Protein-energy wasting and mortality in chronic kidney disease

International Journal of Environmental Research and Public Health

Volumn 8, Issue 5, 2011, Pages 1631-1654

  Bonanni, Alice ^a   Mannucci, Irene ^a   Verzola, Daniela ^a   Sofia, Antonella ^a   Saffioti, Stefano ^a   Gianetta, Ezio ^b   Garibotto, Giacomo ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

Cardiovascular risk; Chronic kidney disease; Malnutrition; Protein energy wasting; Skeletal muscle

Indexed keywords

ADIPONECTIN; ADVANCED GLYCATION END PRODUCT; ADVANCED GLYCATION END PRODUCT RECEPTOR; ALBUMIN; BICARBONATE; C REACTIVE PROTEIN; CHOLESTEROL; CREATININE; GROWTH HORMONE; INSULIN; INTERLEUKIN 6; LEPTIN; METHIONINE; MUSCLE PROTEIN; MYOSTATIN; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; NITRIC OXIDE; PENTRAXIN 3; PREALBUMIN; SOMATOMEDIN C; TESTOSTERONE; THYROID HORMONE; TRANSFERRIN;

ACIDOSIS; AGING; AMINO ACID METABOLISM; ANOREXIA; BODY COMPOSITION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC KIDNEY DISEASE; DISEASE ASSOCIATION; DISEASE COURSE; ENDOTHELIAL DYSFUNCTION; HEMODIALYSIS; HUMAN; HYPOALBUMINEMIA; IMMUNE DEFICIENCY; INFECTION SENSITIVITY; INFLAMMATION; INSULIN RESISTANCE; KIDNEY METABOLISM; MORTALITY; MUSCLE REGENERATION; MUSCLE STEM CELL; OXIDATIVE STRESS; PERITONEAL DIALYSIS; PREDICTION; PROGNOSIS; PROTEIN CALORIE MALNUTRITION; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN METABOLISM; PROTEIN METHYLATION; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; STEM CELL; UREMIA; URINARY EXCRETION;

EID: 79957905431     PISSN: None     EISSN: 16604601     Source Type: Journal    
DOI: 10.3390/ijerph8051631     Document Type: Review

References (171)

1. Kalantar-Zadeh, K.; Abbott, K.C.; Kronenberg, F.; Anker, S.D.; Horwich, T.B.; Fonarow, G.C. Epidemiology of dialysis patients and heart failure patients. Semin. Nephrol. 2006, 26, 118-133.
2. Culleton, B.F.; Larson, M.G.; Wilson, P.W.; Evans, J.C.; Parfrey, P.S.; Levy, D. Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int. 1999, 56, 2214-2219.
3. Al-Aly, Z.; Zeringue, A.; Fu, J.; Rauchman, M.I.; McDonald, J.R.; El-Achkar, T.M.; Balasubramanian, S.; Nurutdinova, D.; Xian, H.; Stroupe, K. et al. Rate of Kidney function decline associates with mortality. J. Am. Soc. Nephrol. 2010, 21, 1961-1969.
4. Himmelfarb, J.; Ikizler, T.A. Hemodialysis. N. Engl. J. Med. 2010, 363, 1833-1845.
5. Foque, D.; Kalantar-Zadeh, K.; Kopple, J.D.; Canau, N; Chauveau, P.; Cuppari, L.; Franch, H.; Guarnieri, G.; Ikizler, T.A.; Kaysen, G. et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008, 73, 391-398.
6. Locatelli, F.; Manzoni, C.; Del Vecchio, L.; Di Filippo, S. Changes in the clinical condition of haemodialisys patients. J. Nephrol. 1999, 12, S82-S91.
7. Kalantar-Zadeh, K.; Block, G.; Humphreys, M.H.; Kopple, J.D. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003, 63, 793-808.
8. Kalantar-Zadeh, K.; Abbott, K.C.; Salahudeen, A.K.; Kilpatrick, R.D.; Horwich, T.B. Survival advantages of obesity in dialysis patients. Am. J. Clin. Nutr. 2005, 81, 543-554.
9. Kovesdy, C.P.; Kalantar-Zadeh, K. Why is protein-energy wasting associated with mortality in chronic kidney disease? Semin. Nephrol. 2009, 29, 3-14.
10. Stenvinkel, P. Inflammation in end-stage renal failure: could it be treated? Nephrol. Dial. Transpl. 2002, 17, S33-S38.
11. Chmielewski, M.; Carrero, J.J.; Qureshi, A.R.; Axelsson, J.; Heimburger, O.; Berglund, L.; Barany, P.; Rutkowski, B.; Lindholm, B.; Stenvinkel, P. Temporal discrepancies in the association between the apoB/apoA-I ratio and mortality in incident dialysis patients. J. Int. Med. 2009, 265, 708-716.
12. Chmielewski, M.; Verduijn, M.; Drechsler, C.; Lindholm, B.; Stenvinkel, P.; Rutkowski, B.; Boeschoten, E.W.; Krediet, R.; Dekker, F.W. Low Cholesterol in dialysis patients-causal factor for mortality or an effect of confounding? Nephrol. Dial. Transpl. 2011, doi:10.1093/ndt/gfr008.
13. Liu, Y.; Coresh, J.; Eustace, J.A.; Longenecker, J.C.; Jaar, B.; Fink, N.E.; Tracy, R.P.; Powe, N.R.; Klag, M.J. Association between cholesterol level and mortality in dialysis patients: Role of inflammation and malnutrition. JAMA 2004, 291, 451-459.
