#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The effect of statins on podocytes in nephrotic syndrome


Authors: Peter Habara 1,3;  Marie Claire Šmůlová 1;  Pavla Fialová 1;  Jan Krtil 2,3;  Karolína Krátká 3;  Ivan Rychlík 3
Authors‘ workplace: Centrální laboratoře, úsek klinické biochemie FNKV, Praha 1;  Ústav biochemie a laboratorní diagnostiky 1. LF UK a VFN v Praze 2;  I. interní klinika FNKV a 3. LF UK, Praha 3
Published in: AtheroRev 2019; 4(3): 145-152
Category:

Overview

Nephrotic syndrome frequently accompanies glomerulnephritides, including diabetic nephropathy and obestity-induced glomerulopathy, which are marked by pathology at the level of the podocyte. Podocytes are the main cellular component of renal parenchyme facilitating the filtration of blood not only through the inherent structural component they provide the glomerular filtration membrane itself, but also through their active role in regulating it. In the last few years, the pathophysio­logy of podocytes has been studied extensively as well as their role as a potential diagnostic tool. In light of this, it has been determined that the presence of podocytes in urine correlates to a state of active renal disease leading to nephrotic sydnrome, the consequences of which can be severe. That is to say, in the setting of nephrotic sydrom resistant to treatment, the threat of progressive disease culminating in in end-stage renal failure is high as well the damaging systemic effects of the resulting metabolic disruption. Dyslipidemia, coagulopathy and changes to the renin-angiotensin-aldosterone system are the most studied metabolic disturbances associated with nephrotic syndrome. In all of thesesituations, compensatory mechanisms to restore homeostasis are engaged, which can become dangerously damaged in wake of the accelerateddevelopment of atherosclerotic changes and their ensuing complications, due to a prolonged state of disease. Statins--especially their pleiotropic effects-offer promising therapeautic potential, which needs to be further explored and utilized more extensively in the clinical setting.

Keywords:

combination therapy – Atherosclerosis – podocyte – podocalyxin – statins – dyslipidemie


