Original Investigation Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney Disease Tara I. Chang,1 Guo Wei,2,3 Robert Boucher,2 Holly Kramer,4,5 Glenn M. Chertow,1 Alfred K. Cheung,2,6 Tom Greene,3 Paul K. Whelton,7 and Srinivasan Beddhu2,6 Abstract Background We sought to determine whether intensive systolic BP (SBP) lowering was harmful in Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD (eGFR,60 ml/min per 1.73 m2) and lower baseline diastolic BP (DBP). Methods We related baseline DBP with the SPRINT primary composite end point (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or cardiovascular death) and all-cause death. We examined the effect of intensive SBP lowering on these outcomes across the range of baseline DBPs using Cox regression with treatment by baseline DBP interaction terms. Results Among 2646 SPRINT participants with CKD, lower baseline DBP was associated with a higher adjusted hazard of the primary composite end point and all-cause death. For example, participants with baseline DBP of 61 mm Hg (mean baseline DBP in the lowest tertile) experienced a 37% (95% CI, 7% to 75%) higher hazard of the primary outcome relative to participants with baseline DBP of 75 mm Hg (mean baseline DBP for overall). The benefit of intensive SBP lowering was consistent across a range of baseline DBPs on rates of the primary composite end point (linear interaction P value 50.56) and all-cause death (linear interaction P value 50.20). Conclusions Among SPRINT participants with baseline CKD, lower DBP was associated with higher rates of the primary composite end point and all-cause death. However, DBP did not seem to modify the benefit of intensive SBP lowering on the primary composite end point or all-cause death. Our results suggest that lower DBP should not necessarily impede more intensive SBP lowering in patients with mild to moderate CKD. KIDNEY360 1: 368–375, 2020. doi: https://doi.org/10.34067/KID.0000982019 Introduction Coronary perfusion primarily occurs during diastole, and intensive systolic BP (SBP) lowering often leads to diastolic BP (DBP) lowering. In observational ontreatment analyses, lower DBP is associated with an increased risk of cardiovascular disease events and death in patients at higher risk for cardiovascular events (1–4). Concern related to DBP lowering may be of particular relevance among patients with CKD given the higher prevalence of elevated SBP and lower DBP in that population due in part to known associations of CKD with premature vascular aging and vascular stiffness (5,6). A recent analysis of data from the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a U-curve relationship between baseline DBP and the primary outcome and all-cause death, in which participants with the lowest baseline DBP had the higher risk of adverse clinical events (7). However, comparison of randomized groups demonstrated that intensive SBP treatment reduced the risk of the primary outcome and all-cause death at every level of baseline DBP, including among participants with the lowest levels of baseline DBP. We sought to determine whether the effects of intensive SBP lowering in participants with CKD differed by baseline DBP and specifically, 1 Division of Nephrology, Stanford University, Palo Alto, California 2 Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, Utah 3 Division of Biostatistics, Departments of Population Health Sciences and Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 4 Department of Public Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois 5 Medical Service, Hines Veterans Affairs Medical Center, Hines, Illinois 6 Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah 7 Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana Correspondence: Srinivasan Beddhu, University of Utah School of Medicine, 85 North Medical Drive E, Room 201, Salt Lake City, UT 84112. Email: Srinivasan.Beddhu@hsc.utah.edu 368 Copyright © 2020 by the American Society of Nephrology www.kidney360.org Vol 1 May, 2020 whether intensive SBP lowering was harmful in participants with CKD and lower baseline DBP. Materials and Methods The SPRINT was a multicenter, randomized outcome trial sponsored by the National Institutes of Health comparing the effects of intensive versus standard SBP lowering on cardiovascular and other outcomes, including all-cause death, kidney disease, dementia, and cognitive impairment (8–10). