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Low protein Z levels in children with nephrotic syndrome

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Abstract

Acquired deficiency of anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic syndrome (NS). Protein Z (PZ) is a single-chain vitamin K-dependent glycoprotein. Low PZ levels are reported to be a risk factor for thrombosis. The aim of this study was to investigate protein Z and other natural anticoagulant levels in children with NS. Thirty children aged between 1.5 and 12 years with NS (Groups I and II) and 19 age-and-sex-matched healthy controls (Group III) were enrolled into the study. Patients were divided into two groups: Group I (proteinuria >40 mg/m2/hr) and Group II (patients in remission). Plasma PZ levels in Group I were significantly lower than Group II (p=0.009) and group III (p=0.018). Plasma levels of AT III for Group I were significantly lower than for Groups II and III (p=0.009, p=0.005, respectively). Protein C levels in Group I were higher than in Group II and Group III (p=0.002, p=0.000, respectively). Protein Z levels positively correlated with serum total protein and albumin levels (p=0.003, p=0.003, respectively) and negatively with the degree of proteinuria (p=0.000). Protein Z levels were positively correlated with AT III (r=0.037, p=0.04). Along with the other coagulation abnormalities, decreased protein Z may contribute to increased risk of thromboembolic complications in children with NS. The negative correlation between proteinuria and PZ level suggests the possibility of renal PZ loss. Further studies are needed to investigate the mechanism and role of decreased PZ in NS.

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References

  1. Mehls O, Andrassy K, Koderisch J, Herzog U, Ritz E (1987) Hemostasis and thromboembolism in children with nephrotic syndrome: differences from adults. J Pediatr 110:862–867

    Article  CAS  Google Scholar 

  2. Harris RC, Ismail N (1994) Extrarenal complications of the nephrotic syndrome. Am J Kidney Dis 23:477–497

    Article  CAS  Google Scholar 

  3. Hoyer PF, Gonda S, Barthels M, Krohn HP, Brodehl J (1986) Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paediatr Scand 75:804–810

    Article  CAS  Google Scholar 

  4. Özkayýn N, Mir S, Kavakli K (2004) Hypercoagulability risk factors in children with minimal change disease and the protective role of protein-C activity. Int Urol Nephrol 36:599–603

    Article  Google Scholar 

  5. Singhal R, Brimble KS (2005) Thromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management. Thromb Res DOI: 10.1016/j.thromres.2005.03.030

  6. Citak A, Emre S, Sairin A, Bilge I, Nayir A (2000) Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 14:138–142

    Article  CAS  Google Scholar 

  7. Han X, Fiehler R, Broze GJ Jr (2000) Characterization of the protein Z-dependent protease inhibitor. Blood 96:3049–3055

    Article  CAS  Google Scholar 

  8. Han X, Huang ZF, Fiehler R, Broze GJ Jr (1999) The protein Z-dependent protease inhibitor is a serpin. Biochemistry 24:11073–11078

    Article  Google Scholar 

  9. Kemkes-Matthes B, Matthes KJ (2001) Protein Z. Semin Thromb Hemost 27:551–556

    Article  CAS  Google Scholar 

  10. Broze GJ Jr (2001) Protein Z-dependent regulation of coagulation. Thromb Haemost 86:8–13

    Article  CAS  Google Scholar 

  11. Al-Shanqeeti A, van Hylckama Vlieg A, Berntorp E, Rosendaal FR, Broze GJ Jr (2005) Protein Z and protein Z-dependent protease inhibitor. Determinants of levels and risk of venous thrombosis. Thromb Haemost 93:411–413

    Article  CAS  Google Scholar 

  12. Vasse M, Guegan-Massardier E, Borg JY, Woimant F, Soria C (2001) Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 24:933–944

    Article  Google Scholar 

  13. International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at the time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165

    Article  Google Scholar 

  14. Tkaczyk M, Baj Z, Zbigniew (2002) Surface markers of platelet function in idiopathic nephritic syndrome in children. Pediatr Nephrol 17:673–677

    Article  Google Scholar 

  15. Wasilewska AM, Zoch-Zwierz WM, Tomaszewska B, Biernacka A (2005) Platelet-derived growth factor and platelet profiles in childhood nephrotic syndrome. Pediatr Nephrol 20:36–41

    Article  Google Scholar 

  16. Hogg PJ, Stenflo J (1991) Interaction of vitamin K-dependent protein Z with thrombin. Consequences for the amidolytic activity of thrombin and the interaction of thrombin with phospholipid vesicles. J Biol Chem 15:10953–10958

    Google Scholar 

  17. Kobelt K, Biasiutti FD, Mattle HP, Lammle B, Wuillemin WA (2001) Protein Z in ischaemic stroke. Br J Haematol 114:169–173

    Google Scholar 

  18. Malyszko J, Malyszko JS, Mysliwiec M (2002) Markers of endothelial cell injury and thrombin activatable fibrinolysis inhibitor in nephrotic syndrome. Blood Coagul Fibrinolysis 13:615–621

    Article  CAS  Google Scholar 

  19. al-Mugeiren MM, Gader AM, al-Rasheed SA, Bahakim HM, al-Momen AK, al-Salloum A (1996) Coagulopathy of childhood nephrotic syndrome-a reappraisal of the role of natural anticoagulants and fibrinolysis. Haemostasis 26:304–310

    CAS  PubMed  Google Scholar 

  20. Llach F (1985) Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 28:429–439

    Article  CAS  Google Scholar 

  21. Mannucci PM, Valsecchi C, Bottasso B, D’Angelo A, Casati S, Ponticelli C (1986) High plasma levels of protein C activity and antigen in the nephrotic syndrome. Thromb Haemost 28:31–33

    Google Scholar 

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Acknowledgements

We thank the Eczacıbaşı–Baxter Company for their kind support of this study. This study was presented as a poster presentation at the 39th Annual Meeting of ESPN in İstanbul, 10–13 September 2005, and published as an abstract in Pediatric Nephrology (2005) C57.

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Correspondence to Ozan Özkaya.

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Özkaya, O., Bek, K., Fışgın, T. et al. Low protein Z levels in children with nephrotic syndrome. Pediatr Nephrol 21, 1122–1126 (2006). https://doi.org/10.1007/s00467-006-0167-6

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  • DOI: https://doi.org/10.1007/s00467-006-0167-6

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