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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 5  |  Page : 785-789
Chronic Inflammation Increases Risk in Hemodialysis Patients

1 Department of Nephrology, Sina Hospital, Tehran, Iran
2 Department of Internal Medicine, Sina Hospital, Tehran, Iran
3 Department of Nephrology, Amir Alam Hospital, Medical Sciences/University of Tehran,Tehran, Iran
4 Department of Research and Development Center, Sina Hospital, Tehran, Iran

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Chronic inflammation is the cause of malnutrition and cardiovascular disease in hemodialysis patients. The purpose of this study was to assess C Reactive Protein (CRP) as an inflammatory marker and to define the relationship between CRP and other inflammatory and nutritional factors in this group of patients. One hundred and fourteen hemodialysis patients undergoing chronic dialysis (3 times a week for at least 4 hours) in two hemodialysis centers were enrolled in this cross-sectional study. Anthropometric and laboratory data including CRP, Il-6, hemoglobin, serum ferritin, triglyceride, cholesterol, albumin, total protein and transferrin were measured. The Kt/V for adequacy of dialysis was also calculated. There was a statistically signi­ficant correlation between the mean CRP and albumin, hemoglobin, and transferrin; while such relation was not found with BMI, ferritin, the length of dialysis, triceps skin fold thickness, mid arm circumference, mid arm muscle circumference, and Kt/V. We conclude that the negative relationship between CRP and albumin, transferrin, and hemoglobin suggests a correlation bet­ween inflammatory and nutritional factors.

Keywords: CRP, Albumin, IL-6, Hemodialysis

How to cite this article:
Razeghi E, Omati H, Maziar S, Khashayar P, Mahdavi-Mazdeh M. Chronic Inflammation Increases Risk in Hemodialysis Patients. Saudi J Kidney Dis Transpl 2008;19:785-9

How to cite this URL:
Razeghi E, Omati H, Maziar S, Khashayar P, Mahdavi-Mazdeh M. Chronic Inflammation Increases Risk in Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2023 Feb 2];19:785-9. Available from: https://www.sjkdt.org/text.asp?2008/19/5/785/42460

   Introduction Top

End-Stage Renal Disease (ESRD) is asso­ciated with an increase in mortality due to cardiovascular disease; the mortality rate after age, sex and diabetes adjustment is reported to be 9%, which is 10–20 times more than the general population. [1]

Although the common risk factors of arthro­sclerosis are widespread among ESRD patients, this cannot solely justify the high prevalence of cardiovascular diseases among these patients. Recent studies have proven that chronic in­flammation which is frequently noted in ESRD patients is the main cause of malnutrition, car­diovascular and atherosclerotic diseases. [2],[3]

CRP is the most important factor in the in­flammatory syndrome, and its production is controlled by several inflammatory mediators including IL–6 as the main cytokine in the acute phase of inflammation. CRP and IL–6 as well as serum albumin levels can predict mal­nutrition, arthrosclerosis, cardiac diseases, and death in ESRD patients. [4]

Serum albumin level was previously used as an index of patients' nutritional status; how­ever, recent studies have demonstrated that chronic inflammation increases serum albumin levels. Moreover, malnutrition may activate the inflammatory reactions by increasing the risk of infection.

Preliminary studies have reported a mea­ningful relation between CRP levels and serum albumin levels; though, the proposed corre­ lation is not stated in some recent studies. [3],[5],[6] The aim of the present study was to investigate CRP and its relation with other inflammatory and nutritional factors in hemodialysis patients.

   Patients and Methods Top

In this cross-sectional study, 114 hemodia­lysis patients undergoing chronic dialysis (3 times a week for at least 4 hours each time) in two hemodialysis centers were studied. Patients above 70 years of age with signs of infection as well as those representing acute vasculitis and inflammatory diseases were excluded. The required information was gathered through pre­designed questionnaires including the patients' medical history, clinical examinations and labo­ratory findings. The anthropometric information taken into account in this study was height, weight, body mass index (BMI), triceps skin fold thickness (TSF), mid arm circumference (MAC) and mid arm muscle circumference (MAMC).

The laboratory tests consisted of IL–6, hemo­globin, serum ferritin, triglyceride, cholesterol, albumin, total protein and transferrin. CRP was measured using Highly Sensitive ELISA and the amounts less than 10 mg/L were consi­dered normal. IL–6 and albumin were mea­sured using ELISA with BNDRMD system kit (Normal: 1.4–14.1 µg/ml) and colorimetry using Brom-Crozol kit (3.5–5.5 g/dL), respectively. Standard laboratory methods were used for other tests. The accuracy of dialysis (Kt/V) was calculated using the following formula: - In (R- 0.008*T) + (4–3.5*R) * 0.55 * UF/V.