14. Contrerars, G.; Hu, B.; Astor, B.C.; Greene, T.; Erlinger, T.; Kusek, J.W.; Lipkowitz, M.; Lewis, J.A.; Randall, O.S.; Hebert, L. et al. Malnutrition-Inflammation modifies the relationship of cholesterol with cardiovascular disease. J. Am. Soc. Nephrol. 2010, 21, 2131-2142.
15. Topinkovà, E. Aging, disability and frailty. Ann. Nutr. Metab. 2008, 52, S6-S11.
16. Kalantar-Zadeh, K.; Block, G.; Horwich, T.; Fonarow, G.C. Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J. Am. Coll. Cardiol. 2004, 21, 1439-1444.
17. Kalantar-Zadeh, K.; Kilpatrick, R.D.; Kuwae, N. Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction. Nephrol. Dial. Transpl. 2005, 20, 1880-1888.
18. Kaysen, G.A.; Eiserich, J.P. The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. J. Am. Soc. Nephrol. 2004, 15, 538-548.
19. Lowrie, E.G.; Lew, N.L. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am. J. Kidney Dis. 1990, 15, 458-482
20. Reaich, D.; Price, S.R.; England, B.K.; Mitch, W.E. Mechanisms causing muscle loss in chronic renal failure. Am. J. Kidney Dis. 1995, 26, 242-247.
21. Khaw, K.T.; Dowsett, M.; Folkerd, E.; Bingham, S.; Wareham, N.; Luben, R.; Welch, A.; Day, N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007, 116, 2694-2701.
22. Kaisar, O.M.; Johnson, D.W.; Prins, J.B.; Isbel, N. The role of novel biomarkers of cardiovascular disease in chronic kidney disease: focus on adiponectin and leptin. Curr. Cardiol. Rev. 2008, 4, 287-292.
23. Axelsson, J.; Witasp, A.; Carrero, J.J.; Qureshi, A.R.; Suliman, M.E.; Heimbürger, O.; Bárány, P.; Lindholm, B.; Alvestrand, A.; Schalling, M. Circulating levels of visfatin/pre-B-cell colony-enhancing factor 1 in rekation to genotype, GFR, body composition, and survival in patients with CKD. Am. J. Kidney Dis. 2007, 49, 237-244.
24. Zoccali, C.; Mallamaci, F.; Tripepi, G.; Cutrupi, S.; Pizzini, P. Low triiodothyronine and survival in end-stage renal disease. Kidney Int. 2006, 70, 523-528.
25. Carrero, J.J.; Qureshi, A.R.; Axelsson, J.; Yilmaz, M.I.; Rehnmark, S.; Witt, M.R.; Barany, P.; Heimburger, O.; Suliman, M.E. et al. Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J. Int. Med. 2007, 262, 690-701.
26. Ikizler, T.A.; Wingard, R.L.; Harvell, J.; Shyr, Y.; Hakim, R. Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: A prospective study. Kidney Int. 1999, 55, 1945-1951.
27. Foley, R.N.; Pafrey, P.S.; Harnett, J.D.; Kent, G.M.; Murray, D.C. Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease. J. Am. Soc. Nephrol. 1996, 7, 728-736.
28. Chertow, G.M.; Goldstein-Fuchs, D.J.; Lazarus, J.M.; Kaysen, G.A. Prealbumin, mortality, and cause-specific hospitalization in hemodialysis patients. Kidney Int. 2005, 68, 2794-2800.
29. Keys, A.; Brozek, J.; Henschel, A.; Mickelsen, O.; Taylor, H. The Biology of Human Starvation, Minneapolis; University of Minnesota Press: Minneapolis, MN, USA, 1950.
30. Kopple, J.D.; Levey, A.S.; Greene, T.; Chumlea, W.C.; Gassman, J.J.; Hollinger, D.L.; Maroni, B.J.; Merrill, D.; Scherch, L.K.; Shulman, G. et al. Effect of dietary protein restriction on nutritional status in the modification of diet in renal diseases study. Kidney Int. 1997, 52, 778-791.
31. Aparicio, M.; Chauveau, P.; De Precigout, V.; Bouchet, J.L.; Lasseur, C.; Combe, C. Nutrition and outcome on renal replacement therapy of patients with chronic renal failure treated by a supplemented very low protein diet. J. Am. Soc. Nephrol. 2000, 11, 708-716.
32. Gil, H.W.; Yang, J.O.; Lee, E.Y.; Lee, E.M.; Choi, J.S.; Hong, S.Y. The effect of dialysis membrane flux on amino acid loss in haemodialysis patients. J. Korean Med. Sci. 2007, 22, 598-603.
33. Kario, K.; Matsuo, T.; Kobyasahi, H. Heparin cofactor II deficiency in elderly: Comparison with antithrombin II. Thromb. Res. 1992, 66, 489-498.
34. Joles, J.A.; Willekes-Koolschij, N.; Koomas, H.A. Hypoalbuminemia causes high blood pressure by increasing red cell lysophosphatidylcholine. Kidney Int. 1997, 52, 761-770.
35. Emerson, T.E. Unique features of albumin: A brief review. Crit. Care Med. 1989, 17, 690-694.
36. Bergstrom, J. Nutrition and mortality in hemodialysis. J. Am. Soc. Nephrol. 1995, 6, 1329-1341.
37. Nguyen-Khoa, T.; Massay, Z.A.; De Bandt, J.P.; Kebede, M.; Salama, L.; Lambrey, G.; Witko-Sarsat, V; Drüeke, T.B.; Lacour, B; Thévenin, M. Oxidative stress and haemodialysis: Role of inflammation and duration of dialysis treatment. Nephrol. Dial. Transpl. 2001, 16, 335-340.
