Abstract: FR-OR037
Tirzepatide Reduces Rapid Kidney Function Decline in Patients with Type 2 Diabetes, CKD Stage 3, and Elevated Apoptotic Proteins
Session Information
- Exciting Developments in CKD Research: From Diagnostics to Management and More
October 23, 2026 | Location: Mile High Ballroom 1D, Convention Center
Abstract Time: 04:30 PM - 04:40 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
- Tye, Sok Cin, Joslin Diabetes Center, Boston, Massachusetts, United States
- Pavo, Imre, Eli Lilly and Company, Indianapolis, Indiana, United States
- Nowak-Szwed, Anna, Joslin Diabetes Center, Boston, Massachusetts, United States
- Apostadero, Aaron, Joslin Diabetes Center, Boston, Massachusetts, United States
- Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
- Fleming, Fergus, Renalytix AI Inc, New York, New York, United States
- Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
Tirzepatide (TZP) has renoprotective effects in type 2 diabetes (T2D), but treatment response varies among patients. In this study, we investigated whether baseline plasma levels of 21 Joslin Kidney Panel (JKP) proteins identify patients with the greatest kidney benefit from TZP treatment and provide insight into underlying mechanisms.
Methods
The 21 JKP proteins were previously identified as strong predictors of end-stage kidney disease (ESKD) risk in diabetes (Krolewski et al., CJASN 2026). Now, we measured them in plasma of 220 T2D patients with chronic kidney disease (CKD) stage 3 at the baseline of the SURPASS-4 trial using the Joslin-OLINK platform. Participants received TZP (5 - 15 mg weekly) (n=107) or insulin glargine daily (n=113), the mean follow-up period was 24 months. The primary outcome was rapid kidney function decline (eGFR slope ≤ -5.0 mL/min/year). Treatment effects of TZP were evaluated across protein concentration tertiles.
Results
TZP treatment significantly reduced the prevalence of rapid kidney function decline compared with insulin glargine (5 vs. 13%, respectively). The beneficial effect was strongly dependent on[A1] [SE2] baseline plasma levels of 12 JKP proteins (TNF-R1, TNF-R3, TNF-R6B, TNF-R7, TNF-R10B, TNF-R11A, TNF-R27, CD160, IL-1RT1, EFNA4, EPHA2, LRP11), most of which were related to apoptosis (Ihara et al., JCI Insight 2024). The risk reduction was observed primarily in patients with the highest protein concentrations, with little or no benefit in the lower tertiles. TNF receptor 10B (death receptor) is presented as a representative JKP protein (Figure). The apoptosis-related proteins from JKP outperformed clinical variables in discriminating the renoprotective response to TZP.
Conclusion
Higher baseline levels of apoptosis-related JKP proteins identified patients with the highest renal benefit from TZP, supporting their potential utility for treatment personalization. The greater benefit observed in this subgroup also suggests that modulation of apoptotic pathways may contribute to the therapeutic effects of TZP.
Figure. Rapid kidney decline by TNF-R10B tertiles.
Funding
- NIDDK Support – Eli Lilly and Company, and Renalytix AI Inc