Volume 92, Issue 1, Pages 258-266 (July 2017) Improved clinical trial enrollment criterion to identify patients with diabetes at risk of end- stage renal disease  Masayuki Yamanouchi, Jan Skupien, Monika A. Niewczas, Adam M. Smiles, Alessandro Doria, Robert C. Stanton, Andrzej T. Galecki, Kevin L. Duffin, Nick Pullen, Matthew D. Breyer, Joseph V. Bonventre, James H. Warram, Andrzej S. Krolewski  Kidney International  Volume 92, Issue 1, Pages 258-266 (July 2017) DOI: 10.1016/j.kint.2017.02.010 Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 1 Prognostic cut-points derived from the multimarker analysis of the combined type 1 diabetes (T1D) and type 2 diabetes (T2D) cohorts. Plots of the cumulative risk of a study outcome within 3 years in T1D patients (solid line) and T2D patients (interrupted line). Sex, age, systolic blood pressure, hemoglobin A1c, estimated glomerular filtration rate, and tumor necrosis factor receptor (TNFR) 2 were included in the classification and regression tree analysis, but none surpassed the outcome separation achieved by TNFR1 and albumin-to-creatinine ratio (ACR). Letters (a), (b), and (c) in each plot refer to the corresponding areas in Figure 2. Kidney International 2017 92, 258-266DOI: (10.1016/j.kint.2017.02.010) Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 2 Distribution of patient outcomes in the combined study group (type 1 diabetes [T1D] and type 2 diabetes [T2D]) according to baseline values of tumor necrosis factor receptor (TNFR) 1 and albumin-to-creatinine ratio (ACR). Outcomes during the 3-year follow-up are color coded according to type: end-stage renal disease (ESRD) (red), 40% baseline estimated glomerular filtration rate (eGFR) loss (blue), deaths unrelated to ESRD (black ×), or no event (none) (open circle). The cut-points for TNFR1 (2.9 ng/ml and 4.3 ng/ml) and ACR (1900 mg/g) shown in Figure 1 are represented by interrupted horizontal and vertical lines, respectively. The dots within the areas labeled (a), (b), and (c) represent the patients in Figure 1 plots with the corresponding labels. The gray area indicates high risk, whereas the white area indicates a low risk of the outcome. Note that the distributions of blue and red dots closely overlap. Kidney International 2017 92, 258-266DOI: (10.1016/j.kint.2017.02.010) Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 3 Cumulative incidence of end-stage renal disease (ESRD) (interrupted line) and ESRD and deaths (solid line) in patients who are not eligible for a clinical trial according to the multimarker prognostic criterion. (a) Type 1 diabetes (T1D) patients (n = 160) and (b) type 2 diabetes (T2D) patients (n = 142). While the incidence of ESRD and mortality was low within the first 3 years, by the 10th year of follow-up, it reached 45% and 63% in T1D and T2D patients, respectively. Overall, during the 10 years of follow-up, 48 ESRD cases occurred in the T1D cohort and 38 in the T2D cohort that were not eligible by the multimarker criterion. Kidney International 2017 92, 258-266DOI: (10.1016/j.kint.2017.02.010) Copyright © 2017 International Society of Nephrology Terms and Conditions