38. Zoccali, C.; Mallamaci, F.; Asahia, K.; Benedetto, F.A.; Tripepi, G.; Tripepi, R.; Nicocia, G.; Buemi, M.; Miyata, T. Pentosidine, carotid atherosclerosis and alterations in left ventricular geometry in hemodialysis patients. J. Nephrol. 2001, 14, 293-298.
39. Koyama, H.; Nishizawa, Y. AGEs/RAGE in CKD: Irreversible metabolic memory road toward CVD? Eur. J. Clin. Invest. 2010, 40, 623-635.
40. Nakashima, A.; Carrero, J.J.; Qureshi, A.R.; Miyamoto, T.; Anderstam, B.; Barany, P.; Heimburger, O.; Stenvinkel, P.; Lindholm, B. Effect of circulating soluble receptor for Advanced glycation End products (sRAGE) and the proinflammatory RADE Ligand (EN-RAGE, S100A12) on mortality in hemodialysis patients. Clin. J. Am. Soc. Nephrol. 2010, 5, 2213-2219.
41. Zhou, L.L.; Hou, F.F.; Wang, G.B.; Yang, F.; Xie, D.; Wang, Y.P.; Tian, J.W. Accumulation of advanced oxidation protein products induces podocyte apoptosis and deletion through NADPH-dependent mechanisms. Kidney Int. 2009, 76, 1125-1127.
42. Witko-Sarsat, V.; Gausson, V.; Nguyen, A.T.; Touam, M.; Drüeke, T.; Santangelo, F.; Descamps-Latscha, B. AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target for N-acetylcysteine treatment in dialysis patients. Kidney Int. 2003, 64, 82-91.
43. Descamps-Latscha, B.; Witko-Sarsat, V.; Nguyen-Khoa, T.; Nguyen, A.T.; Gausson, V.; Mothu, N.; London, G.M.; Jungers, P. Advanced oxidation protein products as risk factors for cardiovascular events in nondiabetic predialysis patients. Am. J. Kidney Dis. 2005, 45, 39-47.
44. Valli, A.; Mohamed, E.S.; Meert, S.; Vanholder, R.; Lindholm, B.; Stenvinkel, P.; Watanabe, M.; Barany, P.; Alvestrand, A.; Anderstam, B. Overestimation of advanced oxidation protein products in uremic plasma due to presence of triglycerides and other endogenous factors. Clin. Chim. Acta 2007, 379, 87-94.
45. Panichi, V.; Migliori, M.; De Pietro, S.; Taccola, D.; Bianchi, A.M.; Giovannini, L.; Norpoth, M.; Metelli, M.R.; Cristofani, R.; Bertelli, A.A. et al. C-reactive protein and interleukin-6 levels are related to renal function in predialytic chronic renal failure. Nephron 2002, 91, 594-600.
46. Stenvinkel, P.; Haimburger, O.; Paultre, F.; Diczfalusy, U.; Wang, T.; Berglund, L.; Jogestrand, T. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999, 55, 1899-1911.
47. Yeun, J.Y.; Levine, R.A.; Mantadilok, V.; Kaysen, G.A. C-reactive protein predicts all-cause and cardiovascular mortality in haemodialysis patients. Am. J. Kidney Dis. 2000, 35, 469-476.
48. Eustace, J.A.; Astor, B.; Muntner, P.M.; Ikizler, T.A.; Coresh, J. Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. Kidney Int. 2004, 65, 1031-1040.
49. Schiffl, H.; Lang, S.M.; Stratakis, D.; Fischer, R. Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters. Nephrol. Dial. Transpl. 2001, 16, 1863-1869.
50. Cuneo, R.C.; Salomon, F.; Wiles, C.M.; Hesp, R.; Sönksen, P.H. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle and strength. J. Appl. Physiol. 1991, 70, 688-694.
51. Bistrian, B.R.; Schwartz, J.; Istifan, N.W. Cytokines, muscle proteolysis and the catabolic response to infection and inflammation. Proc. Soc. Exp. Boil. Med. 1992, 200, 220-223.
52. Zwaka, P.T.; Hombach, V.; Torzewski, J. C-reactive protein-mediated low-density lipoprotein uptake by macrophages. Circulation 2001, 103, 1194-1197.
53. Boeheme, M.; Kaehene, F.; Kuehne, A.; Bernhardt, W.; Shroder, M.; Pommer, W.; Fiscer, C.; Becker, H.; Muller, C.; Schindler, R. Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease. Nephrol. Dial. Transpl. 2007, 22, 2224-2229.
54. Tong, M.; Carrero, J.J.; Qureshi, A.R.; Anderstam, B.; Heimburger, O.; Barany, P.; Axelsson, J.; Alvestrand, A.; Stenvinkel, P.; Lindholm, B. et al. Plasma Pentraxin 3 in chronic kidney disease patients: Associations with renal function, protein-energy wasting, cardiovascular disease and mortality. Clin. J. Am. Soc. Nephrol. 2007, 2, 889-897.
55. Yilmaz, M.I.; Sonmez, A.; Ortiz, A.; Saglam, M.; kilic, S.; Eyileten, T.; Caglar, K.; Oguz, Y.; Vural, A.; Cakar, M. et al. Soluble TWEAK and PTX3 in nondialysis CKD patients: impact on endothelial Dysfunction and cardiovascular outcomes. Clin. J. Am. Soc. Nephrol. 2011, 6, 785-792.
56. Alberti, L.; Gilardini, L.; Zulian, A.; Micheletto, G.; Peri, G.; Doni, A.; Mantovani, A.; Invitti, C. Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors. Atherosclerosis 2009, 202, 455-460.
