**8. References**

306 Progress in Hemodialysis – From Emergent Biotechnology to Clinical Practice

malnutrition enhanced by inflammation may overcome the long-term impact of traditional risk factors for CVD and may cause the HP patients to not live long enough to develop elevated levels of cholesterol causing them die sooner than is expected. Also, evidence suggests that lipid levels become more elevated and more strongly associated with CVD the longer the HP receives dialysis and suggests that even though counter-intuitive cholesterol findings are evident in early dialysis traditional therapies such as statins, fibrates and niacin are necessary even with cholesterol levels are low (Chavalitdhamrong, et al., 2007). Therefore, treatment for HP patients with MIC needs to focus short-term on inflammation and malnutrition through dietary counseling and medication. Once MIC is controlled, a more long-term therapy may need to look at controlling lipids associated with CVD risk.

Reverse epidemiology in cholesterol levels associated with HP introduces a number of questions concerning our understanding of CVD and findings from the Framingham study. The questions becomes whether nephrologists should recommend the same cut-points for HP as is normally used in general populations. Should nephrologists attempt to control malnutrition and inflammation first and focus on lipids once HP have MIC under control? Though statins can help control lipids they may also help control inflammation which in turn may help to regulate appetite and increase albumin levels suggestions that statin therapy may still need to be used in most HP. Finally, more clinical trials are needed to discover if reverse epidemiology is "normal" in HP or simply a new understanding of traditional risk factors.

438 HP Prospective

~ 3 years

sectional

sectional

Prospective ~ 4 years

**Design Study Findings** 

VLDL

number in

Reverse epidemiological effects for total cholesterol, LDL, LDL particle number, LDL, triglycerides, and

Reverse epidemiology in

hypoalbuminemia group; LDL, VLDL, and LDL particle number in inflamed group; total cholesterol, VLDL, large VLDL, triglycerides, Lp(a), LDL, and LDL particle number in hypoalbuminemia and inflamed group

Reverse epidemiology effect existed for LDL, large LDL, LDL particle size, and HDL

Patients with low cholesterol and high inflammation had an

**Author Year Sample Population Study** 

2010 105 HP Cross-

2009 117 HP Cross-

Type II Diabetes

2009 1255 HP with

**7. Conclusions** 

Bowden, et al

Bowden, et al

Bowden, et al

Krane, et al

In Press


Bergstrom, J. (1996). Anorexia in dialysis patients. *Seminars in Nephrology, 16*(3), 222-229.

Bolasco, P., Caria, S., Cupisti, A., Secci, R., & Saverio Dioguardi, F. (2011). A novel amino acids oral supplementation in hemodialysis patients: a pilot study. *Renal Failure, 33*(1), 1-5.

Malnutrition, Inflammation and Reverse Epidemiology in Hemodialysis Patients 309

Dungan, K. M., Guster, T., DeWalt, D. A., & Buse, J. B. (2007). A comparison of lipid and

Eisenhardt, S. U., Habersberger, J., Murphy, A., Chen, Y. C., Woollard, K. J., Bassler, N., et

Eisenhardt, S. U., Habersberger, J., & Peter, K. (2009). Monomeric C-reactive protein

Fleischmann, E. H., Bower, J. D., & Salahudeen, A. K. (2001). Risk factor paradox in hemodialysis: better nutrition as a partial explanation. *Asaio Journal, 47*(1), 74-81. Genest, J. (2010). C-reactive protein: risk factor, biomarker and/or therapeutic target? *The* 

Iseki, K., Kawazoe, N., & Fukiyama, K. (1993). Serum albumin is a strong predictor of death

Ji, S. R., Wu, Y., Potempa, L. A., Qiu, Q., & Zhao, J. (2006). Interactions of C-reactive protein

Kalantar-Zadeh, K. (2007). What is so bad about reverse epidemiology anyway? *Seminars in* 

Kalantar-Zadeh, K., Block, G., Humphreys, M. H., & Kopple, J. D. (2003). Reverse

Kalantar-Zadeh, K., Gutekunst, L., Mehrotra, R., Kovesdy, C. P., Bross, R., Shinaberger, C. S.,

Kalantar-Zadeh, K., & Kopple, J. D. (2001). Relative contributions of nutrition and

Kalantar-Zadeh, K., Kopple, J. D., Block, G., & Humphreys, M. H. (2001). A malnutrition-

hemodialysis patients. *American Journal of Kidney Diseases, 38*(6), 1251-1263. Kaysen, G. A. (2003). Serum albumin concentration in dialysis patients: why does it remain

