Association of Inflammatory Marker C-Reactive Protein and Interleukin-6 with Stages 3-5 of Chronic Kidney Disease

Abstract

Background: Despite different strategy to retard the progression of CKD, majority still progress to ESRD. Other than conventional risk factors inflammation is considered as one of the reversible factors responsible for CKD progression which can be intervened. Therefore, we have studied the level of inflammatory marker CRP and IL-6 at stages 3-5 of CKD patients and their association with CKD stage progression determined by eGFR. Methods: We have conducted a cross sectional study among 150 CKD patients and 32 healthy controls at OPD of Nephrology department of National Institute of Kidney Diseases and Urology, Dhaka from January`2016 to December`2016. Purposive sampling method was the tool for case selection and CKD was defined as eGFR <60ml/min/1.73m2. AKI, history of dialysis, kidney transplant, patients having acute infection, malignancy or liver disease, received chemotherapy or immunotherapy (<6 months) and patients with connective tissue disease were the exclusion criteria. Fasting blood glucose, Hb%, serum Ca++, serum PO4, serum total cholesterol and serum triglyceride level were measured for both case and controls. eGFR has been calculated using MDRD equation. For the cases CRP had been measured on two occasions at an interval of one and half month. Those cases who had raised CRP level in both occasions were selected for measurement of IL-6 from second sample. CRP had been measured by turbidimetry method using fully automated chemistry analyzer. IL-6 had been measured using enzyme linked immunosorbent assay (ELISA) based on the Biotin double antibody sandwich technology. Scatter diagram and multiple regression models were used to examine the association between CRP and IL-6 with stage 3-5 of CKD denoted by eGFR. Results: The mean of CRP were 9.5±2.7 mg/L in CKD patients vs. 2.9±0.5 mg/L in controls without CKD and the mean of IL-6 were 29.5±13.0 pg/ml in CKD patients vs. 3.3±0.3 pg/ml in controls without CKD. Both were elevated and significant statistically (p=.001). Scatter diagram showing correlation coefficient (r value) -0.592 and -0.615 for eGFR vs. CRP and eGFR vs. IL-6 respectively which indicate both are negatively correlated with eGFR. But IL-6 had a more strong negative correlation. Multiple regression analysis shows regression co efficient (B) for CRP and IL-6 is -1.251 and -2.826 respectively after taking into account other factors which can alter eGFR level (age, Hb%, serum Calcium, S. Total Cholesterol, S.PO4, S. Triglyceride) that indicates in the prediction of eGFR, IL-6 had significant negative association than CRP after adjusting the conventional factors responsible for CKD progression. Conclusion: Our data suggest that though CRP and IL-6 both are significantly raised in advanced CKD stage 3-5, IL-6 is more rapidly increasing and more strongly associated than CRP with the severity of CKD measured by eGFR.