CKD273 demonstrates benefit of SGLT2 inhibition: link to reducing fibrosis

Nov. 2022

The effect of the sodium–glucose cotransporter 2 (SGLT-2) inhibitor Dapagliflozin was evaluated on the kidney-risk urinary proteomic classifier (CKD273) in persons with type 2 diabetes (T2D) and albuminuria.

In a double-blind, randomized, controlled, crossover trial, we assigned participants with T2D and urinary albumin to creatinine ratio (UACR) ≥30 mg/g to receive dapagliflozin or matching placebo added to guideline-recommended treatment ( identifier NCT02914691). Treatment periods lasted 12 weeks, when crossover to the opposing treatment occurred. The primary outcome was change in CKD273 score. Secondary outcomes included regression from high-risk to low-risk CKD273 pattern using the prespecified cutoff score of 0.154. The primary outcome was assessed using paired t test between end-to-end CKD273 scores after dapagliflozin and placebo treatment. The McNemar test was used to assess regression in risk category.

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

Dapagliflozin added to renin-angiotensin system inhibition reduced the urinary proteomic classifier CKD273 in persons with T2D and albuminuria, paving the way for the further investigation of CKD273 as a modifiable kidney risk factor.

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