American Journal of Kidney Diseases
Symposium Proceedings: Improving Prognosis for Kidney Disorders in the 21st Century: Hypertension, Anemia, Nutrition, and Lipids| Volume 38, ISSUE 6, P1343-1350, December 01, 2001

Relative contributions of nutrition and inflammation to clinical outcome in dialysis patients


      Protein-energy malnutrition (PEM) is a common phenomenon in maintenance dialysis (MD) patients and a risk factor for poor quality of life and increased morbidity and mortality, including cardiovascular death, in these individuals. The association between undernutrition and adverse outcome in MD patients, which stands in contrast to that seen in the general population, has been referred to as reverse epidemiology. Measures of food intake, body composition tools, nutritional scoring systems, and laboratory values are used to assess the degree of severity of PEM, but no uniform approach is available for rating the overall severity of PEM. Epidemiologic studies suggest that inflammation is a missing link between PEM and poor clinical outcome in MD patients, and the existence of a malnutrition inflammation complex syndrome is suggested in these patients. Inflammation may be due to subclinical and clinically apparent illnesses. Some investigators suggest that PEM may predispose to illness and inflammation. There is a paucity of information concerning the effect of nutritional therapy on morbidity and mortality in MD patients. Interventional studies of the effect of nutritional support on outcome often are difficult to interpret because of small sample sizes, short duration of study, and other limitations. Large-scale, randomized, clinical trials of the effects of nutritional intake, nutritional status, and inflammation on clinical outcome are needed to define better the relationships between these factors in MD patients. © 2001 by the National Kidney Foundation, Inc.


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        • Renal Data System US
        USRD 2000 Annual Data Report: Atlas of End Stage Renal Diseases in the United States.
        National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2000
      1. Kalantar-Zadeh K, Kopple JD, Block G, Humphries MH: Association between SF36 quality of life measures and nutrition, hospitalization and mortality in hemodialysis. J Am Soc Nephrol (in press)

        • Nicolucci A
        • Procaccini DA
        Why do we need outcomes research in end stage renal disease?.
        J Nephrol. 2000; 13: 401-404
        • Kopple JD
        Nutritional status as a predictor of morbidity and mortality in maintenance dialysis patients.
        ASAIO J. 1997; 43: 246-250
        • Mehrotra R
        • Kopple JD
        Nutritional management of maintenance dialysis patients: Why aren't we doing better?.
        Annu Rev Nutr. 2001; 21: 343-379
        • Kopple JD
        • Zhu X
        • Lew NL
        • Lowrie EG
        Body weight-for-height relationships predict mortality in maintenance hemodialysis patients.
        Kidney Int. 1999; 56: 1136-1148
        • Lowrie EG
        • Lew NL
        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
        • Coresh J
        • Longenecker JC
        • Miller ER
        • Young HJ
        • Klag MJ
        Epidemiology of cardiovascular risk factors in chronic renal disease.
        J Am Soc Nephrol. 1998; 9: S24-S30
        • Zager PG
        • Nikolic J
        • Brown RH
        • Campbell MA
        • Hunt WC
        • Peterson D
        • Van Stone J
        • Levey A
        • Meyer KB
        • Klag MJ
        • Johnson HK
        • Clark E
        • Sadler JH
        • Teredesai P
        “U” curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc.
        Kidney Int. 1998; 54: 561-569
        • Kaysen GA
        Malnutrition and the acute-phase reaction in dialysis patients—how to measure and how to distinguish.
        Nephrol Dial Transplant. 2000; 15: 1521-1524
        • Bergstrom J
        • Lindholm B
        • Lacson Jr, E
        • Owen Jr, W
        • Lowrie EG
        • Glassock RJ
        • Ikizler TA
        • Wessels FJ
        • Moldawer LL
        • Wanner C
        • Zimmermann J
        What are the causes and consequences of the chronic inflammatory state in chronic dialysis patients?.
        Semin Dial. 2000; 13: 163-175
        • Zimmermann J
        • Herrlinger S
        • Pruy A
        • Metzger T
        • Wanner C
        Inflammation enhances cardiovascular risk and mortality in hemodialysis patients.
        Kidney. 1999; 55: 648-658
        • Yeun JY
        • Levine RA
        • Mantadilok V
        • Kaysen GA
        C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients.
        Am J Kidney Dis. 2000; 35: 469-476
        • Kalantar-Zadeh K
        • Kleiner M
        • Dunne E
        • Ahern K
        • Nelson M
        • Koslowe R
        • Luft FC
        Total iron-binding capacity-estimated transferrin correlates with the nutritional subjective global assessment in hemodialysis patients.
        Am J Kidney Dis. 1998; 3: 263-272
        • Grodstein GP
        • Blumenkrantz MJ
        • Kopple JD
        Nutritional and metabolic response to catabolic stress in uremia.
        Am J Clin Nutr. 1980; 33: 1411-1416
        • Borah MF
        • Schoenfeld PY
        • Gotch FA
        • Sargent JA
        • Wolfsen M
        • Humphreys MH
        Nitrogen balance during intermittent dialysis therapy of uremia.
        Kidney Int. 1978; 14: 491-500
        • Chertow GM
        • Lazarus JM
        Malnutrition as a risk factor for morbidity and mortality in maintenace dialysis patients.
        in: Nutritional Management of Renal Disease. Williams & Wilkins, Baltimore, MD1997: 257-276
        • Kalantar-Zadeh K
        • Lehn RS
        • McAllister CJ
        • Kopple JD
        Normalized protein nitrogen appearance is correlated with hospitalization and mortality in hemodialysis patients with Kt/V >1.20.
        J Am Soc Nephrol. 2001; 12 (abstr): 215A
      2. Kalantar-Zadeh K, Kopple JD, Deepak S, Block B, Block G: Food intake characteristics of the dialysis patients as obtained by food frequency questionnaire. J Renal Nutr (in press)

