Serum lipids, lipoproteins, oxidative stress parameters and paraoxonase 1 (PON-1) activity in post-renal transplant patients (Tx) with stable renal function and Tx patients without and with statins therapy

Elżbieta Kimak; Janusz Solski; Iwona Baranowicz-Gąszczyk; Andrzej Książek

Authors

Elżbieta Kimak Department of Laboratory Diagnostic, Medical University of Lublin, Poland Author https://orcid.org/0000-0001-5649-0916
Janusz Solski Department of Laboratory Diagnostic, Medical University of Lublin, Poland Author https://orcid.org/0000-0003-2884-1509
Iwona Baranowicz-Gąszczyk Department of Clinical Nephrology, Medical University of Lublin, Poland Author
Andrzej Książek Department of Clinical Nephrology, Medical University of Lublin, Poland Author

Keywords:

lipids, lipoproteins, paraoxonase-1 activity, oxidative stress, post-renal transplant

Abstract

Disturbances in the metabolism of the lipoproteins in post-renal transplant patients accelerate atherosclerosis and cardiovascular diseases, which are one of the major causes of death from these diseases. Serum concentration of lipid, lipoprotein, leptin, total peroxide (OxyStat), and paraoxonase-1 activity (PON1) were determined in 11 post-renal transplant patients (Tx) with stable renal function and normolipidemia, 25 Tx patients without statins therapy, 31 Tx patients with statins therapy and 53 controls. Tx patients received prednisone and Cyclosporine A or prednisone and prograf. Tx patients with stable renal function and normolipidemia had favourable clinical and laboratory parameters and lipid and lipoprotein profiles than those without statins and with statins therapy. Tx patients with dyslipidemia had disturbed lipoprotein concentration and composition, and triglyceride-rich lipoproteins (TRLs) and HDL metabolism. VLDL, IDL, LDL and HDL particles were smaller, denser and more susceptible to modification and oxidation. They were exposed to oxidative stress, and the anti-oxidative role of PON-1 was weakened. However, Tx patients with statins therapy had a lower OxyStat level and higher PON-1 basal and salt stimulation activity than Tx patients without statins therapy. We suggest that oxidative modification of HDL can affect their ability to reduce antioxidant and PON-1 activity, but statin treatment improves them, which could prevent progression of atherosclerosis and chronic allograft failure. However, future studies are required.

References

1. Blatter., Garin M-C., Moren X.: Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I. J. Lipid. Res., 47, 515, 2006.

2. Chan D.C., Chen M.M., Ooi M.M., Watts G.F.: An ABC of apolipoprotein CIII: a clinically useful new cardiovascular risk factor? Int. J. Clin Pract., 62, 799, 2008.

3. Draganov D., Teiber J.F., Speelman A. et al.: Human paraoxonase (PON1, PON2, and PON3 are lactonases with overlapping and distinct substrate specificities. J. Lipid. Res., 46, 1239, 2005.

4. Fellström B.: Risk factors for and management of post-transplantation cardiovascular disease. BioDrugs, 15, 261, 2001.

5. Friedewald W.T., Levy R.I., Fredrickson D.S.: Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin. Chem., 18, 499, 1972.

6. Furlong C.E., Richter R.J., Seidel S.L. et al.: Spectrophotometric assays for the enzymatic hydrolysis of the active metabolities of chlorpyrifos and parathion by plasma paraoxonase/arylesterase. Anal. Biochem., 180, 242, 1989.

7. Ghaznavi R., Zahmatkesh M., Kadhodaee M. et al.: Cyclosporine effects on the antioxidant capacity of rat renal tissues. Transplant. Proc., 39, 866, 2007.

8. Gou L., Fu M., Xu Y. et al.: Alterations of HDL subclasses in endogenous hypertriglyceridemia. Am. Heart. J., 150, 1039, 2005.

9. Harangi M., Mirdamadi H.Z., Seres I. et al.: Atorvastatin effect on the distribution of high-density lipoprotein subfraction and human paraoxonase activity. Transplant. Res., 153, 198, 2009.

10. Jabbari A., Argani H., Ghorbanihaghjo A., Mahdavi R.: Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in renal transplant recipients. Lipid Health Dis., 4, 11, 2005.

11. Jia L., Long S., Fu M. et al.: Relationship between total cholesterol/high-density lipoprotein cholesterol ratio, triglyceride/high-density lipoprotein ratio, and high-density lipoprotein subclasses. Metabolism., 55, 1141, 2006.

12. Jurek A., Turyna B., Kubit P., Klein A.: The ability of HDL to inhibit VCAM-1 expression and oxidized LDL uptake is impaired in renal patients. Clin. Biochem., 41, 1015, 2008.

13. Kanbay M., Turgut F., Covic A., Goldsmith D.: Statin treatment for dyslipidemia in chronic kidney disease and renal transplantation: a review of the evidence. J. Nephrol., 22, 598, 2009.

14. Kassai A., Illyes L., Mirdamadi H.Z. et al.: The effect of atorvastatine therapy on lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein and the antioxidant paraoxonase. Clin. Biochem., 40, 1, 2007.