   Statistical analysis Top

The data were entered in the SPSS software and were analyzed using T-test and chi-square.

   Results Top

The study patients included 70 males (61.4%) and 44 females (38.5%) with mean age of 48.6 ± 17 and 53 ± 16 years, respectively. CRP was 1110 mg/L in 67 patients (58.8%). The average CRP in patients with serum albumin levels less than 3.5 g/dL was significantly high, p= 0.018, [Table 1].

Similarly average CRP in patients with hemo­globin levels less than 9 g/dL and serum trans­ferrin less than 200 mg/dL was also signifi­cantly high (p= 0.007 and p< 0.001, respec­tively), [Table 1].

No significant correlation between CRP and BMI, ferritin, length of dialysis, TSF, MAC, MAMC, and KT/V was found.

The inter-group differences examined using chi-square were statistically meaningful (p value = 0.009).

   Discussion Top

CRP is an acute phase protein and its production in the liver is adjusted by various cytokines, particularly IL–6. It should be noted that in the absence of inflammation, the plasma level of CRP is low; however, it can increase by 1000 times in reaction to infla­mmatory phenomena. The apparent increase in CRP levels in hemodialysis patients indicates inflammation and is also known as a sensitive and independent marker for malnutrition. It is revealed that CRP is a powerful factor in predicting the complications and mortality in hemodialysis patients, especially in case of cardiovascular diseases. It therefore seems that a complicated interrelationship exists between malnutrition, inflammation, and arthrosclerosis. [7],[8]

Like other previous studies, in 41% of hemo­dialysis patients, CRP was higher than 10 mg/L and this indicates the higher incidence of inflammation in this group of patients. [9],[10] An inverse correlation was found between CRP levels and albumin, hemoglobin and transferrin in our study. Several studies have emphasized the relationship between the Nutritional status and clinical outcome, supporting the hypothesis that malnutrition can facilitate and predict mortality in ESRD patients. [2],[11]

Low levels of albumin considered as the indi­cator of malnutrition in hemodialysis patients can be influenced by infection and infla­mmation, as well. In addition, reductions in the albumin level, in cases where the CRP level is higher than 5.6 mg/L has been reported. More­over, studies have reported increased risk of cardiac diseases with high CRP levels without a decrease in albumin levels. Therefore, in the presence of normal albumin levels CRP levels may increase. [6],[12] In a study by Yeun et al, found CRP as a more sensitive and earlier marker for diagnosing inflammation in mainte­nance hemodialysis patients. [13] However, they could not specify the definite role of CRP in increasing the mortality rate in this group. [13] Iseki et al reported a similar significant rela­tion between albumin levels and CRP in 163 hemodialysis patients. [14] On the contrary, no significant correlation was reported between basic CRP and serum albumin level in hemo­dialysis patients. [15],[16]

No significant relation was documented bet­ween CRP, triglyceride and cholesterol, which are known as nutritional factors in hemo­dialysis patients. This can be attributed to either the fact that using statins in patients with hyperlipidemia can reduce the CRP level or the fact that the significant reduction of tri­glyceride and cholesterol serum may require longer period or a more severe inflammation. Reyes et al found a relationship between high CRP levels and low cholesterol serum in hemodialysis patients; the reverse relation indicates the inflammatory effect of uremia. [17]

IL–6 and cytokine secreted from monocytes are effective in the secretion of the acute phase proteins as well as adjusting immune respon­ses. Absence of a significant correlation bet­ween CRP levels and IL–6 in the present study was compatible with the study of Panichi et al[7] who concluded that renal failure could inde­pendently regulate the synthesis of IL–6 and CRP. In addition, they found that other factors in uremic patients could affect the synthesis of CRP as well as IL–6. In other words, higher levels of CRP in ESRD patients indicate its synthesis through unknown factors of the ure­mic syndrome. [7]

In our study, no meaningful relation was found between ferritin levels and CRP. Lower levels of ferritin (< 200 ng/ml) caused by iron deficiency, while iron overload as in hemocroma­tosis and thalassemia results in higher levels (> 2000 ng/ml). According to a study performed by Kalantarzadeh, there was no significant relationship between ferritin serum levels and CRP; however, this correlation became signifi­cant, following the elimination of the cases with ferritin lower than 200 ng/ml and higher than 2000 ng/ml. [18]

There was no significant correlation between CRP and TSF, MAC and MAMC suggesting that more intense and prolonged inflammation may influence this factors. [5]

There was no meaningful relationship bet­ween CRP, KT/V and length of dialysis. Con­sidering the existing studies, the possibility of inflammation in patients undergoing dialysis for a longer time is higher; [10] however, such a relationship was not found in our study.