        • Clermont G
        • Lecour S
        • Lahet J
        • Siohan P
        • Vergely C
        • Chevet D
        • Rifle G
        • Rochette L
        Alteration in plasma antioxidant capacities in chronic renal failure and hemodialysis patients: A possible explanation for the increased cardiovascular risk in these patients.
        Cardiovasc Res. 2000; 47: 618-623
        • Becker AE
        • de Boer OJ
        • van Der Wal AC
        The role of inflammation and infection in coronary artery disease.
        Annu Rev Med. 2001; 52: 289-297
        • Kaplan NM
        Risk factor for atherosclerotic disease.
        in: ed 6. Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine. Saunders, Philadelphia, PA2001: 1010-1039
        • Kaysen GA
        C-reactive protein: A story half told.
        Semin Dial. 2000; 13: 143-146
        • Yeun JY
        • Levine RA
        • Mantadilok V
        • Kaysen GA
        C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients.
        Am J Kidney Dis. 2000; 35: 469-476
        • Bergstrom J
        • Wang T
        • Lindholm B
        Factors contributing to catabolism in end-stage renal disease patients.
        Miner Electrolyte Metab. 1998; 24: 92-101
        • Foley RN
        • Parfrey PS
        • Harnett JD
        • Kent GM
        • Murray DC
        • Barre PE
        Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.
        J Am Soc Nephrol. 1996; 7: 728-736
        • Grodstein GP
        • Blumenkrantz MJ
        • Kopple JD
        Nutritional and metabolic response to catabolic stress in chronic uremia.
        Am J Clin Nutr. 1980; 33: 1411
        • Keane WF
        • Collins AJ
        Influence of co-morbidity on mortality and morbidity in patients treated with hemodialysis.
        Am J Kidney Dis. 1994; 24: 1010-1018
        • Kaysen GA
        • Dubin JA
        • Muller HG
        • Rosales LM
        • Levin NW
        The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients. The HEMO Study Group.
        Kidney Int. 2000; 58: 346-352
        • Panichi V
        • Migliori M
        • De Pietro S
        • Taccola D
        • Andreini B
        • Metelli MR
        • Giovannini L
        • Palla R
        The link of biocompatibility to cytokine production.
        Kidney Int. 2000; 58: S96-S103
        • Ikizler TA
        • Wingard RL
        • Harvell J
        • Shyr Y
        • Hakim RM
        Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: A prospective study.
        Kidney Int. 1999; 55: 1945-1951
        • Iseki K
        • Tozawa M
        • Yoshi S
        • Fukiyama K
        Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients.
        Nephrol Dial Transplant. 1999; 14: 1956-1960
        • Bergstrom J
        • Lindholm B
        Malnutrition, cardiac disease, and mortality: An integrated point of view.
        Am J Kidney Dis. 1998; 32: 834-841
        • Flores EA
        • Bistrian BR
        • Pomposelli J
        • Dinarello CA
        • Blackburn GL
        Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat: A synergistic effect with interleukin 1.
        J Clin Invest. 1989; 83: 1614-1622
        • McCarthy DO
        Tumor necrosis factor alpha and interleukin-6 have differential effects on food intake and gastric emptying in fasted rats.
        Res Nurs Health. 2000; 23: 222-228
        • Witko-Sarsat V
        • Friedlander M
        • Nguyen Khoa T
        • Capeillere-Blandin C
        • Nguyen AT
        • Canteloup S
        • Dayer JM
        • Jungers P
        • Drueke T
        • Descamps-Latscha B
        Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure.
        J Immunol. 1998; 161: 2524-2532
        • Kaysen GA
        • Stevenson FT
        • Depner TA
        Determinants of albumin concentration in hemodialysis patients.
        Am J Kidney Dis. 1997; 29: 658-668
        • Gunnell J
        • Yeun JY
        • Depner TA
        • Kaysen GA
        Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients.
        Am J Kidney Dis. 1999; 33: 63-72
        • Barany P
        • Divino Filho JC
        • Bergstrom J
        High C-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients.
        Am J Kidney Dis. 1997; 29: 565-568
        • Kalantar-Zadeh K
        • Don BR
        • Rodriguez RA
        • Humphreys MH
        Serum ferritin is a marker of morbidity and mortality in hemodialysis patients.
        Am J Kidney Dis. 2001; 37: 564-572
        • Kalantar-Zadeh K
        • Kopple JD
        • Block G
        • Humphreys MH
        A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.
        Am J Kidney Dis. 2001; 38: 1251-1263
        • Kalantar-Zadeh K
        • Kleiner M
        • Dunne E
        • Lee GH
        • Luft FC
