Joslin Kidney Panel of circulating proteins predicting risk of ESKD as a precision medicine instrument.

To facilitate translational research on diabetic kidney disease, we developed the Joslin Kidney Panel (JKP), a panel of 21 circulating proteins strongly associated with risk of kidney function decline and progression to ESKD. Using a custom-made OLINK multiplex platform of assays with excellent specificity, precision, and accuracy, we quantified 21 JKP proteins in four independent study groups. In the Type 1 diabetes individuals from Joslin (n=59), FinnDiane (n=389) and Steno (n=283), JKP proteins predicted progression to ESKD during 10-year follow-up. Many of these proteins had prognostic performance equal to or better than clinical markers. An optimal model to predict risk of ESKD, which included clinical markers and 8 JKP proteins, was developed for the FinnDiane cohort and validated in the Steno cohort, and had better discrimination than the clinical model alone. By measuring baseline serum concentrations of the JKP proteins in a subgroup of 500 Type 2 diabetes individuals from the ACCORD trial, we identified 3 proteins that predicted amelioration of fast kidney function decline during 6 years of follow-up in those receiving treatment with fenofibrate. In conclusion, 21 JKP proteins measured on the Joslin OLINK platform provided a precision medicine-based approach to identify those at risk of ESKD and those responding to specific reno-protective therapy.