57. Raj, D.S.; Carrero, J.J.; Shah, V.O.; Qureshi, A.R.; Bárány, P.; Heimbürger, O.; Lindholm, B.; Ferguson, J.; Moseley, P.L.; Stenvinkel, P. Soluble CD14 levels, interleukin 6, and mortality among prevalent hemodialysis patiient. Am. J. Kidney Dis. 2009, 54, 1072-1080.
58. Shoji, T.; Shinohara, K.; Hatsuda, S.; Kimoto, E.; Fukumoto, S.; Emoto, M.; Tahara, H.; Koyama, H.; Ishimura, E.; Miki, T. et al. Altered relationship between body fat and plasma adiponectin in end-stage renal disease. Metabolism 2005, 54, 330-334.
59. Honda, H.; Qureshi, A.R.; Axelsson, J.; Heimburger, O.; Suliman, M.E.; Barany, P.; Stenvinkel, P.; Lindholm, B. Obese sarcopenia in patients with end-stage renal disease is associated with inflammation and increased mortality. Am. J. Clin. Nutr. 2007, 86, 633-638.
60. Kakiya, R.; Shoji, T.; Tsujimoto, Y.; Tatsumi, N.; Hatsuda, S.; Shinohara, K.; Kimoto, E.; Tahara, H.; Koyama, H.; Emoto, M. et al. Body fat mass and lean mass as predictors of survival in hemodialysis patients. Kidney Int. 2006, 70, 549-556.
61. Kalantar-Zadeh, K.; Kuwae, N.; Wu, D.Y.; Shantouf, R.S.; Fouque, D.; Anker, S.D.; Block, G.; Kopple, J.D. Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialysis patients. Am. J. Clin. Nutr. 2006, 83, 202-210.
62. Leinig, C.; Pecoits-Filho, R.; Nascimento, M.M.; Goncalves, S.; Riella, M.C.; Martins, C. Association between body mass index and body fat in chronic kidney disease stages 3 to 5, hemodialysis, and peritoneal dialysis patients. J. Ren. Nutr. 2008, 18, 424-429.
63. Carrero, J.J.; Cordeiro, A.C.; Lindholm, B.; Stenvinkel, P. the emerging pleiotrophic role of adipokines in the uremic phenotype. Curr. Opin. Nephrol. Hypertens. 2010, 19, 37-42.
64. Zoccali, C.; Postorino, M.; Marino, C.; Pizzini, P.; Cutrupi, S.; Tripepi, G. CREDIT working group abdominal obesity and all-cause mortality in end-stage renal disease. J. Am. Coll. Cardiol. 2009, 53, 1265-1272.
65. Knudson, J.D.; Payne, G.A.; Borbouse, L.; Tune, J.D. Leptin and mechanisms of endothelial dysfunction and cardiovascular disease. Curr. Hypertens. Rep. 2008, 10, 434-439.
66. Liu, S.W.; Qiao, S.B.; Yuan, J.S.; Liu, D.Q. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndrome(ACS) in humans. Clin. Endocrinol. 2009, 71, 202-207.
67. Schneiderman, J.; Simon, A.J.; Schroeter, M.R.; Flugelman, M.Y.; Konstantinides, S.; Schaefer, K. Leptin receptor is elevated in carotid plaques from neurologically symptomatic patients and positively correlated with augmented machrophage density. J. Vasc. Surg. 2008, 48, 1146-1155.
68. Dahl, T.B.; Yndestand, A.; Skjelland, M.; Oie, E.; Dahl, A.; Michelsen, A.; Damas, J.K.; Tunheim, S.H.; Ueland, T.; Smith, C. et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis. Possible role in inflammation and plaque destabilization. Circulation 2007, 115, 972-980.
69. Ramkumar, N.; Pappas, L.M.; Beddhu, S. Effect of body size and body composition on survival in peritoneal dialysis patients. Perit. Dial. Int. 2005, 25, 461-469.
70. Huang, C.X.; Tighiouart, H.; Beddhu, S.; Cheung, A.K.; Dwyer, J.T.; Eknoyan, G.; Beck, G.J.; Levey, A.S.; Sarnak, M.J. Both low muscle mass and low fat are associated with higher all-cause mortality in hemodialysis patients. Kidney Int. 2010, 77, 624-629.
71. Noori, N.; Kovesdy, C.P.; Dukkipati, R.; Kim, Y.; Duong, U.; Bross, R.; Oreopoulos, A.; Luna, A.; Benner, D.; Kopple, J.D. et al. Survival predictability of lean and fat mass in men and women undergoing maintenance hemodialysis. Am. J. Clin. Nut. 2010, 92, 1060-1070.
72. Tessari, P.; Deferrari, G.; Robaudo, C.; Vettore, M.; Pastorin, N.; De Biasi, L.; Garibotto, G.; Phenylalanine hydroxylation across the kidney in humans. Kidney Int. 1999, 56, 2168-2172.
73. Kopple, J.D. Phenylalanine and tyrosine metabolism in chronic kidney failure. J. Nutr. 2007, 137, 1586S-1590S.
74. Garibotto, G.; Sofia, A.; Saffioti, S.; Russo, R.; Deferrari, G.; Rossi, D.; Verzola, D.; Gandolfo, M.T.; Sala, M.R. Interorgan exchange of aminothiols in humans. Am. J. Physiol. Endocrinol. Metab. 2003, 284, E757-E763.
75. Soesters, P.B.; Deutz, N.E.; Fearon, K.C.; Dejong, C.H.; Renal metabolism of amino acids: Its role in inter-organ amino acid exchange. Am. J. Clin. Nutr. 2004, 79, 185-197.
