Year : 2009 | Volume
: 20 | Issue : 5 | Page : 811--815
C-Reactive protein, a valuable predictive marker in chronic kidney disease
Georgi Abraham, Varun Sundaram, Vivek Sundaram, Milly Mathew, Nancy Leslie, Vijiaboobbathi Sathiah
Department of Internal Medicine, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, Tamil Nadu, India
Department of Internal Medicine, SRMC, Porur, Chennai, Tamil Nadu
The aim of this study was to look for correlation between the markers for malnutrition and inflammation, and atherosclerosis in pre-dialysis chronic kidney disease (CKD) patients. This observational study involved 100 pre dialysis patients (age 57 ± 12 years) from the out-patient and in-patient departments over a span of two years. Informed consent was obtained from all the study patients. Highly sensitive C-reactive protein (hsCRP) was assayed as a marker of chronic inflammation. Nutritional status was assessed using serum albumin and body mass index (BMI). Clinical and laboratory data were collected and a carotid doppler study was performed using duplex ultrasonography method to look for carotid artery stenosis. Renal function was assessed by calculating the estimated glomerular filtration rate (GFR) by the MDRD-2 formula. These data were later analyzed using descriptive statistics, Chi-square test and the students«SQ» t test. The mean GFR was 28.3 ± 16.4 mL/min/1.73m 2 . The mean value of CRP was 14.3 ± 11.4 mg /L. Sixty-seven percent of patients had elevated CRP (> 6 mg/L) levels. Patients with higher CRP levels showed lower mean serum albumin levels (3.2 ± 0.7 gm/dL) (P < 0.01). Only three patients had evidence of hemodynamically significant carotid disease (lumen diameter < 50%) with no statistical significance. Low serum albumin levels were associated with low hemoglobin levels (< 10 gm/dL), low GFR and presence of diabetes mellitus. Our results indicate that a high degree of inflammation and malnutrition exists in pre-dialysis patients as seen by high CRP values and low serum albumin levels. Synergism of these factors could contribute to atherosclerosis in CKD apart from the classic risk factors. To our knowledge, this is the first study, which has compared these markers of inflammation in pre-dialysis patients in developing countries.
|How to cite this article:|
Abraham G, Sundaram V, Sundaram V, Mathew M, Leslie N, Sathiah V. C-Reactive protein, a valuable predictive marker in chronic kidney disease.Saudi J Kidney Dis Transpl 2009;20:811-815
|How to cite this URL:|
Abraham G, Sundaram V, Sundaram V, Mathew M, Leslie N, Sathiah V. C-Reactive protein, a valuable predictive marker in chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 Aug 14 ];20:811-815
Available from: http://www.sjkdt.org/text.asp?2009/20/5/811/55367
The prevalence of chronic kidney disease (CKD) varies widely in Indian population and is found to be 785 per million population.  Increasing evidence, accrued in the past decades, indicates that the adverse outcomes of CKD, such as kidney failure, cardiovascular disease (CVD) and premature death can be prevented or delayed. CVD has been found to be responsible for the majority of mortality and morbidity in this patient population and accounts for 40 to 50% of all deaths in end-stage renal disease (ESRD) patients. Also, mortality rates due to CVD are approximately 15-times higher in the ESRD population than in the general population. The Second National Healthy and Nutrition Examination Survey (NHANES II) showed that an estimated glomerular filtration rate (GFR) of less than 70 mL/min/1.73m 2 was associated with a 68% increase in the risk of death from any cause and a 51% increase in the risk of death from CVD.  In the Atherosclerosis Risk in Communities Study, an estimated GFR of 1559 mL/min/1.73m 2 at baseline was associated with a 38% increase in the risk of CVD.  The higher prevalence of atherosclerotic lesions in uremic patients has been amply documented by autopsy studies.  These observations have validated the hypothesis of accelerated atherosclerosis in renal failure. Recent studies have accumulated compelling evidence for a role of Creactive protein (CRP) in improving risk prediction in this setting.  In the large Cardiovascular Health Study, renal insufficiency was independently associated with elevation of CRP, which may indicate an important pathway mediating the increased cardiovascular risk in persons with kidney disease.  Elevated CRP levels are associated with an increase in the carotid intima-media area in CKD-pre-dialysis and dialysis patients.  In patients evaluated for chest pain, there was a significant correlation between severe coronary artery disease (CAD) and degree of carotid stenosis. 
