Kidney Fibrosis Biomarkers in Type 2 Diabetes Treated with Dulaglutide

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Tuttle K. R., Wilson J. M., Lin Y., Hui-Rong Qian H-R, Federica Genovese, Karsdal M. A., Duffin K. L., Botros Fady T.: Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide. American Journal of Nephrology DOI 10.1159/000529374

Kidney fibrosis is one of the final common end-points of progressive CKD in both diabetic and non-diabetic patients. But very few studies have attempted to evaluate kidney fibrosis and its progression using potential serum and/or urine biomarkers. This is an important and understudied aspect of CKD progression. 

Tuttle and coworkers studied two fibrosis biomarkers (not necessarily kidney-specific); namely, serum Pro-C6 (a measure of Collagen Type VI production) and urine C3M (a measure of Collagen Type III degradation) in a post-hoc analysis of a therapeutic trial comparing once weekly Dulaglutide (A GLP1R agonist) compared to Insulin Glargine for up to one year in subjects with Type 2 Diabetes and CKD (eGFR >15 and <60ml/min/1.73m2). 

Dulaglutide therapy decreased serum Pro-C6 and increased urine C3M levels compared to insulin glargine. Serum levels of Pro-C6 were negatively correlated. Dulaglutide decreased the rate of eGFR decline compared to Insulin glasgine the change of eGFR over time and the levels of urine C3M were positively correlated with the change in eGFR over time. 

No repeat kidney biopsies were performed to validate changes in kidney fibrosis.  There were no untreated (or metformin treated  only controls.  And as these biomarkers are not kidney specific, extra renal effects are possible. Reverse causality is another possible explanation, as correlation is not proof of causality. Nevertheless, these studies invoke the hypothesis that a GLP1R agonist may lead to a decrease in kidney fibrosis and thereby exert reno-protective effects. Further studies are warranted, especially those involving sequential kidney biopsies and/or non-invasive means of directly assessing the rate of kidney fibrosis. 

Richard Glassock

Quoted Karger Article

Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide