Regular exercise training decreases asymmetric dimethylarginine after kidney transplantation

Česká verzia

Authors: V. Teplan ^1,2; A. Mahrová ³; K. Švagrová ³; J. Racek ⁴; R. Gürlich ⁵; V. Teplan Jr ⁵; L. Šenolt ⁶; M. Štollová ¹
Authors place of work: Klinika nefrologie Transplantcentra IKEM Praha, přednosta prof. MUDr. Ondřej Viklický, CSc. ¹; Subkatedra nefrologie IPVZ Praha, vedoucí prof. MUDr. Vladimír Teplan, DrSc. ²; Laboratoř sportovní motoriky Fakulty tělesné výchovy a sportu UK Praha, přednosta prof. Ing. Václav Bunc, CSc. ³; Ústav klinické biochemie a hematologie Lékařské fakulty UK a FN Plzeň, přednosta prof. MUDr. Jaroslav Racek, DrSc. ⁴; Chirurgická klinika 3. lékařské fakulty UK a FN Královské Vinohrady Praha, přednosta prof. MUDr. Robert Gürlich, CSc. ⁵; Revmatologický ústav Praha, ředitel prof. MUDr. Karel Pavelka, DrSc. ⁶
Published in the journal: Vnitř Lék 2012; 58(9): 640-646
Category: Original Contributions

Summary

Background:
Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine are elevated in patients undergoing kidney transplantation and may contribute to vascular complications. In this study we tested the hypothesis that elevated asymmetric dimethylarginine can be reduced in patients after kidney transplantation by early regular physical exercise. Selected cytokines and metabolic parameters were also analysed.

Methods:
Plasma samples for analysis of asymmetric dimethylarginine, adiponectin, leptin, soluble leptin receptor, resistin, visfatin, CRP, TNFα and selected metabolic parameters were obtained from randomly selected sixty eight patients after kidney transplantation who agreed to participate in a supervised aerobic exercise program for six months. Samples were collected before the training began (one month after surgery with stabilized graft function) and at six months after initiation. Sixty transplant patients matched for age, sex, HLA typing, duration of previous dialysis, history of cardiovascular disease and immunosupression regimen who did not exercise regularly and did not participate in the training program were examined as controls.

Results:
There were no differences in elevated asymmetric dimethylarginine levels between both groups before the training program began. After six months of exercise, asymmetric dimethylarginine concentration in the exercising group I significantly decreased (3.5 ± 0.45 vs 2.11 ± 0.35 µmol/L, P < 0.01) and was also significantly lower comparing to non-exercising group II (2.11 ± 0.23 vs 3.25 ± 0.34 µmol/L, P < 0.01). We found significant changes in exercising group I: adiponectin (15.4 ± 6.6 vs 22.3 ± 6.2 mg/mL, P < 0.01), leptin (51.3 ± 11.2 vs 20.3 ± 9.2 ng/L, P < 0.01), soluble leptin receptor (24.6 ± 8.4 vs 46.1 ± 11.4 U/mL, P < 0.01), resistin (20.8 ± 10.1 vs 14.6 ± 6.4 mg/mL, P < 0.025) and visfatin (1.8 ± 0.2 vs 1.2 ± 0.01 ng/mL, P < 0.05). Blood lipids, HbA_1c, CRP and TNFα were also affected by the training program.

Conclusions:
Elevated asymmetric dimethylarginine level, selected adipocytokines and proinflammatory cytokines in patients after kidney transplantation were significantly influenced by early regular exercise. This regimen may decrease cardiovascular risk in patients after kidney transplantation.

Key words:
renal transplantation – physical exercise – ADMA – adiponectin – leptin – resistin – visfatin

Zdroje

1. Kielstein JT, Böger RH, Bode-Böger SM et al. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 2002; 13: 170–176.

2. Cooke JP. Asymmetrical dimethylarginine: the Uber marker? Circulation 2004; 109: 1813–1818.

3. Zoccali C, Kielstein J. Asymmetric dimethylarginine: a new player in the pathogenesis of renal disease? Curr Opin Nephrol Hypertens 2006; 15: 314–320.

4. Krzyzanowska K, Mittermayer F, Kopp HP et al. Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidity obese women. J Clin Endocrinol Metab 2004; 89: 6277–6281.

5. Meier-Kriesche HV, Arndorfer JA, Kaplan B. The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death. Transplantation 2002; 73: 70–74.

6. Boots JM, Christiaans MH, van Hooff JP. Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. Drugs 2004; 64: 2047–2073.

7. Axelsson J, Heimbürger O, Lindholm B et al. Adipose tissue and its relation to inflammation: the role of adipokines. J Ren Nutr 2005; 15: 131–136.

8. Zoccali C, Mallamaci F, Tripepi G. Adipose tissue as a source of inflammatory cytokines in health and disease: focus on end-stage renal disease. Kidney Int 2003; 63 (Suppl 84): S65–S68.

9. de Mattos AM, Prather J, Olyaei AJ et al. Cardiovascular events following renal transplantation: role of traditional and transplant-specific risk factors. Kidney Int 2006; 70: 757–764.

10. Fazelzadeh A, Mehdizadeh A, Ostovan MA et al. Incidence of cardiovascular risk factors and complications before and after kidney transplantation. Transplant Proc 2006; 38: 506–508.

11. Yilmaz MI, Saglam M, Caglar K et al. Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation. Transplantation 2005; 80: 1660–1666.

12. el-Agroudy AE, Wafa EW, Gheith OE et al. Weight gain after renal transplantation is a risk factor for patients and graft outcome. Transplantation 2004; 77: 1381–1385.

