Can Endostatin Predict Renal Risk in Type 2 Diabetes?

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Plasma endostatin might provide a useful biomarker of the risk of renal dysfunction in patients with type 2 diabetes, according to a study in Kidney International.

The study included banked specimens from 374 participants (187 matched cases and controls) from the Action to Control Cardiovascular Disease (ACCORD) trial as well as samples from a contemporary cohort of 871 patients with type 2 diabetes from the Mount Sinai BioMe Biobank. Plasma endostatin – a fragment of collagen XVIII that may reflect endothelial dysfunction, matrix remodeling after kidney injury, and angiogenesis – was evaluated for association with a composite outcome of 40% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease.

Participants who met the composite renal outcome had higher baseline plasma endostatin levels. Log2-transformed endostatin levels were associated with similar and significant increases in risk in both groups: adjusted odds ratio 2.5 in ACCORD and hazard ratio 2.6 in BioMe. Risk was also elevated for those in the highest versus lowest quartile of plasma endostatin: OR 3.6 in ACCORD and HR 4.4 in BioMe.

In the BioMe data, adding information on endostatin to a baseline clinical model improved the area under the curve for the composite renal outcome from 0.74 to 0.77. At a cutoff of 45 ng/mL, corresponding to the fourth quartile value, elevated plasma endostatin had a sensitivity of 50%, specificity of 71%, and positive and negative predictive value of 21% and 90%, respectively.

New biomarkers are needed to predict renal function decline associated with type 2 diabetes, particularly in patients with preserved GFR at baseline. This study suggests that plasma endostatin is associated with decline in kidney function over time in patients with type 2 diabetes.

Added to conventional predictors, plasma endostatin may improve risk discrimination for declining renal function. The investigators highlight the need for further validation, as well as studies to determine whether early assessment of diabetic kidney disease risk using plasma endostatin can improve clinical care [Chauhan K, et al. Plasma endostatin predicts kidney outcomes in patients with type 2 diabetes. Kidney Int 2019; DOI: 10.1016/j.kint.2018.09.019].