15. Kimak E., Książek A., Solski J.: Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure. Clin. Chem. Lab. Med., 44, 64, 2006.

16. Kimak E., Książek A., Baranowicz-Gąszczyk I., Solski J.: Disturbed lipids, lipoproteins and triglyceride rich-lipoproteins as well as fasting and nonfasting non-high–density lipoprotein cholesterol in post-renal transplant patients. Ren. Fail., 29, 705, 2007.

17. Kimak E., Solski J., Baranowicz-Gąszczyk I., Książek A.: Serum lipid, leptin, parameters of oxidative stress and PON-1 activity in post-renal transplant patients. Annales UMCS. Sect. DDD, 21, 355, 2008.

18. Kimak E., Gierszon M., Hałabiś M., Markowicz R., Baranowicz-Gąszczyk I.: Serum paraoxonase activity in hemodialysis patients with chronic renal failure. Annales UMCS. Sect. DDD, 19, 223, 2006.

19. Kimak E., Hałabiś M.: Serum hypertriglyceridemia as an important risk factor of chronic allograft failure in post-renal transplant patients. Annales UMCS, Sect. DDD, 22, 115, 2009.

20. Kimak E., Hałabiś M., Baranowicz-Gąszczyk I.: Relationships between serum lipid, lipoprotein, triglyceride-rich lipoprotein, and high-density lipoprotein particles in post-renal transplant patients. JZUS-B, 11, 249, 2010.

21. Mirdamadi H.Z., Sztanek F., Derdak Z. et al.: The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters. Br. J. Clin. Pharmacol. 66, 366, 2008.

22. Moratalla J.M.O., Lanatta C.F., Morilla B. et al. Left Ventricular structure and function in long-term kidney transplantation: the influence of glucose metabolism and oxidative stress. Transplant. Proc., 40, 2912, 2008.

23. Moreno J.M., Ruiz M.C., Ruiz N. et al.: Modulation factors of oxidative status in stable renal transplantation. Transplant. Proc., 37, 1428, 2005.

24. Nafar M., Farrokhi F., Vaezi M. et al.: Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection. Int. Urol .Nephrol., 41, 687, 2009.

25. Navaneethan S.D., Perkovic V., Johnson D.W. et al.: HMG CoA reductase inhibitors (statins) for kidney transplant recipients. Cochrane Database Syst. Rev., 15, CD005019, 2009

26. Onat A., Hergenc G., Sansoy V., et al.: Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis. 168, 81, 2003.

27. Paraskevas K.I.: Statin therapy in peritoneal dialysis patients: effects beyond lipid lowering. Int. Urol. Nephrol., 40, 165, 2008.

28. Perrea D.N., Moulakakis K.G., Poulakou M.V. et al.: Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function. Int. Urol. Nephrol., 38, 343, 2006.

29. Perrea D.N., Moulakakis K.G., Poulakou M.V. et al.: Correlation between lipid abnormalities and immunosuppressive therapy in renal transplant recipients with stable renal function. Int. Urol. Nephrol., 40, 521, 2008

30. Poulakou M., Paraskvas K.I., Vlachos I.S. et al.: Effect of statins on serum apolipoprotein J and paraoxonase-1 levels in patients with ischemic heart disease undergoing coronary angiography. Angiology, 59, 137, 2008.

31. Proudfoot J.M., Barden A.E., Loke W.M. et al. HDL is the major lipoprotein carrier of plasma F2- isoprostanes. J. Lipid. Res., 50, 716, 2009.

32. Rashid S., Barrett P.H.R., Uffelman K.D. et al.: Lipolytically modified triglyceride-enriched HDLs are rapidly cleared from the circulation. Atheroscler. Thromb. Vasc. Biol., 22, 483, 2002.

33. Ruiz M.C, Medina A., Moreno J.M. et al.: Relationship between oxidative stress parameters and atherosclerotic sign in the carotid artery of stable renal transplant patients. Transplant. Proc., 37, 3796, 2005.

34. Sacks F.M, Alaupovic P., Moye L.A. et al.: VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation, 102, 1886, 2000.

35. Sadideen H., Covic A., Goldsmith D.: Mineral and bone disorders after renal transplantation: a review. Int. Urol. Nephrol., 40, 171, 2008.

36. Saxena R., Yu X., Giraldo M. et al.: Renal transplantation in the elderly. Int. Urol. Nephrol., 41, 195, 2009.

37. Tory R., Sachs-Barrable K., Goshko C-B. et al.: Tacrolimus-induced elevation in plasma triglyceride concentration after administration to renal transplant patients in partially due to a decrease in lipoprotein lipase activity and plasma concentration. Transplantation, 88, 62, 2009.

38. Wang L., Gill R., Pedersen T. et al.: Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation. J. Lipid. Res., 50, 204, 2009.

39. Wissing K.M., Abramowicz D., Broders N., Vereerstraeten P.: Hypercholesterolemia is associated with increased kidney graft loss caused by chronic rejection in male patients with previous acute rejection. Transplantation, 70, 464, 2000.

40. Yang Y., Yan B., Fu M. et al.: Relationship between plasma lipid concentrations and HDL subclasses. Clin. Chim. Acta, 354, 49, 2005.