Low serum albumin concentrations are highly associated with increased mortality risk in patients on renal replacement therapy.  However, serum albumin is to a large extent influenced by factors other than malnutrition, and high concentration of acute phase reactants such as CRP are correlated with low serum albumin in malnourished hemodialysis patients.  In malnutrition, increased oxidative stress in combination with chronic inflammation might lead to an increased risk of atherosclerosis. Therefore, the terminology malnutrition inflammation complex syndrome (MICS) or malnutrition inflammation and atherosclerosis (MIA) syndrome has been prepared to indicate the combination of these two conditions in these patients , Chronic inflammation may be the missing link that actually ties protein energy malnutrition to morbidity and mortality in these individuals.
Materials and Methods
This was an observational study conducted in a tertiary care center in South India and enrolled both out-patients and in-patients belonging to different socio-economic strata. The inclusion criteria included the following:
age greater than 18 years,CKD patients who were not initiated on dialysis,HsCRP value > 6 mg/L was taken as the cut off point for deciding the inflammatory status.
Patients with active infection, malignancy, on renal replacement therapy and renal transplant recipients were excluded from the study. Highly sensitive C-reactive protein (hs-CRP) was analyzed using Nephelometry method (DADE BEHRING) utilizing latex particles coated with CRP monoclonal antibodies. Serum albumin was measured by bromocresol blue method. The right and left carotid arteries were examined with a duplex scanner by the same trained radiologist. Internal carotid artery narrowing of hemodynamic significance ( 2 with a mean GFR of 28.3 ± 16.4 mL/min/1.73m 2 . The mean BMI was 23.64 ± 4.7 kg/m 2 .
The mean value of HsCRP was 14.3 ± 11.4 mg/L (range 0.36 - 44.2 mg/L). Sixty-seven patients showed a HsCRP level > 6 mg/L. There was no significant relationship between CRP levels and age, gender, diabetes mellitus, hypertension, nutritional data like BMI and hemoglobin levels. Patients with higher HsCRP levels showed lower serum albumin levels compared with patients with lower HsCRP levels (3.2 ± 0.7 vs 3.6 ± 0.5 g/dL, P  Although the results of this study do not rule out the influence of procedural variables on the inflammatory state, the number of patients with high HsCRP levels in our non-dialysis population was similar to the prevalence reported by Owen and Lowrie in a dialysis population.  This points to the fact that CKD patients, even in predialysis stage, show signs of inflammation.
The average values of HsCRP were higher in this study (14.37 ± 11.4 mg/L) compared to earlier studies by Ortega et al (8.3 ± 14.2 mg/L) and Menon et al (2.2 mg/L) in pre-dialysis pa tients. , There was no correlation of HsCRP level with diabetic status and hypertension as seen in previous reports. , Stenvinkel et al reported that there was no association of HsCRP levels with gender and diabetic status in CKD patients.  He showed that the prevalence of malnutrition assessed by subjective global assessment (SGA) was significantly higher in patients with elevated HsCRP, but we did not observe any correlation between CRP and BMI in the present study. Menon et al had shown that HsCRP levels increased with age but such correlation was not seen in this study.  Ortega et al had observed that the mean value of hemoglobin was lower (P 6 mg/L) was lower than in patients with low CRP values (3.2 ± 0.7 vs 3.6 ± 0.5 g/dL, P  (3.5 ± 0.4 vs 3.8 ± 4 g/dL, P  These data support the hypothesis that protein energy malnutrition and anorexia of uremia may be part of a malnutrition inflammation complex mediated by cytokines and this process begins in subjects with reduced GFR. However, serum albumin level may reflect the nutritional status and as a negative acute phase reactant. It is thus difficult to ascertain whether the relationship between CRP and albumin is caused by an association between inflammation and malnutrition or an association between one marker of inflammation and another.
Significant carotid disease (> 50 percent stenosis) was present only in three patients. Hence, its association with CRP and serum albumin could not be studied. We would need a larger sample population to ascertain this relationship. The drawbacks of this study are the relatively small sample size compared to earlier studies. Smoking, a risk factor for atherosclerosis was not studied as women formed a significant number of patients and were non-smokers. Though carotid-intima media thickness is the earliest marker for atherosclerosis, we have assessed carotid stenosis as in the Framingham study. However, the smaller sample size with the majority being non-smokers in the study group, could also explain the inability to study the association between inflammation, malnutrition and carotid atherosclerosis.
To our knowledge, this is the first study, which has compared these markers in non-dialysis CKD patients from a developing country. This study shows a high rate of inflammation in non dialysis patients as seen by high CRP levels. As in dialysis patients, high CRP levels in non dialysis patients are associated with lower serum albumin levels. It is possible that inflammatory processes precipitated by uremia per se could play a role in the development of malnutrition and atherosclerosis in patients with kidney disease.
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