano G, Zaza G, Loverre A, Costantino V, et al. TLR2 plays a role in the activation of human resident renal stem/progenitor cells. FASEB J 2010;24:514-25.

  • 19. Kriz W, Shirato I, Nagata M, LeHir M, Lemley KV. The podocyte’s response to stress: The enigma of foot process effacement. Am J Physiol Renal Physiol 2013;304:F333-47.

  • 20. Couser WG. Basic and translational concepts of immune-mediated glomerular diseases J Am Soc Nephrol 2012;23:381-99.

  • 21. Trimarchi H. Primary focal and segmental glomerulosclerosis and suPAR: Where do we stand and where are we heading to?. World J Nephrol 2013;2:103-22.

  • 22. Wei C, Moller CC, Altintas MM, Li J, Schwarz K, Zacchigna S, et al. Modification of kidney barrier function by the urokinase receptor. Nat Med 2008;14:55-63.

  • 23. Jefferson JA, Shankland SJ, Pichler RH. Proteinuria in diabetic kidney disease: A mechanistic viewpoint. Kidney Int 2008;74:22-36.

  • 24. Shankland SJ. The podocyte’s response to injury: Role in proteinuria and glomerulosclerosis. Kidney Int 2006;69:2131-47.

  • 25. Wharram BL, Goyal M, Wiggins JE, Sanden SK, Hussain S, Filipiak WE, et al. Podocyte depletion causes glomerulosclerosis: Diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 2005;16:2941-52.

  • 26. Peti-Peterdi J, Sipos A. A high-powered view of the filtration barrier. J Am Soc Nephrol 2010;21:1835-41.

  • 27. Becker JU, Hoerning A, Schmid KW, Hoyer PF. Immigrating progenitor cells contribute to human podocyte turnover. Kidney Int 2007;72:1468-73.

  • 28. Ohse T, Vaughan MR, Kopp JB, Krofft RD, Marshall CB, Chang AM, et al. De novo expression of podocyte proteins in parietal epithelial cells during experimental glomerular disease. Am J Physiol Renal Physiol 2010;298:F702-11.

  • 29. Kriz W. The pathogenesis of ‘classic’ focal segmental glomerulosclerosis-lessons from rat models. Nephrol Dial Transplant 2003;18 (Suppl 6):vi39-44.

  • 30. Hara M, Yamamoto T, Yanagihara T, Takada T, Itoh M, Adachi Y, et al. Urinary excretion of podocalyxin indicates glomerular epithelial cell injuries in glomerulonephritis. Nephron 1995;69:397-403.

  • 31. Hara M, Yanagihara T, Itoh M, Matsuno M, Kihara I. Immunohistochemical and urinary markers of podocyte injury. Pediatr Nephrol 1998;12:43-8.

  • 32. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Ebihara I, et al. Urinary excretion of podocytes in patients with diabetic nephropathy. Nephrol Dial Transplant 2000;15:1379-83.

  • 33. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, et al. Urinary podocytes for the assessment of disease activity in lupus nephritis. Am J Med Sci 2000;320:112-6.

  • 34. Nakamura T, Ushiyama C, Suzuki S. Effect of angioten-sin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy. Am J Nephrol 2000;20:373-9.

  • 35. Sekulic M, Pichler-Sekulic S. A compendium of urinary biomarkers indicative of glomerular podocytopathy. Patholog Res Int 2013; 2013:782395.

  • 36. Wickman L, Afshinnia F, Wang SQ, Yang Y, Wang F, Chowdhury M, et al. Urine podocyte mRNAs, proteinuria, and progression in human glomerular diseases. J Am Soc Nephrol 2013;24:2081-95.

  • 37. Hara M, Yanagihara T, Kihara I. Significance of urinary binucleated podocytes in IgA nephropathy. Nephrology 2001;6:A15.

  • 38. Ponchiardi C, Fall B, Scott R, Uhrich S, Mauer M, Whitley C, et al. Podocyturia correlates with proteinuria in patients with Fabry disease (FD) and is a potential biomarker of Fabry nephropathy. Mol Genet Metab 2013;108:S76-7.

  • 39. Ryu M, Mulay S, Misoge N, Gross O, Anders H. Tumor necrosis factor-β drives Alport glomerulosclerosis in mice by promoting podocyte apoptosis. J Pathol 2012;226:120-31.

  • 40. Endlich N, Kress K, Reiser J, Uttenweiler D, Kriz W, Mundel P, et al. Podocytes respond to mechanical stress in vitro. J Am Soc Nephrol 2001;12:413-22.

  • 41. Grishman E, Churg J. Focal glomerular sclerosis in nephrotic patients: An electron microscopic study of glomerular podocytes. Kidney Int 1975;7:111-22.

  • 42. Hara M, Yanagihara T, Hirayama Y, Ogasawara S, Kurosawa H, Sekine S, et al. Podocyte membrane vesicles in urine originate from tip vesiculation of podocyte microvilli. Hum Pathol 2010;41:1265-75.

  • 43. Böttinger E. TGF-beta in renal injury and disease. Semin Nephrol 2007;3:309-20.

  • 44. Maestroni S, Maestroni A, Dell’Antonio G, Gabellini D, Terzi S, Spinello A, et al. Viable podocyturia in healthy individuals: Implications for podocytopathies. Am J Kidney Dis 2014;64:1003-5.

  • 45. Jopling C, Boue S, Izpisua Belmonte JC. Dedifferentiation, transdifferentiation and reprogramming: Three routes to regeneration. Nat Rev Mol Cell Biol 2011;12:79-89.

  • 46. Herman-Edelstein M, Thomas MC, Thallas-Bonke V, Saleem M, Cooper ME, Kantharidis P. Dedifferentiation of immortalized human podocytes in response to transforming growth factor-b: A model for diabetic podocytopathy. Diabetes 2011;60:1779-88.

  • 47. Meyer TW, Bennett PH, Nelson RG. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria. Diabetologia 1999;42:1341-4.

  • 48. Steffes MW, Schmidt D, McCrery R, Basgen JM. Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney Int 2001;59:2104-13.

  • 49. Trimarchi H, Muryan A, Raña MS, Paggi P, Lombi F, Forrester M, et al. Proteinuria and its relation to diverse biomarkers and body mass index in chronic hemodialysis. Int J Nephrol Renovasc Dis 2013;6:113-9.

Journal + Issues