Kidney Week

Abstract: FR-PO321

Assessing Heterogeneity of Treatment Effects from Canagliflozin (CANA) on Kidney Outcomes Using the Joslin Kidney Panel: Insights from the CREDENCE Trial

Session Information

• Diabetic Kidney Disease: Clinical Modeling, Diagnosis, Education, and More
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Tye, Sok Cin, Joslin Diabetes Center, Boston, Massachusetts, United States

Sok Cin Tye, PhD

• Md Dom, Zaipul, Joslin Diabetes Center, Boston, Massachusetts, United States

Zaipul Md Dom, PhD

• Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States

Eiichiro Satake, MD, PhD

• Hansen, Michael K., Janssen Research & Development, LLC, Springhouse, Pennsylvania, United States

Michael K. Hansen, PhD

• Breyer, Matthew Douglas, Janssen Research & Development, LLC, Springhouse, Pennsylvania, United States

Matthew Douglas Breyer, MD, FASN

• Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States

Andrzej S. Krolewski, MD, PhD

Background

SGLT2 inhibitors reduce kidney outcomes among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The Joslin Kidney Panel of 21 proteins (JKP) predicts end-stage kidney disease (ESKD) in patients with diabetes.¹ This study aims to develop a JKP-based risk model and assess heterogeneity of treatment effects (HTE) in patients with T2D and CKD.

Methods

Post-hoc analysis of the CREDENCE trial, including 1374 participants with CKD stage 3. Baseline JKP protein levels measured via Olink® platform. The kidney outcome studied was first occurrence of estimated glomerular filtration rate (eGFR) decline by 50% or ESKD. A Cox proportional hazard model was used to first derive a clinical markers model with four predictors from the Kidney Failure Risk Equation. Next, JKP was integrated and final model selected using a stepwise Akaike’s Information Criterion. Participants classified into risk quartiles (Q1-Q4), with event rates, relative risks, and cumulative incidence (CI) differences estimated.

Results

During 2.6 years follow-up, 155 (placebo) and 82 (CANA) kidney events recorded. The final model, comprising age, sex, eGFR, urinary-albumin-creatinine-ratio, and six JKP proteins, yielded a C index of 0.82 (95% CI 0.77 to 0.87). Estimated median baseline risk was 20.9% (IQR 8.6%-47.0), demonstrating considerable variation among individual patients. Notably, ~50% of patients (N=688) in this study with a lower predicted risk (Q1,Q2) did not benefit from CANA. However, those in the higher risk quartiles showed a substantial relative treatment benefit with hazard ratios (HR) of 0.35 (95% CI 0.19 to 0.66) and HR 0.42 (95% CI 0.30 to 0.59) in Q3 and Q4 respectively. They also had greatest absolute benefit of CANA, shown by a notable CI rate difference. (Table 1)

Conclusion

Integrating the JKP into the risk stratification model improves the prediction of kidney outcomes among patients with T2D and CKD. HTE was observed among CANA-treated patients, with those at higher baseline risk benefiting the most

Funding

• NIDDK Support