Ischaemia-modified Albumin Estimation and Usefulness of Different Albumin Adjustment as a Marker to Predict Kidney Damage in Diabetes Mellitus

Abstract

Introduction: Urine Albumin Creatinine Ratio (UACR) has been the standard for detecting albuminuria in diabetes mellitus, but the presence of “non albuminuric renal impairment” has encouraged the search for novel markers. Recently, increased serum Ischaemia Modified Albumin (IMA) levels have been implicated in cases of Diabetic Nephropathy (DN). However, its estimation by conventional albumin cobalt assay is confounded by serum albumin levels. Aim: To estimate IMA and albumin-adjusted IMA levels to assess their utility in diagnosing early renal damage in diabetes mellitus. Materials and Methods: This hospital-based cross-sectional study was conducted from March 2014 to January 2015 at Kasturba Medical College, Mangaluru, Karnataka, India. The study included 30 healthy individuals and 60 patients with diabetes mellitus, which were further divided equally into three groups based on UACR. The groups were as follows: normoalbuminuria group (UACR <30 mg/g of creatinine), microalbuminuria group, and macroalbuminuria group (UACR 30-300 and >300 mg/g of creatinine, respectively). Serum IMA levels were estimated using Enzyme-linked Immunosorbent Assay (ELISA), while Glycated Haemoglobin (HbA1c), serum creatinine, urine albumin, and urine creatinine were measured using auto-analysers. Albumin-adjusted IMA values were measured, and correlation assays between IMA and serum albumin concentration were analysed in each group using oneway Analysis of Variance (ANOVA) and Pearson’s correlation. Results: In the present study, out of the 60 diabetes mellitus patients, 27 were females and 33 were males, with a mean age of 53±17 years. Among the 30 controls, 14 were females and 16 were males, with a mean age of 51±17.5 years. Serum albumin had a significant negative correlation with IMA in the microalbuminuria (r=-0.4, p<0.01) and macroalbuminuria (r=- 0.58, p<0.001) groups. A significant mean difference was found in serum IMA, albumin-adjusted IMA, IMA index, and IMA ratio between the normoalbuminuria group and the other groups. Receiver operating characteristic analysis was used to predict the early stage of nephropathy (albuminuria). High sensitivity and specificity were measured for IMA (97.5% and 78%, respectively) and IMA ratio (97.5% and 76%, respectively) at cut-off percentages of 99 and 24.5, respectively. Conclusion: The IMA ratio has greater diagnostic importance compared to other adjusted IMA values in discriminating diabetic patients with micro- and normoalbuminuria.