76. Lee, M.E.; Wang, H. Homocysteine and hypomethylation: a novel link to vascular disease. Trends Cardiovasc. Med. 1999, 9, 49-54.
77. Cantoni, G.L. Experimental and clinical roles of S-Adenosylmethionine. In Biological Methylation and Drug Design; Borchardt, R.T., Creveling, C.R., Ueland, P.M., Eds.; Humana Press: Clifton, NJ, USA, 1986; pp. 227-238.
78. Liu, C.; Wang, Q.; Guo, H.; Xia, M.; Yuan, Q.; Hu, Y. Plasma S-adenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein E-deficient mice fed high dietary methionine. J. Nutr. 2008, 138, 311-315.
79. Valli, A.; Carrero, J.J.; Qureshi, A.R.; Garibotto, G.; Barany, P.; Axelsson, J.; Lindholm, B.; Stenvinkel, P.; Anderstam, B.; Suliman, M.E. Elevated serum levels of S-adenosylhomocysteine, but not homocysteine, are associated with cardiovascular disease in stage 5 chronic kidney disease patients. Clin. Chim. Acta 2008, 395, 106-110.
80. Ingrosso, D.; Cimmino, A.; Perna, A.F.; Masella, L.; De Santo, N.G.; De Bonis, M.L.; Vacca, M.; D'Esposito, M.; D'Urso, M.; Galletti, P. et al. Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 2003, 17, 1693-1694.
81. Baylis, C. Arginine, arginine analogous and nitric oxid production in chronic kidney disease. Nat. Clin. Pract. Nephrol. 2006, 2, 209-220.
82. Matsuoka, H. Endothelial dysfunction associated with oxidative stress in human. Diabetes Res. Clin. Pract. 2001, 54, S65-S72.
83. Kielstein, J.T.; Zoccali, C. Asymmetric dimethylarginine: A novel marker of risk and potential target for therapy in chronic kidney disease. Curr. Opin. Nephrol. Hyperten. 2008, 17, 609-615.
84. Vallance, P.; Leone, A.; Calver, A.; Collier, J.; Moncada, S. Accumulation of an endogenous inhibitor on nitric oxide synthesis in chronic renal failure. Lancet 1992, 339, 572-575.
85. Mihout, F.; Shweke, N.; Bigé, N.; Jouanneau, C.; Dussaule, J.C.; Ronco, P.; Chatziantoniou, C.; Boffa, J.J. Asymmetric dimethylarginine (ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF-β1 synthesis. J. Pathol. 2011, 223, 37-45.
86. Cross, J.M.; Donald, A.; Vallance, P.; Deanfield, J.E.; Woolfson, R.G.; MacAllister, R.J. Hemodialysis improves endothelial function in humans. Nephrol. Dial. Transpl. 2001 16, 1823-1829.
87. Kaskel, F. Chronic renal disease: A growing problem. Kidney Int. 2003, 64, 1141-1151.
88. Qing, D.P.; Ding, H.U.; Vagdama, J. Elevated myocardial cytosolic calcium impairs insulin-like growth factor-1 stimlated protein synthesis in chronic renal failure. J. Am. Soc. Nephrol. 1999, 10, 84-91.
89. Blum, W.F.; Ranke, M.B.; Kietzmann, K.; Tönshoff, B.; Mehls, O. Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uremia. Pediatr. Nephrol. 1991, 5, 539-544.
90. Sun, D.F.; Zheng, Z.; Tummala, P.; Oh, J.; Schaefer, F.; Rabkin, R. Chronic uremia attenuates growth hormone-induced signal transduction in skeletal muscle. J. Am. Soc. Nephrol. 2004, 15, 2630-2646.
91. Chen, Y.; Biada, J.; Sood, S.; Rabkin, R. Uremia attenuates growth hormone-stimulated insulin-like growth factor-1 expression, a process worsened by inflammation. Kidney Int. 2010, 78, 89-95.
92. Cooney, R.N.; Shumate, M. The inhibitory effects of interleukin-1 on growth hormone action during catabolic illness. Vitam. Horm. 2006, 74, 317-340.
93. Brungger, M.; Hulter, H.N.; Krapf, R. Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone insensitivity in humans. Kidney Int. 1997, 51, 216-221.
94. Garibotto, G.; Russo, R.; Sofia, A.; Ferone, D.; Fiorini, F.; Cappelli, V.; Tarroni, A.; Gandolfo, M.T.; Vigo, E.; Valli, A. et al. Effects of uremia and inflammation on growth hormone resistance in patients with chronic kidney disease. Kidney Int. 2008, 74, 937-945.
95. Bhasin, S.; Taylor, W.E.; Singh, R.; Artaza, J.; Sinha-Hikim, I.; Jasuja, R.; Choi, H.; Gonzalez-Cadavid, N.F. The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. J. Gerontol. Med. Sci. 2003, 58, 1103-1110.
96. Wolfe, R.; Ferrando, A.; Sheffield-Moore, M.; Urban, R. Testosterone and muscle protein metabolism. Mayo Clin. Proc. 2000, 75, S55-S59.
97. Harman, S.M.; Metter, E.J.; Tobin, J.D.; Pearson, J.; Blackman, M.R. Baltimore longitudinal study of aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J. Clin. Endocrinol. Metab. 2001, 86, 724-731.
98. Morley, J.E.; Melmed, S. Gonadal dysfunction in systemic disorders. Metabolism 1979, 28, 1051-1073.
99. Roubenoff, R.; Parise, H.; Payette, H.A.; Abad, L.W.; D'Agostino, R.; Jacques, P.F.; Wilson, P.W.; Dinarello, C.A.; Harris, T.B. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old communitydwelling men and women: the Framingham Heart Study. Am. J. Med. 2003, 115, 429-435.
