THE MEANING OF «POTENTIALLY UREMIC TOXINS» IN THE DEVELOPMENT OF PROTEIN-ENERGY MALNUTRITION IN HEMODIALYSIS PATIENTS

Basic mechanisms of the development of protein-energy malnutrition in patients with chronic kidney disease (CKD) in the state of terminal renal insufficiency, with hemodialysis (HD) treatment are shortly evaluated. The role of leptin is described in detail. Leptin is anorexigenic hormone, which is secreted by blood adipocytes in various quantities and controls the mass of adipose tissue, by means of lipid exchange stimulation in the organism. Leptin, by influencing the arcaute nucleus of hypothalamus, leads to decreased food intake and maintenance of lipid exchange on a normal level. Leptin is perceived as hormone that’s prevents overweight. At the same time in most overweight patients was noticed an increased level of leptin in blood, and such hyperleptinemia was interpreted as a proof of decreased sensitivity to physiologic action of hormone. In hemodialysis patients was noticed a higher level of circulating leptin, as opposed to healthy group. Keeping in mind that leptin participates in the regulation of food intake and energy output, was made an assumption that hyperleptinemia in patients with end stage renal disease, can be one of the factors, leading to anorexia and development of malnutrition (or cohexy). Theoretically, this interactions seem quite logical, but the results of the investigations on the connections of hyperleptinemia and excess of malnutrition in end stage renal disease were contradicting. The presence of such contradictions necessitates a more further scientific investigations in such direction.

1. Chertow GM, Bullard A, Lazarus JM. Nutrition and the dialysis prescription. Am J Nephrol 1996; 16(1) 79-89

2. Ikizler TA, Hakim RM. Nutrition in end-stage renal disease. Kidney Int 1996; 50(2): 343-357

3. Walser M. Dialysis and protein malnutrition. Kidney Int 1999; 56(1): 353

4. Hakim RM. Clinical implications of hemodialysis membrane biocompatibility. Kidney Int 1993; 44(3) 484-494

5. Kopple JD. National Kidney Foundation K/DOQI clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis 2001; 37: S66-S70

6. Bergstrцm J. Anoxia in dialysis patients. Seminars Nephrol 1996; 16(3): 222-229

7. Румянцев АШ, Козлов ВВ, Казначеева ИГ. Средние молекулы. В: Рябов СИ, ред. Лечение хронической почечной недостаточности. Фолиант, СПб, 1997; 345-367

8. Vanholder RC, De Smet RV, Glorieux GL et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 2003; 63(5): 1934-1943

9. Zhang Y, Proenca R, Maffei M et al. Positional cloning of the mouse obiese gene and its human homologue. Nature 1994; 372(6505): 425-432

10. Kershaw ES, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89(6): 2548-2556

11. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocrind Rev 2000; 21: 697-738

12. Fain JN, Madan AK, Hiler ML et al. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissue of obese humans. Endocrinology 2004; 145: 2273-2282

13. Панков ЮА. Лептин – новый гормон в эндокринологии. Успехи физиологических наук 2003; 34(2): 3-20

14. Senaris R, Garcia-Caballero T, Casabiell X et al. Synthesis of leptin in human placenta. Endocrinology 1997; 138(10): 4501-4504

15. Wiecek A, Kokot F, Chudek J, Adamczak M. The adipose tissue – a novel endocrine organ of interest to the nephrologists. Nephrol Dial Transplant 2002; 17(2): 191-195

16. Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002; 26: 1407-1433

17. Brennan AM, Mantzoros CS. Drug insight: the role of leptin in human physiology and pathophysiology – emerging clinical applications. Nat Clin Pract Endocrinol Metab 2006; 2 (6): 318-327

18. Thorn SR, Meyer MJ, van Amburgh ME, Boisclair YR. Effect of estrogen on leptin and expression of leptin receptor transcripts in prepubertal dairy heifers. J Dairy Sci2007; 90(8): 3742-3750

19. Hong SC, Yoo SW, Cho GJ, Kim T et al. Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women. Menopause 2007; 14(5): 835-840

20. Fruhbeck G, Jebb SA, Prentice AM. Leptin: physiology and pathophysiology (Review). Clin Physiol (Oxford) 1998; 18(5): 399-419

21. Ahima RS, Flier JS. Leptin. Ann Review Physiol (Palo Alto, CA) 2000; 62: 413-437

22. Tartaglia LA, Dembski M, Weng X et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263-1271

23. Chen H, Charlat O, Tartaglia LA et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84: 491-495

24. Lee GH, Proenca R, Montez JM et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379: 632-635

25. Bjorback C, Kahn BB. Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res 2004; 59: 305-331

26. Le Cava A, Alviggi C, Matarese G. Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med 2004; 82(1): 4-11

27. Zeibel RL. The role of leptin in the control of body weight. Nutrition Reviews 2002; 60(10,pt2): S15-S19

28. Ren J. Leptin and hyperleptinemia – from friend to foe for cardiovascular function (review). J Endocrinol (Bristol)2004; 181(1): 1-10

29. De Rosa V, Procaccini C, Cali G et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity 2007; 26(2): 241-255

30. Surmacz E. Obesity hormone leptin: a new target in breast cancer? Breast Cancer Res 2007; 9(1): 301

31. Bossola M, Muscaritoli M, Tazza L et al. Does leptin contribute to uraemic cachexia? Nephrol Dial Transplant 2006; 21(4): 1125-1126

32. Nordfors L, Lonnqvist F, Heimburger O et al. Low leptin gene expression and hyperleptinemia in chronic renal failure. Kidney Int 1998; 54: 1267-1275

33. Plata-Salaman CR. Leptin and anorexia in renal insufficiency. Nephron Clinical Practice 2004; 97(3): 73-75

34. Mak RH, Cheung W, Cone RD, Marks DL. Leptin and inflammation-associated cachexia in chronic kidney disease. Mini review Kidney Int (New York, NY)2006; 69(5): 794-797

35. Kokot F, Adamczak M, Wiecek A. Plasma leptin concentration in kidney transplant patients during the early posttransplant period. Nephrol Dial Transplant 1998; 13: 2276-2280

36. Stenvinkel P, Lindholm B, Lonngvist F et al. Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass. J Am Soc Nephrol2000; 1: 1303-1309

37. Don BR, Rosales LM, Levine NW et al. Leptin is a negative acute phase protein in chronic hemodialysis patients. Kidney Int 2001; 59: 1114-1120

38. Kayardi M, Icagasioglu S, Yilmaz A, Candan F. Serum leptin levels and malnutrition in patients with chronic renal failure. Saudi Medical Journal (Riyadh) 2006; 27(4): 477-481

39. Cheung W, Yu PX, Little BM ef al. Role of leptin and melanocortin signaling in uremia-associated cachexia. J Clin Invest 2005; 115: 1659-1665

40. Pecoits-Filho R, Nordfors L, Heimburger О ef al. Soluble leptin receptors and serum leptin in end-stage renal disease: elationship with inflammation and body composition. Eur J Clin Invest2002; 32: 811-817

41. Voegeling S, Fantuzzi G. Regulation of free and bound leptin and soluble leptin receptors during inflammation in mice. Cytokine2 001; 14: 97-103

42. Huang QH, Hruby VJ, Tatro JB. Role of central melanocortins in endotoxin-induced anorexia. Am J Physiol 1999; 276: R864-R871