13. Weisberg SP, McCann D, Desai M et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796–1808.

14. Haluzik M, Parizkova J, Haluzik MM. Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res 2004; 53: 123–129.

15. Chudek J, Adamczak M, Karkoszka H et al. Plasma adiponectin concentration before and after successful kidney transplantation. Transplant Proc 2003; 35: 2186–2189.

16. Armstrong KA, Campbell SB, Hawley CM et al. Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients. Am J Transplant 2005; 5: 2710–2718.

17. Mittermayer F, Pleiner J, Krzyzanowska K et al. Regular physical exercise normalizes elevated asymmetrical dimethylarginine concentrations in patients with type 1 diabetes mellitus. Wien Klin Wochenschr 2005; 117: 816–820.

18. Fuhrmann I, Krause R. Principles of exercising in patients with chronic kidney disease, on dialysis and for kidney transplant recipients. Clin Nephrol 2004; 61 (Suppl 1): S14–S25.

19. Painter P, Carlson L, Carey S et al. Physical functioning and health-related quality of life changes with exercise training in hemodialysis patients. Am J Kidney Dis 2000; 35: 482–492.

20. Mahrova A, Švagrová K, Bunc V et al. Fyzická a psychická kondice u jedinců po transplantaci ledviny – význam časné pohybové intervence. Aktual Nefrol 2011; 17: 30–40.

21. Painter PL, Tomlanovich SL, Hector LA et al. A randomized trial of exercise training after renal transplantation. Transplantation 2002; 74: 42–48.

22. Korabiewska L, Lewandowska M, Juskowa J et al. Need for rehabilitation in renal replacement therapy involving allogenetic kidney transplantation. Transplant Proc 2007; 39: 2776–2777.

23. Mahrová A, Bunc V, Panáček V et al. Exercise rehabilitation during haemodialysis – clinical experience. Aktual Nefrol 2009; 15: 16–24.

24. McLaughlin T, Stühlinger M, Lamendola C et al. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J Clin Endocrinol Metab 2006; 91: 1896–1900.

25. Wiecek A, Kokot F, Chudek J et al. The adipose tissue: a novel endocrine organ of interest to the nephrologist. Nephrol Dial Transplant 2002; 17: 191–195.

26. Valkonen VP, Päivä H, Salonen JT et al. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 2001; 358: 2127–2128.

27. Lu TM, Ding YA, Lin SJ et al. Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 2003; 24: 1912–1919.

28. Tarnow L, Hovind P, Teerlink T et al. Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care 2004; 27: 765–769.

29. Niebauer J, Clark AL, Webb-Peploe KM et al. Home-based exercise training modulates pro--oxidant substrates in patients with chronic heart failure. Eur J Heart Fail 2005; 7: 183–188.

30. Achan V, Broadhead M, Malaki M et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humus and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003; 23: 1455–1459.

31. Ogawa T, Kimoto M, Sasaoka K. Purification and properties of a new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem 1989; 264: 10205–10209.

32. Kimoto M, Tsuji H, Ogawa T et al. Detection of NG, NG-dimethylarginine dimethylaminohydrolase in the nitric oxide-generating systems of rats using monoclonal antibody. Arch Biochem Biophys 1993; 300: 657–662.

33. Zaletel J, Cerne D, Lenart K et al. Renal functional reserve in patients with Type 1 diabetes mellitus. Wien Klin Wochenschr 2004; 116: 246–251.

34. Fukai T, Siegfried MR, Ushio-Fukai M et al. Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest 2000; 105: 1631–1639.

35. Lin KY, Ito A, Asagami T et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002; 106: 987–992.

36. Mittermayer F, Mayer BX, Meyer A et al. Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes. Diabetologia 2002; 45: 1372–1378.

37. Päivä H, Lehtimäki T, Laakso J et al. Plasma concentrations of asymmetric-dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism 2003; 52: 303–307.

38. Valkonen VP, Laakso J, Päivä H et al. Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events. Does statin treatment influence plasma ADMA levels? Atheroscler 2003; 4: 19–22.

39. Teplan V, Malý J, Gürlich R et al. Muscle and fat metabolism in obesity after kidney transplantation: no effect of peritoneal dialysis or hemodialysis. J Ren Nutr 2012; 22: 166–170.

40. Oflaz H, Turkmen A, Kazancioglu R et al. The effects of calcineurin inhibitors on endothelial function in renal transplant recipients. Clin Transplant 2003; 17: 212–216.

41. Sciacqua A, Candigliota M, Ceravolo R et al. Weight loss in combination with physical activity improves endothelial dysfunction in human obesity. Diabetes Care 2003; 26: 1673–1678.

42. Päivä H, Lehtimäki T, Laakso J et al. Dietary composition as a determinant of plasma asymmetric dimethylarginine in subject with mild hypercholesterolemia. Metabolism 2004; 53: 1072–1075.

43. Ito A, Egashira K, Narishige T et al. Renin--angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension. Jpn Circ J 2001; 65: 775–778.

44. Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein and adiponectin. Curr Opin Lipidol 2002; 13: 51–59.

45. Stenvienkel P, Marchlewska A, Pecoits-Filho R et al. Adiponectin in renal disease: relationship to phenotype and genetic variation of the gene encoding adiponectin. Kidney Int 2004; 65: 274–281.

46. Sharma AM, Chettey VT. Obesity, hypertension and insulin resistance. Acta Diabetol 2005; 42 (Suppl 1): S3–S8.

47. Senolt L, Krystufkova O, Hulejova H. The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy. Cytokine 2011; 55: 116–121.