100. Haring, R.; Nauck, M.; Volzke, H.; Endlich, K., Lendeckel, U.; Friedrich, N.; Dorr, M.; Rettig, R.; Kroemer, H.K.; Wallaschofski, H. Low serum testosterore is associated with increased mortality in men with stage 3 or greater nephropathy. Am. J. Nephrol. 2011, 33, 209-217.
101. Khaw, K.T.; Dowsett, M.; Folkerd, E.; Bingham, S.; Wareham, N.; Luben, R.; Welch, A.; Day, N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) prospective population study. Circulation 2007, 116, 2694-2701.
102. Carrero, J.J.; Qureshi, A.R.; Parini, P.; Arver, S.; Lindholm, B.; Bárány, P.; Heimbürger, O.; Stenvinkel, P. Low serum testosterone increases mortality risk among male dialysis patients. J. Am. Soc. Nephrol. 2009, 20, 613-620.
103. Gungor, O.; Kircelli, F.; Carrero, J.J.; Asci, G.; Toz, H.; Tatar, E.; Hur, E.; Sever, M.S.; Arinsoy, T.; Ok, E. Endogenous testosterone and mortality in male hemodialysis patients: Is this the resul of aging? Clin. J. Am. Soc. Nephrol. 2010, 5, 2018-2023.
104. Alvestrand, A.; DeFronzo, R.A.; Smith, D.; Wahren, J. Influence of Hyperinsulinemia on intracellular amino acids levels and amino acid exchange across splanchnic and leg tissues in uremia. Clin. Sci. 1988, 74, 155-162.
105. Bailey, J.L.; Zheng, B.; Hu, Z.; Price, S.R.; Mitch, W.E. Chronic kidney disease causes defects in signalling through the insulin receptor substrate/phosphatidylinositol 3-kinase/Akt pathway: Implications for muscle atrophy. J. Am. Soc. Nephrol. 2006, 17, 1388-1394.
106. Pupim, L.B.; Flakoll, P.J.; Majchrzak, K.M.; Aftab Guy, D.L.; Stenvinkel, P.; Ikizler, T.A. Increased muscle protein breakdown in chronic hemodialysis patients with type 2 diabetes mellitus. Kidney Int. 2005, 68, 1857-1865.
107. Rajan, V.; Mitch, W.E. Ubiquitin, proteasomes and proteolytic mechanisms activated by kidney disease. Biochim. Biophys. Acta 2008, 1782, 795-799.
108. Reaich, D.; Channo, S.M.; Scrimgeour, C.M.; Daley, S.E.; Wilkinson, R.; Goodship, T.H. Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation. Am. J. Physiol. 1993, 265, E230-E235.
109. Burrowes, J.D.; Larive, B.; Chertow, G.M. Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the haemodialysis (HEMO) study. Nephrol. Dial. Transpl. 2005, 20, 2765-2774.
110. Cheung, W.; Yu, P.X.; Little, B.M. Role of leptin and melanocortin signaling in uremia-associated cachexia. J. Clin. Invest. 2005, 115, 1659-1665.
111. Kalantar Zadeh, K.; Block, G.; Mc Allister, C.J.; Humphreys, M.H.; Kopple, J.D. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am. J. Clin. Nutr. 2004, 80, 299-307.
112. Carrero, J.J.; Qureshi, A.R.; Axelsson, J.; Avesani, C.M.; Suliman, M.E.; Kato, S.; Bárány, P.; Snaedal-Jonsdottir, S.; Alvestrand, A.; Heimbürger, O. et al. Comparison of nutritional and inflammatory markers in dialysis patients with reduced appetite. Am. J. Clin. Nutr. 2007, 85, 695-701.
113. Gayle, D.A.; Desai, M.; Casillas, E.; Belooseski, R.; Ross, M.G. Gender specific orexigenic and anorexigenic mechanisms in rats. Life Sci. 2006, 79, 1531-1536.
114. Latos, D.L. Chronic dialysis in patients over age 65. J. Am. Soc. Nephrol. 1996, 7, 637-646.
115. Lindeman, R.D. Overview: Renal physiology and pathophysiology of aging. Am. J. Kidney Dis. 1990, 16, 275-282.
116. Timiras, P.S. Aging of the Skeleton, Joints and Muscles. In Physiological Basis of Aging and Geriatrics, 2nd ed.; Timiras, P.D., Ed.; CRC Press: Boca Raton, FL, USA, 1994; pp. 259-272.
117. Rothstein, M. Altered proteins, errors and aging. In Protein Metabolism in Aging; Segal, H.L., Rothstein, M., Bergamini, P., Eds.; Wiley-Liss Inc.: New York, NY, USA, 1990; pp. 3-14.
118. Gersovitz, M.; Bier, D.; Matthews, D.; Udall, J.; Munro, H.N.; Young, V.R. Dynamic aspects of whole body glycine metabolism. Influence of protein intake in young adult and elderly males. Metabolism 1980, 29, 1087-1094.
119. Robert, J.J.; Bier, D.; Schoeller, D.; Wolfe, R.; Matthews, D.E.; Munro, H.N.; Young, V.R. Effect of intravenous glucose on whole body leucine dynamics, studied with 1-13C-leucine, in healthy, young and elderly adults. J. Gerontol. 1984, 39, 673-681.
120. Nair, K.S. Age-related changes in muscle. Mayo. Clin. Proc. 2000, 75S, S14-S18.
121. Boirie, Y.; Gachon, P.; Cordat, N.; Ritz, P.; Beaufrère, B. Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women. J. Clin. Endocrinol. Metab. 2001, 86, 638-644.