        A modified quantitative subjective global assessment of nutrition for dialysis patients.
        Nephrol Dial Transplant. 1999; 14: 1732-1738
        • Canada-USA Peritoneal Dialysis Study Group
        Adequacy of dialysis and nutrition in continuous peritoneal dialysis: Association with clinical outcomes.
        J Am Soc Nephrol. 1996; 7: 198-207
        • Beto JA
        • Bansal VK
        • Hart J
        • McCarthy M
        • Roberts D
        Hemodialysis prognostic nutrition index as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. Council on Renal Nutrition National Research Question Collaborative Study Group.
        J Ren Nutr. 1999; 9: 2-8
        • Kalantar-Zadeh K
        • Block G
        • Kelly MP
        • Schroepfer C
        • Rodriguez RA
        • Humphreys MH
        Near infra-red interactance for longitudinal assessment of nutrition in dialysis patients.
        J Ren Nutr. 2001; 11: 23-31
        • Stenvinkel P
        • Heimburger O
        • Lindholm B
        • Kaysen GA
        • Bergstrom J
        Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome).
        Nephrol Dial Transplant. 2000; 15: 953-960
        • Qureshi AR
        • Alvestrand A
        • Danielsson A
        • Divino-Filho JC
        • Gutierrez A
        Factors predicting malnutrition in hemodialysis patients: A cross-sectional study.
        Kidney Int. 1998; 53: 773-782
        • Souba WW
        Nutritional support.
        N Engl J Med. 1997; 336: 41-48
        • Leon JB
        • Majerle AD
        • Soinski JA
        • Kushner I
        • Ohri-Vachaspati P
        • Sehgal AR
        Can a nutrition intervention improve albumin levels among hemodialysis patients? A pilot study.
        J Ren Nutr. 2001; 11: 9-15
        • Koretz RL
        Does nutritional intervention in protein-energy malnutrition improve morbidity or mortality?.
        J Ren Nutr. 1999; 9: 119-121
        • Keys A
        • Brozek J
        • Henschel A
        • Mickelsen O
        • Longstreet Taylor H
        The Biology of Human Starvation. Vol I. The University of Minnesota Press, St. Paul, MN1950
        • Ginn H
        • Frost A
        • Lacy W
        Nitrogen balance in hemodialysis patients.
        Am J Clin Nutr. 1968; 21: 385-393
        • Hulsewe KW
        • van Acker BA
        • von Meyenfeldt MF
        • Soeters PB
        Nutritional depletion and dietary manipulation: Effects on the immune response.
        World J Surg. 1999; 23: 536-544
        • Alexander JW
        Immunoenhancement via enteral nutrition.
        Arch Surg. 1993; 128: 1242-1245
        • De Simone C
        • Tzantzoglou S
        • Famularo G
        • Moretti S
        • Paoletti F
        • Vullo V
        • Delia S
        High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients.
        Immunopharmacol Immunotoxicol. 1993; 15: 1-12
        • De Simone C
        • Famularo G
        • Tzantzoglou S
        • Trinchieri V
        • Moretti S
        • Sorice F
        Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: Effect of oral L-carnitine.
        AIDS. 1994; 8: 655-660
        • Guo SS
        • Siervogel RM
        • Chumlea WC
        Epidemiological applications of body composition: The effects and adjustment of measurement errors.
        Ann N Y Acad Sci. 2000; 904: 312-316
        • Holford TR
        • Stack C
        Study design for epidemiologic studies with measurement error.
        Stat Methods Med Res. 1995; 4: 339-358
        • Vonesh EF
        • Schaubel DE
        • Hao W
        • Collins AJ
        Statistical methods for comparing mortality among ESRD patients: Examples of regional/international variations.
        Kidney Int. 2000; 57: 19-27
        • Kopple JD
        The nutrition management of the patient with acute renal failure.
        JPEN J Parenter Enteral Nutr. 1996; 20: 3-12
        • Kuhlmann MK
        • Schmidt F
        • Kohler H
        High protein/energy vs. standard protein/energy nutritional regimen in the treatment of malnourished hemodialysis patients.
        Miner Electrolyte Metab. 1999; 25: 306-310
        • Chertow GM
        • Ling J
        • Lew NL
        • Lazarus JM
        • Lowrie EG
        The association of intradialytic parenteral nutrition administration with survival in hemodialysis patients.
        Am J Kidney Dis. 1994; 24: 912-920
        • Capelli JP
        • Kushner H
        • Camiscioli TC
        • Chen SM
        • Torres MA
        Effect of intradialytic parenteral nutrition on mortality rates in end-stage renal disease care.
        Am J Kidney Dis. 1994; 23: 808-816
        • Wolfson M
        • Foulks CJ
        Intradialytic parenteral nutrition: A useful therapy?.
        Nutr Clin Pract. 1996; 11: 5-11