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Abstract: TH-PO232

Application of the Joslin Kidney Panel Using a Proximity Extension Assay: From Prognostics to Precision Medicine

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Md Dom, Zaipul I, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Rashidi, Narges M., Olink Proteomics, Watertown, Massachusetts, United States
  • Looker, Helen C., National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, United States
  • Morieri, Mario Luca, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Krolewski, Bozena, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Ricca, Joseph, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Nelson, Robert G., National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, United States
  • Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Doria, Alessandro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

The Joslin Kidney Panel (JKP) of 21 circulating proteins is associated with increased risk of ESKD in patients with diabetes (Kobayashi et al. KI 2022). We evaluated the JKP as a tool for assessing prognosis in 4 diverse clinical settings.

Methods

Concentrations of the JKP proteins were measured in 4 cohorts on a custom-made OLINK platform using a proximity extension assay. Prognostic value of the JKP proteins for eGFR slope and ESKD during 7-15 years of follow-up was examined in 60 Joslin Kidney Study patients with T1D; for 10-year risk of ESKD in a cohort of 162 Pima Indians with T2D; and for predicting the beneficial effect of fenofibrate in 450 ACCORD trial participants. In addition, the effect of the JAK1/2 inhibitor, Baricitinib, on the 1-year changes of the JKP proteins was examined in 42 Baricitinib trial participants (25 placebo/17 Baricitinib).

Results

In the Joslin cohort, baseline levels of all proteins correlated strongly with eGFR slope (r= -0.4 to -0.7; p<10-7) (Fig. 1A for KIM1) and all were significantly higher in patients who developed ESKD than in those who did not (FC=1.3-5.4; p<10-8) (Fig. 1B for TNF-RSF1A). In the Pima cohort, baseline levels of 20 proteins were associated with ESKD risk in univariable logistic model (ORs =1.7-4.2; p<10-7) (Fig. 1C) and the ORs remained significant for 19 proteins (excluding WFDC2 and PI3) after adjustment for key confounders. Fenofibrate treatment reduced loss of kidney function in ACCORD patients who had levels of two proteins above the median (Fig. 1D). Baricitinib significantly decreased levels of 5 proteins relative to placebo (Fig. 1E for TNF-RSF7 and IL-1RT1).

Conclusion

The JKP successfully identified patients at risk of progressive kidney disease and those with beneficial responses to specific reno-protective therapies.

Funding

  • NIDDK Support