Kaysen, G. A. (2009). Biochemistry and biomarkers of inflamed patients: why look, what to

Kilpatrick, R. D., McAllister, C. J., Kovesdy, C. P., Derose, S. F., Kopple, J. D., & Kalantar-

resistant to therapy? *Kidney international. Supplement*(87), S92-98.

with low-density lipoproteins: implications for an active role of modified C-reactive protein in atherosclerosis. *The International Journal of Biochemistry & Cell Biology,* 

epidemiology of cardiovascular risk factors in maintenance dialysis patients. *Kidney* 

et al. (2010). Understanding sources of dietary phosphorus in the treatment of patients with chronic kidney disease. *Clinical journal of the American Society of* 

inflammation to clinical outcome in dialysis patients. *American Journal of Kidney* 

inflammation score is correlated with morbidity and mortality in maintenance

assess. *Clinical Journal of the American Society of Nephrology : CJASN, 4 Suppl 1*, S56-

Zadeh, K. (2007). Association between serum lipids and survival in hemodialysis

*Canadian Journal of Cardiology, 26 Suppl A*, 41A-44A.

in chronic dialysis patients. *Kidney International, 44*, 115-119.

atherothrombotic risk. *Trends in Cardiovascular Medicine 19*(7), 232-237. Fasshauer, M., Klein, J., Lossner, U., & Paschke, R. (2003). Interleukin (IL)-6 mRNA

2 diabetes. *Current Medical Research and Opinion, 23*(11), 2689-2695.

*105*(2), 128-137.

*35*(3), 147-152.

*38*(4), 648-661.

*Dialysis, 20*(6), 593-601.

*International, 63*(3), 793-808.

*Diseases, 38*(6), 1343-1350.

63.

*Nephrology : CJASN, 5*(3), 519-530.

lipoprotein measurements in the fasting and nonfasting states in patients with type

al. (2009). Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques. *Circulation Research,* 

generation on activated platelets: the missing link between inflammation and

expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. *Hormone and Metabolic Research,* 


Bowden, R. G., Griggs, J., Wilson, R. L., & Gentile, M. (2009). Cholesterol values are poor

Bowden, R. G., Hebert, S., Wilson, R., Gentile, M., & Lanning, B. A. (2007). Comparison of

Bowden, R. G., & Wilson, R. L. (2010). Malnutrition, inflammation, and lipids in a cohort of

Cano, N. J., Miolane-Debouit, M., Leger, J., & Heng, A. E. (2009). Assessment of body

Carlson, T. H. (2004). Laboratory Data in Nutrition Assessment. In L. K. Mahan & S. Escott-

Ceciliani, F., Giordano, A., & Spagnolo, V. (2002). The systemic reaction during inflammation: the acute-phase proteins. *Protein and Peptide Letters, 9*(3), 211-223. Chand, D. H., Teo, B. W., Fatica, R. A., & Brier, M. (2008). Influence of vascular access type

Chavalitdhamrong, D., Danovitch, G. M., & Bunnapradist, S. (2007). Is there a reversal of

Chmielewski, M., Carrero, J. J., Nordfors, L., Lindholm, B., & Stenvinkel, P. (2008). Lipid

Corti, M. C., Guralnik, J. M., Salive, M. E., & Sorkin, J. D. (1994). Serum albumin level and

Costa, E., Rocha, S., Rocha-Pereira, P., Castro, E., Reis, F., Teixeira, F., et al. (2008). Cross-talk

Covinsky, K. E., Covinsky, M. H., Palmer, R. M., & Sehgal, A. R. (2002). Serum albumin

de Mutsert, R., Grootendorst, D. C., Indemans, F., Boeschoten, E. W., Krediet, R. T., &

Detsky, A. S., McLaughlin, J. R., Baker, J. P., Johnston, N., Whittaker, S., Mendelson, R. A., et

Diepeveen, S. H., Wetzels, J. F., Bilo, H. J., van Tits, L. J., & Stalenhoef, A. F. (2008).

hemodialysis patients. *The Journal of Vascular Access, 9*(4), 248-253.

dialysis patients. *Postgraduate Medicine, 122*(3), 196-202.

approach. *Journal of Nephrology, 21*(5), 635-644.

*American Medical Association, 272*(13), 1036-1042.

551.

548.

*50*(4), 631-637.

*Renal Nutrition 19*(2), 127-135.

*Parenteral and Enteral nutrition, 11*(1), 8-13.

