#900 Endotrophin is associated with long-term risk of kidney function decline in normoalbuminuric persons with type 2 diabetes in the Joslin Kidney Study

Abstract

Abstract Background and Aims Endotrophin is a pro-fibrotic and pro-inflammatory molecule derived from the post-translational processing of type VI collagen. Evidence for an association of increased circulating levels of endotrophin with increased risk of kidney and cardiovascular-related outcome and all-cause mortality in persons with type 2 diabetes have recently emerged. Here we want to investigate endotrophin as an early marker of kidney-related outcome risk in persons with type 2 diabetes with normal levels of albuminuria. Method Endotrophin was measured using the nordicPRO-C6TM assay (Nordic Bioscience, Herlev, Denmark) in serum of 1088 individuals with type 2 diabetes from the Joslin Diabetes Study. 635 individuals had normal to mildly increased albuminuria (<30 mg/g), 379 had moderately increased albuminuria (30-300 mg/g) and 74 had severely increased albuminuria (>300 mg/g). All patients had eGFR >60 and where hence classified as CKD stage 1 and 2. Risk of kidney disease progression was defined as a 40% decline in eGFR within 10 years. Results In the cohort (n = 1088), a total of 128 patients progressed to 40% eGFR decline. High levels of circulating endotrophin were associated with an increased risk of kidney disease progression in unadjusted logistic regression analysis (OR for T3 vs T1+T2 (PRO-C6): 2.1 [95% CI: 1.4-3.0], p = 0.0001) and after adjustment for eGFR, HbA1c, age and sex (OR for T3 vs T1+T2 (PRO-C6): 1.8 [95% CI: 1.1-2.6], p = 0.005). When looking at patients classified in albuminuria stages, endotrophin was significantly associated with kidney disease progression in the individuals with normal to mildly increased albuminuria (39 events) (OR for T3 vs T1+T2 (PRO-C6): 2.6 [95% CI: 1.3-4.9], p = 0.005 in unadjusted analysis and 2.3 [95% CI: 1.1-4.5], p = 0.02 after adjustment for eGFR, HbA1c, age and sex, but it was not significantly associated to kidney progression in the groups with moderately (49 events) and severely (40 events) increased albuminuria. Conclusion This study sheds further light on the potential of endotrophin as an early marker of long-term adverse kidney outcome in persons with type 2 diabetes. The association of circulating endotrophin with increased risk of kidney disease progression had already been reported both in CKD and DKD patients (for shorter-term outcome), and this study further expands on the applicability of endotrophin as a biomarker in persons with type 2 diabetes without an overt kidney disease, who will nevertheless progress to develop CKD in a 10-year time horizon.