Objective: Evaluating effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on the urinary CKD273 proteomic score in patients with type 2 diabetes (T2D) and albuminuria.
Methods: A double-blinded, randomized, placebo-controlled, crossover trial of 12 weeks dapagliflozin (10 mg) or matching placebo added to standard care. Patients included (n=40) had T2D and albuminuria (UACR≥30 mg/g). At baseline and end of treatment periods HbA1C was measured, spot urine for urinary proteomics and three consecutive morning spot urines for albuminuria were collected and 24h blood pressure and 51Cr-EDTA (GFR) were performed. Urine proteomic patterns was evaluated using the CKD273 score. To determine high-risk or low risk of diabetic kidney disease a previously defined cut off of 0.154 was used. Results were compared using mixed model analysis adjusted for age, sex, systolic blood pressure, HbA1c, albuminuria and GFR. Chi-square analysis was used to examine change in risk category based on proteomics.
Results: Baseline values for the 36 participants completing the study: Geometric mean urinary albumin creatinine ratio (UACR) = 147 (IQR 82-330) mg/g, mean eGFR = 84 ml/minute/1.73 m2 (SD±19.3), HbA1c = 73 mmol/mol (SD±15) and 24h blood pressure = 147/82 mmHg (SD±12.0/8.1). Dapagliflozin reduced UACR by 44% (95% CI 17-78%, p<0.01), GFR by 10.6 (6-15) ml/minute/1.73m2 (p<0.01), HbA1c by 7.4 (5-10) mmol/mol (p<0.01) and 24h blood pressure by 4.1/2.9 mmHg (p=0.058/p<0.01). The CKD273 proteomic score improved from mean 0.457 with -0.217 (p<0.01) and renal risk category improved from 72% at high risk to 47% after dapagliflozin (p=0.032).
Conclusions: Dapagliflozin added to standard care in T2D patients with albuminuria significantly reduced the urinary CKD273 proteomic score and renal risk. This indicates a possible direct beneficial effect on the kidneys, which may explain part of the renal benefit of SGLT2i seen in clinical trials.
F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.K. Eickhoff: None. H. Mischak: Stock/Shareholder; Self; Mosaiques Diagnostics. M. Frimodt-Moller: None. P. Rossing: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. Other Relationship; Self; Novartis AG, Novo Nordisk A/S.