We conclude that the acute phase response occurs in the majority of hemodialysis patients. A negative correlation between CRP and albumin, transferrin, and hemoglobin reveals the existence of relationship between CRP and other inflammatory and nutritional factors. We believe that measuring CRP as a marker of inflammation can be helpful in managing these patients. CRP was measured only once in our study and longitudinal and multiple measure­ments of CRP in future studies can be useful in achieving more comprehensive information.

   Acknowledgement Top

We would like to thank the Research and Development Center of Sina Hospital for pro­viding assistance in conducting this research.

   References Top

1.Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardio­vascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-5811  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Qureshi A, Alvestrand A, Divino-Filho J, et al. Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol 2002;13:S28-36.  Back to cited text no. 2    
3.Kaysen G, Dubin J, Muller H, et al. Relation­ ships among inflammation, nutrition and phy­siologic mechanisms establishing albumin level in hemodialysis patients. Kidney Int. 2002;61: 2240-9.  Back to cited text no. 3    
4.Honda H, Qureshi A, Heimburger O, et al. Serum Albumin, C-Reactive Protein, Interlukin­6, and Fetuin A as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 2006;47(1):139-4811  Back to cited text no. 4    
5.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. Kidney Int 2000;58(1):346-520  Back to cited text no. 5    
6.Menon V, Wang X, Greene T, et al. Relation­ship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney diseaseDAm J Kidney Dis 2003;42(1): 44-5211  Back to cited text no. 6    
7.Panichi V, Migliori M, De Pietro S et al. C­reactive protein in patients with chronic renal diseases. Ren Fail 2001;23(3-4):551-620  Back to cited text no. 7    
8.Kalantar-Zadeh K, Kopple J. Relative contri­bution of nutrition and inflammation to clinical outcome in dialysis patients. Am J Kidney Dis 2001;38(6):1343-50.  Back to cited text no. 8    
9.Lacson EJ Jr, Levin N. C-reactive protein and end-stage renal disease. Semin Dial 2004;17 (6):438-480  Back to cited text no. 9    
10.Stenvinkel P. Inflammation in end-stage renal failure: Could it be treated? Nephrol Dial Transplant 2002;17(8):33-811  Back to cited text no. 10    
11.Hung C, Chen Y, Chou C, Yang C. Nutritional and Inflammatory markers in the prediction of mortality in Chinese hemodialysis patients. Nephron Clin Pract 2005;100(1):c20-6.  Back to cited text no. 11    
12.Kaysen G, Greene T, Daugirdas J, et al. Longitudinal and cross sectional effects of C­reactive protein, equilibrated normalized protein catabolic rate, and serum bicarbonate on crea­tinine and albumin levels in dialysis patients. Am J Kidney Dis 2003;42(6):1200-1111  Back to cited text no. 12    
13.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(3):469-76.  Back to cited text no. 13    
14.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(8):1956-600  Back to cited text no. 14    
15.Nascimento MM, Pecoits-Filho R, Qureshi AR, et al. The prognostic impact of fluctuating levels of C-reactive proteins in Brazilian haemo­dialysis patients: a prospective study. Nephrol Dial Transplant 2004;19(11):2803-9.  Back to cited text no. 15    
16.Tzoulaki I, Murray GD, Lee AJ, Rumley A, Lowe GD, Fowkes FG. C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral athero­sclerosis in the general population Edinburgh artery study. Circulation 2005;112(7):976-83.  Back to cited text no. 16    
17.Fernandez-Reyes MJ, Alvarez-Ude F, Sanchez R, et al. Inflammation and malnutrition as pre­dictors of mortality in patients on hemodialysis. J Nephrol 2002;15(2):136-43.  Back to cited text no. 17    
18.Kalantar-Zadeh K, Rodriguez RA, Humphreys MH. Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant 2004;19(1):141-9.  Back to cited text no. 18    

Correspondence Address:
Effat Razeghi
Assistant Professor of Nephrology, Sina Hospital, P.O. Box 11367-46911, Tehran
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Source of Support: None, Conflict of Interest: None

PMID: 18711296

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