Urinary transglutaminase 2 as a potential biomarker of chronic kidney disease detection and progression

Abstract

BackgroundThis study aimed to determine whether urinary transglutaminase 2 (TG2) has the potential to act as an early biomarker of chronic kidney disease (CKD) and whether it can predict the rate of progression better than can albuminuria. MethodsUrine samples were collected prospectively from 292 patients with CKD at the Sheffield Kidney Institute and 33 controls and followed for a minimum of 3 years. The cohort consisted of 61·7% men of whom 89% were white. Major causes of CKD were: diabetic nephropathy (29·05%), chronic glomerulonephritis (23·01%), hypertensive nephrosclerosis (16·6%), atherosclerotic renovascular disease (8·3%), chronic interstitial nephritis (6·41%), and autosomal dominant polycystic kidney disease (4·52%). Urinary TG2 was measured by an in-house sandwich ELISA. One-way ANOVA with Bonferroni correction was applied to estimate differences between groups. Area under the curve for receiver operating characteristic (ROC) analysis was used to determine prediction accuracy. A p value of less than 0·05 was considered statistically significant. FindingsUrine TG2 was 41 times higher in CKD patients than in healthy individuals (mean 3381 ng/mL [SD 135·36] vs 81·6 [4·18], p<0·001). Levels were elevated 17 fold by CKD stage 2. The largest increase in urine TG2 was observed in patients with diabetic nephropathy (7005 ng/mL [376]) with a 85-fold rise in CKD compared with healthy individuals, followed by hypertensive nephrosclerosis (3899 ng/mL [277]). TG2:creatinine ratio was 9·72 ng/mmoL [1·29] in controls versus 605·77 ng/mmoL [81·07] in patients with CKD (p<0·001). TG2 excretion was elevated in those patients with progressive (estimated glomerular fitration rate decline 2–5 mL/min/1·73m2 per year, 8997·91 ng/mL) or rapidly progressive CKD (>5 mL/min/year, 17650·195 ng/mL) compared with non-progressors (<2 mL/min/1·73m2 per year, 2764 ng/mL; p>0·05). There was no correlation between TG2 and total proteinuria (r=0·02808, 95% CI −0·09814 to 0·1534; p=0·6632). ROC curve analysis determined an 81·1% accurate prediction of progression for the TG2:creatinine ratio compared with just 71·4% for the albumin:creatinine ratio. InterpretationUrinary TG2 was significantly increased in all causes of CKD. ROC curve analysis demonstrated that TG2:creatinine ratio is a better predictor of patients with progressive CKD than albumin:creatinine ratio indicating its potential as a non-invasive biomarker of progressive kidney scarring. FundingUniversity of Sheffield and Pfizer.