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| Year : 2009 | Volume
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| Issue : 5 | Page : 811-815 |
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| C-Reactive protein, a valuable predictive marker in chronic kidney disease |
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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
Click here for correspondence address and email
| Date of Web Publication | 2-Sep-2009 |
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 Abstract | | |
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' 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;20:811-5 |
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 Oct 30];20:811-5. Available from: https://www.sjkdt.org/text.asp?2009/20/5/811/55367 |
| Introduction | |  |
The prevalence of chronic kidney disease (CKD) varies widely in Indian population and is found to be 785 per million population. [1] 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. [2] 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. [3] The higher prevalence of atherosclerotic lesions in uremic patients has been amply documented by autopsy studies. [4] 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. [5] 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. [6] Elevated CRP levels are associated with an increase in the carotid intima-media area in CKD-pre-dialysis and dialysis patients. [7] In patients evaluated for chest pain, there was a significant correlation between severe coronary artery disease (CAD) and degree of carotid stenosis. [8]
Low serum albumin concentrations are highly associated with increased mortality risk in patients on renal replacement therapy. [9] 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. [10] 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 [11],[12] 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 (<_ 50%) was defined as an internal carotid spectrum with a peak velocity below 1.25 m/sec and minimal spectral broadening during the deceleration phase of systole. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula using the GFR calculator. Descriptive statistics such as mean and standard deviation were used for continuous variables.
Chi-square test has been applied to find any association between two categorical variables. Student's t-test has been used to find any significant difference between the normal and abnormal groups of variables with respect to average values.
| Results | | |
There were 100 patients with mean age of 57 ± 12 years. Fifty-five percent were men and the prevalence of diabetes mellitus was 59%. Minimum and maximum GFR were 4.17 and 73.21 mL/min/1.73m 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 < 0.01). There was also an inverse correlation between HsCRP levels and the GFR (P value < 0.05).
Lower serum albumin levels correlated with presence of diabetic mellitus, low hemoglobin levels (< 10 g/dL) and a low GFR. There was no correlation between serum albumin levels and hypertension or BMI.
Carotid Doppler was studied in 81 patients. Only three patients in this study had evidence of hemodynamically significant carotid disease defined as lumen diameter < 50%.
| Discussion | | |
The high HsCRP levels in Indian CKD patients indicate the high prevalence of inflammation in non-dialysis patients. However, this was a cross sectional study and serial HsCRP levels were not monitored to assess the persistence of inflammation. Being a developing country, the great majority of patients cannot afford renal replacement therapy due to non-availability of governmental or health insurance support systems. The percentage of CKD patients in stage5 getting renal replacement therapy is very low in India. Diabetic nephropathy was the cause of CKD in 59% indicating its high prevalence in India. As in the dialysis population, high HsCRP levels in pre-dialysis patients predicts lower serum albumin concentration. [13] 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. [14] 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. [15],[16] There was no correlation of HsCRP level with diabetic status and hypertension as seen in previous reports. [15],[16] Stenvinkel et al reported that there was no association of HsCRP levels with gender and diabetic status in CKD patients. [7] 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. [16] Ortega et al had observed that the mean value of hemoglobin was lower (P < 0.05) in patients with high HsCRP levels. However, it is surprising that there was no correlation between hemoglobin levels and HsCRP levels in the present study. There was a significant relationship between declining renal function and HsCRP levels (P < 0.05). However, this association was largely due to the high HsCRP levels in patients with Stage-5 CKD. This could probably be explained by the lower mean age of 52 ± 5 yrs in this group compared to the total mean age of 57 ± 12 yrs. There was also a low percentage (44%) of diabetics in Stage-5 CKD. Ortega et al and Menon et al found no correlation of CRP levels and GFR in their studies. In contrast to our findings, Panichi et al noted higher HsCRP le-vels in patients with a creatinine clearance less than 20 mL/min (mean CRP 7.4 ± 6.3 mg/L) compared with those with a creatinine clearance greater than 20 mL/min (mean CRP 2.76 ± 4.35 mg/L). CRP levels in our non-dialysis patients correlated inversely with serum albumin (P value < 0.01) as in the dialysis population. Stenvinkel et al had established that patients with pre-ESRD CKD who were found to be malnourished, had markers consistent with the presence of inflammation. In this study, patients with high CRP levels showed lower serum albumin levels but without the presence of other markers of malnutrition like lower BMI. The mean serum albumin level in patients with high CRP (> 6 mg/L) was lower than in patients with low CRP values (3.2 ± 0.7 vs 3.6 ± 0.5 g/dL, P < 0.01). These results were similar to those observed by Ortega et al [15] (3.5 ± 0.4 vs 3.8 ± 4 g/dL, P < 0.05). Menon et al has shown that a high CRP level was associated with 0.07 g/dL lower mean albumin levels compared with patients having low CRP values. [15] 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.