*Netherlands journal of medicine, 66*(2), 53-61.

*Nephrol, 20*(2), 212-218.

Philadelphia, PA: Saunders.

*Practice 108*(2), c91-98.

markers of disease risk in a chronic disease population. *Clinical Lipidology, 4*(5), 545-

lipid measures and risk stratification among end-stage renal disease patients. *J* 

protein: energy status in chronic kidney disease. *Seminars in nephrology, 29*(1), 59-66.

Stump (Eds.), *Krause's Food, Nutrition, & Diet Therapy* (11th ed., pp. 436-454).

on outcome measures in patients on maintenance hemodialysis. *Nephron Clinical* 

reverse epidemiology in renal transplant recipients? *Seminars in Dialysis, 20*(6), 544-

disorders in chronic kidney disease: reverse epidemiology and therapeutic

physical disability as predictors of mortality in older persons. *The Journal of the* 

between inflammation,coagulation/fibrinolysis and vascular access in

concentration and clinical assessments of nutritional status in hospitalized older people: different sides of different coins? *Journal of the American Geriatrics Society,* 

Dekker, F. W. (2009). Association between serum albumin and mortality in dialysis patients is partly explained by inflammation, and not by malnutrition. *Journal of* 

al. (1987). What is subjective global assessment of nutritional status? *Journal of* 

Cholesterol in end-stage renal disease: the good, the bad or the ugly? [Review]. *The* 


Malnutrition, Inflammation and Reverse Epidemiology in Hemodialysis Patients 311

Sachdeva, M., Kovalchuk, O., Bitzer, M., & Mokrzycki, M. H. (2009). Vascular access type

Santos, N. S., Draibe, S. A., Kamimura, M. A., Canziani, M. E., Cendoroglo, M., Junior, A. G.,

patients without evidence of inflammation? *Artificial Organs, 27*(8), 681-686. Sattar, N., & Lowe, G. D. (2006). High sensitivity C-reactive protein and cardiovascular

Sprague, A. H., & Khalil, R. A. (2009). Inflammatory cytokines in vascular dysfunction and

Stenvinkel, P., Barany, P., Heimburger, O., Pecoits-Filho, R., & Lindholm, B. (2002).

Stolic, R. (2010). Obesity in renal failure--health or disease? *Medical Hypotheses, 75*(6), 497-

Sun, H., Koike, T., Ichikawa, T., Hatakeyama, K., Shiomi, M., Zhang, B., et al. (2005). C-

Taylor, L. M., Kalantar-Zadeh, K., Markewich, T., Colman, S., Benner, D., Sim, J. J., et al.

*Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation,* 

Trivedi, H., Xiang, Q., & Klein, J. P. (2009). Risk factors for non-fatal myocardial infarction

Tsirpanlis, G., Boufidou, F., Zoga, M., Triantafyllis, G., Fatourou, A., Stamatelou, K., et al.

Vaziri, N. D. (2009). Causes of dysregulation of lipid metabolism in chronic renal failure.

Wystrychowski, G., Kitzler, T. M., Thijssen, S., Usvyat, L., Kotanko, P., & Levin, N. W.

Xue, J. L., Dahl, D., Ebben, J. P., & Collins, A. J. (2003). The association of initial hemodialysis

Yeun, J. Y., Levine, R. A., Mantadilok, V., & Kaysen, G. A. (2000). C-Reactive protein

in hemodialysis patients. *Hemodialysis International, 13*(2), 197-204.

vascular disease. *Biochemical Pharmacology, 78*(6), 539-552.

interleukin-6? *Kidney International Supplement*(80), 103-108.

significance. *American Journal of Pathology, 167*(4), 1139-1148.

patients: a pilot study. *Journal of Renal Care, 37*(1), 16-24.

*The Journal of Vascular Access, 10*(3), 174-179.

*Biochemistry, 43*(Pt 4), 252-256.

500.

*Report*. (2002).

*24*(7), 2194-2200.

*Association, 24*(1), 258-266.

*Seminars in Dialysis, 22*(6), 644-651.

*Journal of Kidney Diseases, 42*(5), 1013-1019.

