**7. References**


All hemodialysis patients, diabetic or nondiabetic, are at markedly increased CV risk, with chronic renal disease alone currently considered a coronary heart disease risk equivalent. A large number of risk factors for CV disease and decreased survival that are related or unrelated to the dialysis procedure have been identified. Since no data are available about the outcome comparing hemodialysis patients with comorbidities with those without, it is not possible to suggest increased benefits for survival for hemodialysis patients without comorbidities. Cardiovascular risk factor modification should be undertaken for all dialysis patients with or without comorbidities, given that they are considered a coronary heart

Afsar, B., Elsurer, R., Akgul, A., Sezer, S., & Ozdemir, FN. (2009). Factors related to silent

Andress, DL. (2008). Bone and mineral guidelines for patients with kidney disease: a call for

Arici, M., Walls, J. (2001). End stage renal disease, atherosclerosis, and cardiovascular

Asakimori, Y., Yorioka, N., Tanaka, J., Takasugi, N., Harada, S., Shigemoto, K., Yamashita,

Bodor, GS., Survant, L., Voss, EM., Smith, S., Porterfield, D., & Apple, FS. (1997). Cardiac

Borawski, J., Mysliwic, M. The hematocrit corrected erythrocyte sedimentation rate can be

Cheung, AK.,Sarnak, MJ., Yan, G., Dwyer, JT., Heyka, RJ., Rocco, MV., Teehan, BP. et

Drüeke, TB., Massy, ZA. (2009). Beta 2 microglobulin. *Seminars in Dialysis.* Vol.22, No: 4, pp.

Ekart, R., Hojs, R., Hojs-Fabjan, T., & Balon, BP.(2005). Predictive value of carotid intima

Ekart, R., Hojs, R., Bevc, S., & Balon, BP. (2008). Asymptomatic atherosclerosis and

patients. *Kidney International*. Vol.58, No:1, pp.353-362, ISSN0085-2538 Cianciolo, G., Cli, L., La Mana, G., Donati, G., D'Addio, F. Comai, G., Ricci, D., et al. (2007).

*Artificial Organs*. Vol 30, No: 10, pp. 864-878, ISSN0391-3988

*of Kidney Disease*. Vol.44, No:1, pp.112-120,0272-6386.

*Chemistry*. Vol. 43, No:3, pp.476-484, ISSN0009-9147

myocardial damage in hemodialysis patients. *Renal Failure*. Vol.31, No:10, pp.933-

revision. *Clinical Journal of the American Society of Nephrology*. Vol.3, No:1, pp.179-

mortality: Is C- reactive protein the missing link? *Kidney International*. Vol.59, No:2,

K. et al. (2004). Association between ENOS gene polymorphism and cardiovascular events in nondiabetic hemodialysis patients: a prospective study. *American Journal* 

troponin T composition in normal and regenerating human skeletal muscle. *Clinical* 

useful in diagnosing inflammation in hemodialysis patients. (2001). *Nephron*.

al.(2000). Atherosclerotic cardiovascular disease risks in chronic hemodialysis

Is beta 2 microglobulin- related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach. *The Internal Journal of* 

media thickness in hemodialysis patients. *Artificial Organs*. Vol. 29, No: 8, pp. 615-

hypertension in nondiabetic patients with chronic kidney disease. *Artificial Organs*.

**6. Conclusion** 

disease equivalent.

**7. References** 

941, ISSN 0886-022X

183, ISSN1555-9041

378-380, 0894-0959

619, ISSN0160-564X

pp. 407-414, ISSN0085-2538

Vol.89, No:4, pp.381-383, 0028-2766

Vol. 32, No: 3, pp.220-225, ISSN0160-564X


Determinants of Cardiovascular Risk in Hemodialysis Patients Without Significant Comorbidities 295

Merkus, MP., Jager, KJ., Dekker, FW., de Haan, RJ., Boeschoten, EW., & Kredit, RT. (2000).

*American Journal Of Kidney Disease*. Vol.35, No:1, pp. 69-79, ISSN 0272-6386 Miskulin, D., Bragg-Gresham, J., Gillespie, BW., Tentori, F., Pisoni, RL., Tiqhiouart, H.,

O' Sullivan, AJ., Kelly, JJ. (2007). Insulin resistance and protein catabolism in non diabetic hemodialysis patients. *Kidney International*. Vol.71, No:2, pp.98-100, ISSN0085-2538 Okuno, S., Ishimura, E., Kohno, K., Fujino-Katoh, Y., Maeno, Y., Yamakawa, T., Inaba, M., &

Parfrey, PS. (2000). Cardiac disease in dialysis patients: diagnosis, burden of disease,

Peng, Y., Liu, H., Liu, F., Ouyang, L., Cheng M, Gao L, Pan F. et al. (2008). Atherosclerosis is

Sakkas, GK., Karatzaferi, C., Zintzaras, E., Giannaki, CD., Liakopoulos, V., Lavdas, E.,

