American Diabetes Association
Supplemental_information_12JUL2022_clean.pdf (324.72 kB)

Dapagliflozin improves the urinary proteomic kidney risk classifier CKD273 in type 2 diabetes with albuminuria – a randomized clinical trial

Download (324.72 kB)
posted on 2022-08-23, 18:59 authored by Viktor Rotbain Curovic, Mie Klessen Eickhoff, Teemu Rönkkö, Marie Frimodt-Møller, Tine Willum Hansen, Harald Mischak, Peter Rossing, Tarun Singh Ahluwalia, Frederik Persson


Objective: To evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin, on the kidney risk urinary proteomic classifier (CKD273), in persons with type 2 diabetes and albuminuria.

Research Design and Methods: In a double-blind randomized controlled crossover trial we assigned participants with type 2 diabetes and urinary albumin-creatinine ratio (UACR) ≥30 mg/g to receive dapagliflozin or matching placebo added to guideline recommended treatment (NCT02914691). Treatment periods lasted 12 weeks at which crossover to opposing treatment occurred. The primary outcome was change in CKD273 score. Secondary outcomes include regression from high-risk to low-risk CKD273 pattern using the pre-specified cut-off score of 0.154. The primary outcome was assessed using paired t-test between end-to-end CKD273 levels after dapagliflozin and placebo treatment. McNemar’s test was used to assess regression in risk category.

Results: A total of 40 participants were randomized and 32 completed the trial with intact proteomic measurements. Twenty-eight (88%) were male, the baseline mean (standard deviation) age was 63.0 (8.3) years, mean diabetes duration was 15.4 (4.5) years, mean HbA1c was 73 (14) mmol/mol (8.8 (1.3) %) and median (inter-quartile range) UACR was 154 (94, 329) mg/g. Dapagliflozin significantly lowered CKD273 score compared to placebo (-0.221, 95%CI: -0.356, -0.087, p=0.002). Fourteen participants exhibited a high-risk pattern after dapagliflozin treatment compared to 24 after placebo (p=0.021). 

Conclusions: Dapagliflozin added to renin-angiotensin system inhibition reduced the urinary proteomic classifier CKD273 in persons with type 2 diabetes and albuminuria paving the way for the further investigation of CKD273 as a modifiable kidney risk factor. 


The study was supported by AstraZeneca. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.