*Journal of Kidney Diseases, 35*(3), 469-476.

and changes in inflammatory markers in incident dialysis patients: a pilot study.

et al. (2003). Is serum albumin a marker of nutritional status in hemodialysis

disease: an association built on unstable foundations? *Annals of Clinical* 

Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of

reactive protein in atherosclerotic lesions: its origin and pathophysiological

(2011). Dietary egg whites for phosphorus control in maintenance haemodialysis

*and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final* 

and cardiac death in incident dialysis patients. *Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal* 

(2009). Low cholesterol along with inflammation predicts morbidity and mortality

(2009). Impact of switch of vascular access type on key clinical and laboratory parameters in chronic haemodialysis patients. *Nephrology Dialysis Transplantation,* 

access type with mortality outcomes in elderly Medicare ESRD patients. *American* 

predicts all-cause and cardiovascular mortality in hemodialysis patients. *American* 

patients and impact of race. *Journal of the American Society of Nephrology 18*(1), 293- 303.


Kopple, J. D. (1997). Nutritional status as a predictor of morbidity and mortality in

Kopple, J. D., Zhu, X., Lew, N. L., & Lowrie, E. G. (1999). Body weight-for-height

Krane, V., Winkler, K., Drechsler, C., Lilienthal, J., Marz, W., & Wanner, C. (2009).

Lippi, G., Favaloro, E. J., Montagnana, M., & Franchini, M. (2010). C-reactive protein and

Liu, Y., Coresh, J., Eustace, J. A., Longenecker, J. C., Jaar, B., Fink, N. E., et al. (2004).

Lowrie, E. G., & Lew, N. L. (1990). Death risk in hemodialysis patients: the predictive value

Moretti, H. D., Johnson, A. M., & Keeling-Hathaway, T. J. (2009). Effects of protein

Movilli, E., Brunori, G., Camerini, C., Vizzardi, V., Gaggia, P., Cassamali, S., et al. (2006). The

response in chronic hemodialysis patients. *Blood Purification, 24*(4), 387-393. Nanayakkara, P. W., & Gaillard, C. A. (2010). Vascular disease and chronic renal failure: new insights. [Review]. *The Netherlands Journal of Medicine, 68*(1), 5-14. Nishizawa, Y., Shoji, T., Ishimura, E., Inaba, M., & Morii, H. (2001). Paradox of risk factors

Phillips, A., Shaper, A. G., & Whincup, P. H. (1989). Association between serum albumin

treatment. *Nephrology Dialysis Transplantation, 17*(9), 1684-1688.

between facilities. *American Journal of Kidney Diseases, 15*(5), 458-482. Malgorzewicz, S., Aleksandrowicz-Wrona, E., Owczarzak, A., Debska-Slizien, A.,

humans. *Journal of Medicinal Food, 13*(6), 1490-1493.

maintenance dialysis patients. *Asaio Journal, 43*(3), 246-250.

303.

*56*(3), 1136-1148.

*291*(4), 451-459.

*Kidney Diseases, 54*(5), 902-911.

*Renal Nutrition, 19*(4), 298-303.

*334*(8677), 1434-1436.

*Laboratory Medicine 48*(12), 1693-1701.

patients and impact of race. *Journal of the American Society of Nephrology 18*(1), 293-

relationships predict mortality in maintenance hemodialysis patients. *Kidney Int,* 

Association of LDL cholesterol and inflammation with cardiovascular events and mortality in hemodialysis patients with type 2 diabetes mellitus. *American Journal of* 

venous thromboembolism: causal or casual association? *Clinical Chemistry and* 

Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. *The Journal of the American Medical Association,* 

of commonly measured variables and an evaluation of death rate differences

Rutkowski, B., & Lysiak-Szydlowska, W. (2010). Adipokines and nutritional status for patients on maintenance hemodialysis. *Journal of Renal Nutrition, 20*(5), 303-308. Montazerifar, F., Hashemi, M., Karajibani, M., & Dikshit, M. (2010). Hemodialysis alters

lipid profiles, total antioxidant capacity, and vitamins A, E, and C concentrations in

supplementation in chronic hemodialysis and peritoneal dialysis patients. *Journal of* 

kind of vascular access influences the baseline inflammatory status and epoetin

for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia? *American Journal of Kidney Diseases, 38*(4 Suppl 1), S4-7. Pecoits-Filho, R., Barany, P., Lindholm, B., Heimburger, O., & Stenvinkel, P. (2002).

Interleukin-6 is an independent predictor of mortality in patients starting dialysis

and mortality from cardiovascular disease, cancer, and other causes. *The Lancet,* 


**Part 3** 

**Complications**

Zimmermann, J., Herrlinger, S., Pruy, A., Metzger, T., & Wanner, C. (1999). Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. *Kidney International, 55*(2), 648-658.