122. Oreopoulos, A.; Kalantar-Zadeh, K.; Sharma, A.M.; Fonarow, G.C. The obesity paradox in the elderly: Potential mechanisms and clinical implications. Clin. Geriatr. Med. 2009, 25, 643-659.
123. Miller, S.L.; Wolfe, R.R. The danger of weight loss in the elderly. J. Nutr. Health Aging. 2008, 12, 487-489.
124. Vanholder, R.; Ringoir, S. Infectious morbidity and defects of phagocytic function in end-stage renal disease: A review. J. Am. Soc. Nephrol. 1993, 3, 1541-1554.
125. Dalrymple, L.S.; Go, A.S. Epidemiology of acute infections among patients with chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2008, 3, 1487-1493.
126. Allon, M.; Depner, T.A.; Radeva, M.; Bailey, J.; Beddhu, S.; Butterly, D.; Coyne, D.W.; Gassman, J.J.; Kaufman, A.M.; Kaysen, G.A. et al. Impact of dialysis dose and membrane on infection-related hospitalization and death: Results of the HEMO Study. J. Am. Soc. Nephrol. 2003, 14, 1863-1870.
127. Chinen, J.; Shearer, W.T. Secondary immunodeficiencies, including HIV infection. J. Allergy Clin. Immunol. 2008, 121, S388-392.
128. Hulsewe, K.W.; van Acker, B.A.; Von Meyenfeldt, M.F.; Soeters, P.B. Nutritional depletion and dietary manipulation: Effects on the immune response. World J. Surg. 1999, 23, 536-544.
129. Souba, W.W. Nutritional support. N. Engl. J. Med. 1997, 336, 41-48.
130. Alexander, J.W. Immunoenhancement via enteral nutrition. Arch. Surg. 1993, 128, 1242-1245.
131. Kimmel, P.L.; Phillips, T.M.; Lew, S.Q.; Langman, C.B. Zinc modulates mononuclear cellular calcitriol metabolism in peritoneal dialysis patients. Kidney Int. 1996, 49, 1407-1412.
132. Erten, Y.; Kayatas, M.; Sezer, S.; Kayataş, M.; Haberal, A.; Güz, G.; Erten, Y.; Hizel, N.; Boyaciog̈lu, S.; Gülmüş, S. et al. Zinc deficiency: Prevalence and causes in hemodialysis patients and effect on cellular immune response. Transpl. Proc. 1998, 30, 850-851.
133. Casciato, D.A.; McAdam, L.P.; Kopple, J.D.; Bluestone, R.; Goldberg, L.S.; Clements, P.J.; Knutson, D.W. Immunologic abnormalities in hemodialysis patients: Improvement after pyridoxine therapy. Nephron 1984, 38, 9-16.
134. Dobbelstein, H.; Korner, W.F.; Mempel, W.; Grosse-Wilde, H.; Edel, H.H. Vitamin B6 deficiency in uremia and its implications for the depression of immune responses. Kidney Int. 1974, 5, 233-239.
135. Minnaganti, V.R.; Cunha, B.A. Infections associated with uremia and dialysis. Infect. Dis. Clin. North Am. 2001, 15, 385-406.
136. Cohen, G.; Haag-Weber, M.; Horl, W.H. Immune dysfunction in uremia. Kidney Int. Supp. 1997, 62, S79-S82.
137. Pesanti, E.L. Immunologic defects and vaccination in patients with chronic renal failure. Infect. Dis. Clin. North Am. 2001, 15, 813-832.
138. Eleftheriadis, T.; Antoniadi, G.; Liakopoulos, V.; Kartsios, C.; Stefanidis, I. Disturbances of acquired immunity in hemodialysis patients. Semin. Dial. 2007, 20, 440-451.
139. Lim, W.H.; Kireta, S.; Leedham, E.; Russ, G.R.; Coates, P.T. Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. Kidney Int. 2007, 72, 1138-1148.
140. Fantuzzi, G.; Faggioni, R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J. Leukoc. Biol. 2000, 68, 437-446.
141. Matarese, G.; La Cava, A.; Sanna, V.; Lord, G.M.; Lechler, R.I.; Fontana, S.; Zappacosta, S. Balancing susceptibility to infection and autoimmunity: A role for leptin? Trends Immunol. 2002, 23, 182-187.
142. Madej, T.; Boguski, M.S.; Bryant, S.H. Threading analysis suggests that the obese gene product may be a helical cytokine. FEBS Lett. 1995, 373, 13-18.
143. Baumann, H.; Morella, K.K.; White, D.W.; Dembski, M.; Bailon, P.S.; Kim, H.; Lai, C.F.; Tartaglia, L.A. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. USA 1996, 93, 8374-8378.
144. Lord, G.M.; Matarese, G.; Howard, J.K.; Baker, R.J.; Bloom, S.R.; Lechler, R.I. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998, 394, 897-901.
145. Loffreda, S.; Yang, S.Q.; Lin, H.Z.; Karp, C.L.; Brengman, M.L.; Wang, D.J.; Klein, A.S.; Bulkley, G.B.; Bao, C.; Noble, P.W.; Lane, M.D.; Diehl, A.M. Leptin regulates proinflammatory immune responses. FASEB J. 1998, 12, 57-65.
146. Gabay, C.; Dreyer, M.G.; Pellegrinelli, N.; Chicheportiche, R.; Meier, C.A. Leptin directly induces the secretion of interleukin 1 receptor antagonist in human monocytes. Clin. Endocrinol. Metab. 2001, 86, 783-791.