*and Comparative Physiology*. Vol. 295, No: 6, pp.1721-1729, ISSN0363-6119 Sarnak, MJ., Levey, AS., Scoolwerth, AC., Coresh, J., Culleton B, Hamm, LL., McCullough,

Schlieper, G., Brandenburg, V., Djuric, Z., Damjanovic, T., Markovic, N., Schurgers, L.,

Stenvinkel, P. (2002). İnflammation in end-stage renal failure: could it be treated? *Nephrology* 

Stenvinkel, P., Alvestrand, A. (2002). Inflammation in end-stage renal disease: sources,

Stenvinkel, P. (2006). İnflammation in end-stage renal disease: the hidden enemy. *Nephrology*

Tomson, CRV. (2000). Cardiovascular disease in chronic renal failure. In: *Comprehensive* 

*Dialysis Transplantation*. Vol.17, suppl.8, pp. 33-38, ISSN0931-0509

( Carlton). Vol. 11, No:1, pp.36-41, ISSN 1320-5358

Elsevier, ISBN 07234 32589, Philadelphia

patients. *Nephrology (Carlton).* Vol.13, No: 7, pp. 579-586, ISSN1320-5358 Pepys, MB., Baltz, ML.(1983). Acute phase proteins with special reference to C-reactive

Vol. 4, no:11, pp.1818-1826, 1555-9041

Vol.15, Suppl.5, pp. L58-68, ISSN0931-0509

*Immunology*. Vol: 34, pp. 141-212, ISSN 0065-2776

ISSN0931-0509

0009-7322

0894-0959

pp161-168, ISSN1420-4096

Predictors of poor outcome in chronic dialysis patients: The Netherlands Cooperative Study on the Adequacy of Dialysis. The NECOSAD Study Group.

Levey, AS. et al. (2009). Key comorbid conditions that are predictive of survival among hemodialysis patients. *Clinical Journal of the American Society of Nephrology.*

Nishizawa, Y. (2009). *Nephrology Dialysis Transplantation.* Vol.24, No: 2, pp.571-577,

prognosis, risk factors and management. *Nephrology Dialysis and Transplantation,*

associated with plasminogen activator inhibitor type-1 in chronic hemodialysis

protein and related proteins (pentaxins) and serum amyloid a protein. *Advances in* 

Damani, E. et al. (2008). Liver fat, visceral adiposity, and sleep disturbances contribute to the development of insulin resistance and glucose intolerance in nondiabetic dialysis patients. *American Journal of Physiology: Regulatory, Integrative* 

PA. et al. (2003). Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. *Circulation*. Vol. 108, No:17, pp. 2154-2169, ISSN

Kruger, T. et al. (2009). Risk factors for cardiovascular calcifications in-diabetic Caucasian Hemodialysis patients. *Kidney Blood Pressure Research.*. Vol.32, No: 3,

consequences, and therapy. *Seminars in Dialysis*. Vol.15, No:5, pp. 329-337, ISSN

*Clinical Nephrology (2nd edition).* Johnson RJ & Feehally J, pp. 887-904, Mosby-


Kawai, K., Kawashima, S., Miyazaki, T., Tajiri, E., Mori, M., Kitazaki, K., Shirotani, T. et al.

Kaysen, GA., Eiserich, JP. ( 2004 ). The role of oxidative stres-altered lipoprotein structure

Kumar, J., Shah, SV. ( 2005). Kidney disease as an independent risk factor for cardiovascular events. *Journal of Renal Nutrition.* Vol. 15, No:1, pp. 99-104. ISSN 1051-2276 Kunstmann, S., Vukusich, A., Michea, L., Varela, C., Allende, I., Bravo S, Gainza D, et al.

Kuragano, T., Kida, A., Furuta, M., Nanami, M., Otaki, Y., Hasuike, Y., Nonoguchi, H., &

Lagrand, WK., Niessen, HWM., Wolbink, GJ., Jaspars, LH., Visser, CA., Verheugt, FW.,

Levin, A., Li, YC. (2005). Vitamin D and its analogues: do they protect against

Lin-Tan, DT., Lin, JL., Wang, LH., Wang, LM., Huang, LM., Liu, L., Huang, JY., & Huang,

London, GM; Drüeke, TB. (1997). Atherosclerosis and arteriosclerosis in chronic renal failure. *Kidney International*. Vol.51, No. 6, pp. 1678-1695, ISSN0085-2538 London, GM., Marchais, SJ., Metivier, F., & Guerin, AP. (2000). Cardiovascular risk in end

Ma, KW., Grene, EL., Raij, L. Cardiovascular risk factors in chronic renal failure and

Mailloux, LU., Bellluci, AG., Wilkes, BM.,Napolitano, B., Mosset, RT., Lesser, M., &

Mailloux, LU., Henrich, WL. (2010). Patient survival and maintenence dialysis.

