Urinary Podocalyxin as a Candidate Biomarker for Early Diabetic Nephropathy: Findings from a Cross-sectional Study

Introduction: Diabetic nephropathy is the leading cause of end-stage renal disease in diabetic patients.Although microalbuminuria is used to screen diabetic nephropathy currently, studies document structural changes in renal glomerulus even in normoalbuminuric diabetic patients.Also, recent studies suggest that even a minimal detectable level of albumin in urine is associated with an increased risk of overt nephropathy.Hence there is a need for more sensitive and specific biomarkers for early diabetic nephropathy.Evidence shows that one of the earliest changes in diabetic nephropathy includes structural and functional alterations in glomerular podocytes.During podocyte injury, podocyte-expressed proteins are shed in urine.Podocalyxin is a CD-34-related sialomucin protein, highly expressed by podocytes.Recent studies show an increase in urinary podocalyxin (U.PLX) levels in diabetic patients when compared to healthy subjects, even before the appearance of microalbuminuria. Objectives: To compare the U. PLX level in type 2 diabetes mellitus (T2DM) patients with microalbuminuria, without microalbuminuria, and healthy subjects. To study the correlation of urine podocalyxin with urine albumin in T2DM patients.Materials and methods: In this hospital-based cross-sectional study, 30 type 2 diabetic patients aged between 30 and 70 years with microalbuminuria and 30 without microalbuminuria, attending the Endocrinology outpatient department (OPD), Government Medical College, Thiruvananthapuram, and 30 healthy controls were consecutively recruited.A preformed questionnaire was given to them.Biochemical parameters like urine creatinine were analyzed in a fully automated analyzer.Urine podocalyxin and albumin were assessed by the enzyme-linked immunosorbent assay (ELISA) method.Mean SD was used to express normally distributed variables, and median (IQR) was used for non-normally distributed variables.Analysis of variance (ANOVA) or the Kruskal-Wallis test was appropriately performed to compare the estimates of variables among the study groups.The Spearman's rank correlation analysis was performed to assess the relationship between U. PLX and other clinical parameters.A p-value < 0.05 indicates a statistically significant correlation.Results: The mean U. PLX level was highest in the microalbuminuric group (78.4 7.1 ng/mL), followed by the normoalbuminuric group (72.7 6.6 ng/mL), and lowest in the healthy controls (65 6.5 ng/mL).Urinary podocalyxin levels were significantly increased in diabetic patients without microalbuminuria compared to controls, and further elevated in those with microalbuminuria.There is a significant positive correlation between U. PLX and urine albumin in diabetic patients as renal impairment progresses.Conclusion: Renal podocyte damage occurs in diabetic patients even before the onset of microalbuminuria, and its progression, as indicated by increased U. PLX levels, is associated with worsening albuminuria.Therefore, U. PLX could, be used as an early noninvasive biomarker of diabetic nephropathy.