147. Santos-Alvarez, J.; Goberna, R.; Sanchez-Margalet, V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol. 1999, 194, 6-11.
148. Sanchez-Margalet, V.; Martin-Romero, C.; Santos-Alvarez, J.; Goberna, R.; Najib, S.; Gonzalez-Yanes, C. Role of leptin as an immunomodulator of blood mononuclear cells: Mechanism of action. Clin. Exp. Immunol. 2003, 133, 11-19.
149. Matarese, G.; La Cava, A. The intricate interface between immune system and metabolism. Trends Immunol. 2004, 25, 193-200.
150. Rajala, M.W.; Scherer, P.E. The adipocyte. At the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003, 144, 3765-3773.
151. Diez, J.J.; Iglesias, P.; Fernandez-Reyes, M.J.; Aguilera, A.; Bajo, M.A.; Alvarez-Fidalgo, P.; Codoceo, R.; Selgas, R. Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease. Clin. Endocrinol. 2005, 62, 242-249.
152. McTernan, P.G.; Fisher, F.M.; Valsamakis, G.; Chetty, R.; Harte, A.; McTernan, C.L.; Clark, P.M.; Smith, S.A.; Barnett, A.H.; Kumar, S. Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J. Clin. Endocrinol. Metab. 2003, 88, 6098-6106.
153. Cohen, G.; Ilic, D.; Raupachova, J.; Hörl W.H. Resistin inhibits essential functions of polymorphonuclear leukocytes. J. Immunol. 2008, 181, 3761-3768.
154. Lim, V.S.; Kopple, J.D. Protein metabolism in patients with chronic renal failure: Role of uremia and dialysis. Kidney Int. 2000, 58, 1-10.
155. Mitch, W.E. Malnutrition: A frequent misdiagnosis for hemodialysis patients. J. Clin. Invest. 2002, 110, 437-439.
156. Stevinkel, P.; Heimburger, O.; Lindholm, B. Wasting, but not malnutrition, predicts cardiovascular mortality in end-stage renal disease. Nephrol. Dial. Transpl. 2004, 19, 2181-2183.
157. Mitch, W.E.; Goldberg, A.L. Mechanisms of muscle wasting: The role of ubiquitin-proteasome system. N. Engl. J. Med. 1996, 335, 1897-1905.
158. Lecker, S.H.; Goldberg, A.L.; Mitch, W.E. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J. Am. Soc. Nephrol. 2006, 17, 1807-1819.
159. Dupont-Versteegden, E.E. Apoptosis in skeletal muscle and its relevance to atrophy. World J. Gastroenterol. 2006, 12, 7463-7466.
160. Gundersen, K.; Bruusgaard, J.C. Nuclear domains during muscle atrophy: Nuclei lost or paradigm lost? J. Physiol. 2008, 586, 2675-2681.
161. Frost, R.A.; Lang, C.H. Protein kinase B/Akt: A nexus of growth factor and cytokine signaling in determining muscle mass. J. Appl. Physiol. 2007, 103, 378-387.
162. Yamaguchi, H.; Wang, H.G. The protein kinase PKB/Akt regulates cell servival and apoptosis by inhibiting Bax conformational change. Oncogene 2001, 20, 7779-7786.
163. Lee, S.W.; Dai, G.; Hu, Z.; Wang, X.; Du, J.; Mitch, W.E. Regulation of muscle protein degradation: Coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidynositol 3 kinase. J. Am. Soc. Nephrol. 2004, 15, 1537-1545.
164. Zhang, L.; Wang, X.H.; Wang, H.; Du, J.; Mitch, W.E. Satellite cell dysfunction and impaired IGF-I signaling cause CKD-induced muscle atrophy. J. Am. Soc. Nephrol. 2010, 21, 419-427.
165. Zhang, L.; Ran, L.; Garcia, G.E.; Wang, X.H.; Han, S.; Du, J.; Mitch, W.E. Chemokine CXCL16 regulates neutrophil and macrophage infiltration into injured muscle promoting muscle regeneration. Am. J. Pathol. 2009, 175, 2518-2527.
166. Verzola, D.; Procopio, V.; Sofia, A.; Villaggio B.; Tarroni, A.; Bonanni, A.; Mannucci, I.; De Cian, F.; Gianetta, E.; Saffioti, S.; Garibotto, G. Apoptosis and myostatin mRNA are upregulated in skeletal muscle of patients with chronic kidney disease. Kidney Int. 2011, 79, 773-782.
167. Garibotto, G.; Russo, R.; Sofia, A.; Sala, M.R.; Robaudo, C.; Moscatelli, P.; Deferrari, G.; Tizianello, A. Skeletal muscle protein synthesis and degradation in patients with chronic renal failure. Kidney Int. 1994, 45, 1432-1439.
168. Hara, Y.; May, R.C.; Kelly, R.A.; Mitch, W.E. Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats. Kidney Int. 1987, 32, 808-814.
169. Reaich, D.; Channon, S.M.; Scrimgeour, C.M.; Daley, S.E., Wilkinson, R.; Goodship, T.H. Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation. Am. J. Physiol. 1993, 265, E230-E235.
170. Young, G.A.; Swanepoel, C.R.; Croft, M.R.; Hobson, S.M.; Parsons, F.M. Anthropometry and plasma valine, amino acids, and proteins in the nutritional assessment of hemodialysis patients. Kidney Int. 1982, 21, 492-499.
171. Kornasion, R.; Riederer, I.; Butler-Browne, G.; Mouly, V.; Uni, Z.; Halevy, O. Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways. Biochim. Biophys. Acta 2009, 1793, 755-763.