| Conclusion | | |
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.
| References | | |
| 1. | Abraham G, Moorthy AV, Aggarwal V. Chronic Kidney Disease: a silent epidemic in Indian subcontinent-strategies for management. J Ind Med Assoc 2006;104(12):689-91.  |
| 2. | Muntner P, He J, Hamm L, Loria C, Whetton PK. Renal insufficiency and subsequent death from cardiovascular disease. J Am Soc Nephrol 2002;13:745-53. |
| 3. | Manjunath G, Tighromart H, Ibrahim H. Level of kidney function as a risk factor for cardiovascular outcomes in the elders. Kidney Int 2003;63:1121-9. |
| 4. | Clyne N, Lins LE, Petrsson SK. Occurrence and significance of heart disease in Uraemia. Scan J Urol Nephrol 1986;20:307-11. |
| 5. | Arici M, Walls J. ESRD, atherosclerosis and cardiovascular mortality: is C-reactive protein the missing link? Kidney Int 2001;59:407-14. [PUBMED] [FULLTEXT] |
| 6. | Shilpak MG. Elevation of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 2003;107:32-7. |
| 7. | Stenvinkel P, Heimburger O, Paultre F, et al. Association between malnutrition, inflammation and atherosclerosis is chronic renal failure. Kidney Int 1999;55:1899-911. |
| 8. | Kallikazaros I, Tsioufes C, Sides S, Stefandes C, Toutouzas P. Carotid artery disease as a marker for the presence of severe coronary artery disease in patients evaluated for chest pain. Stroke 1999;30:1002-7. |
| 9. | Lowrie EG. Death risk in haemodialysis patients. Am J Kidney Dis 1994;24:1010-8. |
| 10. | Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardio vascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-58. [PUBMED] [FULLTEXT] |
| 11. | Kalantar-Zadeh K, Kopple JD. Relative contributions of nutritional and inflammation to clinical outcome in dialysis patients. Am J Kidney Dis 2001;38:1343-50. [PUBMED] [FULLTEXT] |
| 12. | Pecoits-Filho R. Malnutrition Inflammation: Atherosclerosis (MIA) syndrome Heart of the matter. Nephrol Dial Transplant 2002;17(Suppl 11):528. |
| 13. | Daniel Ski M, Izizler TA, McMonagle E, Kane JC, Pupin L, Morrow J. Linkage of hypoalbumiunia, inflammation, and oxidative stress in patients receiving maintenance hemodialysis therapy. Am J Kidney Dis 2003;42(2):286-94. |
| 14. | Owen WF, Lowrie EG. C-reactive protein as a outcome predictor for maintenance hemodialysis patients. Kidney Int 1988;54:627-36. |
| 15. | Ortega O, Rodriguez I, Gallar P, et al. Significance of high C-reactive protein levels in predialysis patients. Nephrol Dial Transplant 2002;17:1105-9. [PUBMED] [FULLTEXT] |
| 16. | Menon V, Wang X, Green T, Beck GJ, Kusek JW, Marcovina SM. Relationship between Creactive protein, albumen, and cardiovascular disease in patients with chronic kidney disease. Am J Kidney Dis 2003;42:44-52. |
Correspondence Address:
Georgi Abraham
Department of Internal Medicine, SRMC, Porur, Chennai, Tamil Nadu
India
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PMID: 19736479 
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