McLaurin, MD., Apple, FS., Voss, EM., Herzog, CA., & Sharkey, SW. (1997). Cardiac

skeletal muscle. *Clinical Chemistry*. Vol.43, No:6, pp.976-982, ISSN 0009-9147

wwwUpToDatecom, Editors; Berns JS& Post WT, pp.1-27

*Medica de Chile*. Vol. 137, No:3, pp: 351-360, ISSN0034-9887

*Artificial Internal Organs*. Vol. 56, No:4, pp. 326-332, ISSN1058-2916

*Society of Nephrology.* Vol. 18, No: 8, pp. 2385-2391, ISSN1046-6673

pp.99-107, ISSN0914-5087

548,ISSN 1046-6673

ISSN0009-7322

No: 5, pp.1973-1981, ISSN0085-2538

Suppl 5, pp.97-101, ISSN0931-0509

No:3, pp.164-169, ISSN 1058-2916

pp.505-513, 0272-6386

(2010). Serum Beta 2 microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients. *Journal of Cardiology*. Vol.55, No:1,

and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. *Journal of American Society of Nephrology.* Vol:15, No:3, pp. 538-

(2009). Cardiovascular assessment of non diabetic patients on hemodialysis. *Revista* 

Nakanishi, T. (2010). The impact of beta 2microglobulin clearence on the risk factors of cardiovascular disease in hemodialysis patients. *American Society for* 

Meijer, CJ,. et al. (1997). C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction*. Circulation*. Vol.95, No:1, pp. 97-103,

cardiovascular disease in patients with kidney disease? *Kidney International*. Vol.68,

YL. (2007). Fasting glucose levels in predicting 1-year mortality in patients who do not have diabetes and are on maintenance hemodialysis. *Journal of the American* 

stage renal disease: vascular aspects. *Nephrology Dialysis Transplantation*. Vol.15,

hemodialysis populations. (1992). *American Journal of Kidney Disease*. Vol. 19, No:6,

Bluestone, PA. (1991). Mortality in dialysis patients: analyses of the causes of death. *American Journal of Kidney Diseases*. Vol.18, No:3, pp. 326-335, ISSN0272-6386 Mailloux, LU., Napolitano, B., Bellucci, AG., Mossey, RT., Vernace, MA., & Wilkes, BM.

(1996). The impact of co-morbid risk factors at the start of dialysis upon the survival of ESRD patients. *American Society for Artificial Internal Organs*. Vol 42,

troponin I, cardiac troponin T, and creatinine kinase MB in dialysis patients without ischemic heart disease: Evidence of cardiac troponin T expression in


**16** 

*USA* 

*Baylor University , Waco, TX* 

**Malnutrition, Inflammation and Reverse Epidemiology in Hemodialysis Patients** 

Rodney G. Bowden, Neil A. Schwarz and Brian D. Shelmadine

Reverse epidemiology, or risk factor paradox, has been used to describe the observed effect that traditional risk factors for cardiovascular disease may not necessarily signify the same risk for hemodialysis patients (HP) as for healthy populations. In fact, recent published findings have suggested counter-intuitive outcomes (Chavalitdhamrong, Danovitch, & Bunnapradist, 2007; Tsirpanlis et al., 2009) regarding the role cholesterol may play in disease progression in HP with chronic inflammation and malnutrition comorbidities (Dungan, Guster, DeWalt, & Buse, 2007). However, contemporary experimental studies regarding reverse epidemiology are lacking. The few published findings on this topic suggest chronic inflammation, as measured by C-reactive protein (CRP), and malnutrition, as measured by albumin, is associated with normal cholesterol levels yet higher levels of mortality (Chavalitdhamrong, et al., 2007; Chmielewski, Carrero, Nordfors, Lindholm, & Stenvinkel,

In contrast, traditional risk factors such dyslipidemia, hyperhomocysteinemia, obesity, or hypertension may provide protective effects in HP, at least in the short term (Kalantar-Zadeh, Block, Humphreys, & Kopple, 2003). Important predictors of clinical outcomes in HP are protein-energy wasting (malnutrition) (PEM) and inflammation (Fleischmann, Bower, & Salahudeen, 2001; Kalantar-Zadeh & Kopple, 2001; Kopple, 1997; Kopple, Zhu, Lew, & Lowrie, 1999; Lowrie & Lew, 1990; Nishizawa, Shoji, Ishimura, Inaba, & Morii, 2001). Because inflammation and PEM are interconnected and similarly affect markers of nutritional status both are considered part of a malnutrition inflammation complex (MIC) (Kalantar-Zadeh, et al., 2003; Kalantar-Zadeh & Kopple, 2001; Kalantar-Zadeh, Kopple, Block, & Humphreys, 2001). Thus, this chapter will address inflammation, malnutrition, cholesterol, and the overall concept of reverse epidemiology in HP relative to MIC as well as

Initially, the inflammatory response is a defense mechanism to cellular injury or pathogenic invasion. The acute response includes vasodilatation, hyperemia and vascular permeability and can be detected within a relatively short amount of time (minutes to days) via an increase in neutrophils and the presence of fluid protein exudates (Sprague & Khalil, 2009).

the implications of this information on short- and long-term treatment.

**2. Inflammation in hemodialysis patients** 

**2.1 Acute vs. chronic inflammation** 

**1. Introduction** 

2008).

