Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial
Authors' conclusion
The renoprotective effects of canagliflozin in patients at a high risk of ESKD can be significantly explained by changes in RBC variables and UACR. The complementary mediating effects of RBC variables and UACR may support the renoprotective effect of canagliflozin in different patient groups.
Study context
- Population
- Patients with T2D at high risk of end-stage kidney disease (ESKD)
- Comparison
- Canagliflozin; mediators of renoprotection
- Primary endpoint
- Renal outcome: composite of ESKD, serum creatinine doubling or renal death; percentage mediation of canagliflozin effect by 42 biomarkers
- Follow-up
- Mediator changes at 52 weeks
Methodological detailspost hoc analysis, mediation analysis
- Post hoc analysis
- Mediation analysis
Primary result
As reported in the abstract
Mediation of renal risk reduction with canagliflozin · 52 weeks
- Haematocrit change mediated
- 47%
- Haemoglobin change mediated
- 41%
- Red blood cell (RBC) count change mediated
- 40%
- Urinary albumin-to-creatinine ratio (UACR) change mediated
- 29%
- Combined haematocrit and UACR mediated
- 85%
Further findings
Mediation by haematocrit change, by UACR subgroup
- UACR >3000 mg/g
- 17%
- UACR ≤3000 mg/g
- 63%
Mediation by UACR change, UACR >3000 mg/g subgroup
- UACR change was the highest mediating factor
- 37%
- Driven by strong association between UACR decline and renal risk reduction
Original publication
Mediators between canagliflozin and renoprotection vary depending on patient characteristics: Insights from the CREDENCE trial. Diabetes Obes Metab. Published 29 June 2023. doi:10.
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