Sources
  1. Barrisoni L, Mundel P. Podocyte biology and the emerging understanding podocytes diseases. Am J Nephrol 2003; 23(5): 353–360. Dostupné z DOI: <http://dx.doi.org/10.1159/000072917>.
  2. Mundel P, Shankland SJ. Podocytes Biology and Response to Injury. J Am Soc Nephrol 2002; 13(12): 3005–3015. Dostupné z DOI: <http://dx.doi.org/10.1097/01.asn.0000039661.06947.fd>.
  3. Pavenstadt H, Kriz W, Kretzler M. Cell Biology of the Glomerular podocyte. Physiol Rev 2003; 83(1): 253–307. Dostupné z DOI: <http://dx.doi.org/10.1152/physrev.00020.2002>.
  4. Kriz W, Shirato I, Nagata M et al. The podocyte‘s response to stress: the enigma of foot process effacement. Am J Physiol Renal Physiol 2013; 304(4): F333-F347. Dostupné z DOI: <http://dx.doi.org/10.1152/ajprenal.00478.2012>.
  5. Hara M, Yanagihara T, Hirayama Y et al. Podocyte membrane vesicles in urine originate from tip vesiculation of podocyte microvilli. Hum Pathol 2010; 41(9): 1265–1275. Dostupné z DOI: <http://dx.doi.org/10.1016/j.humpath.2010.02.004>.
  6. Faul C, Asanuma K, Yanagida-Asanuma E et al. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol 2007; 17(9): 428–437. Dostupné z DOI: <http://dx.doi.org/10.1016/j.tcb.2007.06.006>.
  7. Schlüter MA, Margolis B. Apicobasal polarity in the Kidney. Exp Cell Res 2012 May 15;318(9): 1033–1039. Dostupné z DOI: <http://dx.doi.org/10.1016/j.yexcr.2012.02.028>.
  8. Garg P, Holzman LB. Podocytes: gaining a foothold. Exp Cell Res 2012; 318(9): 955–963. Dostupné z DOI: <http://dx.doi.org/10.1016/j.yexcr.2012.02.030>.
  9. Huber TB, Hartleben B, Winkelmann K et al. Loss of podocyte aPKClambda/iota causes polarity defects and nephrotic syndrome. J Am Soc Nephrol 2009; 20(4): 798–806. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2008080871>.
  10. Joberty G, Petersen C, Gao L et al. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2000; 2(8): 531–539. Dostupné z DOI: <http://dx.doi.org/10.1038/35019573>.
  11. Jones N, New LA, Fortino MA et al. Nck proteins maintain the adult glomerular filtration barrier. J Am Soc Nephrol 2009; 20(7): 1533–1543. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2009010056>.
  12. Takeda T. Podocyte cytoskeleton is connected to the integral membrane protein podocalyxin through Na+/H+-exchanger regulatory factor 2 and ezrin. Clin Exp Nephrol 2003; 7(4): 260–269. Dostupné z DOI: <http://dx.doi.org/10.1007/s10157–003–0257–8>.
  13. Aaltonen P, Holthofer H. Nephrin and related protein in th pathogenesis of nephropathy. Drug Discovery Today: Disease Mechanisms 2007; 4(1): 21–27. Dostupné z DOI: <https://doi.org/10.1016/j.ddmec.2007.06.003>.
  14. Patrakka J, Tryggvason K. Nephrin – a unique structural and signaling protein of the kidney filter. Trends Mol Med 2007; 13(9): 396–403. Dostupné z DOI: <http://dx.doi.org/10.1016/j.molmed.2007.06.006>.
  15. Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reasesment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2007; 2(3): 529–542. Dostupné z DOI: <http://dx.doi.org/10.2215/CJN.04121206>.
  16. Tesař V, Honsová E. Glomerulopatie. In: Tesař V, Schűck O. Klinická nefrologie. Grada: Praha 2006: 179–247. ISBN 8024705036.
  17. Hara M, Yamamoto T, Yanagihara T et al. Urinary excretion of podocalyxin indicates glomerular epithelial cell injuries in glomerulonephritis. Nephron 1995; 69(4): 397–403. Dostupné z DOI: <http://dx.doi.org/10.1159/000188509>.
  18. Habara P, Marečková H, Sopková Z et al. A Novel Method for the Estimation of Podocyte Injury: Podocalyxin-Positive Elements in Urine. Folia Biologica (Praha) 2008; 54(5): 162–167.
  19. Ye H, Bai X, Gao H et al. Urinary podocalyxin positive element occurs in the early stage of diabetic nephropathy. J Diabetes Complications 2014; 28(1): 96–100. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jdiacomp.2013.08.006>.
  20. Suwanpen C, Nouanthong P, Jaruvongvanich V et al. Urinary podocalyxin, the novel biomarker for detecting early renal change in obesity. J Nephrol 2016; 29: 37–44. Dostupné z DOI: <http://dx.doi.org/10.1007/s40620–015–0199–8>.
  21. Vaziri ND. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences. Kidney Int 2016; 90(1): 41–52. Dostupné z DOI: <https://doi.org/10.1016/j.kint.2016.02.026>.
  22. Baigent C, Landray MJ, Reith C et al. [SHARP investigators]. The effect of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebocontrolled trial. Lancet 2011: 377(9784): 2181–2192. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(11)60739–3>.
  23. Solomon RJ, Natarajan MK, Doucet S et al. Cardiac Angiography in Renally Impaired Patients(CARE) Study. Circulation 2007; 115(25): 3189–3196.
  24. Amann K, Benz K. Statins-beyond lipids in CKD. Nephrol Dial Transplant; 2011; 26(2): 407–410. Dostupné z DOI: <http://dx.doi.org/10.1093/ndt/gfq662>.
  25. Buemi M, Nostro L, Crascì E et al. Statins in nephrotic syndrome: a new weapon against tissue injury. Med Res Rev 2005: 25(6): 587–609. Dostupné z DOI: <http://dx.doi.org/10.1002/med.20040>.
  26. Wei P, Grimm PR, Settles DC et al. Simvastatin reverses podocyte injury but not mesangial expansion in early stage type 2 diabetes mellitus. Ren Fail 2009; 31(6): 503–513. Dostupné z DOI: <http://dx.doi.org/10.1080/08860220902963848>.
Labels
Angiology Diabetology Internal medicine Cardiology General practitioner for adults

Article was published in

Athero Review

Issue 3

2019 Issue 3

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#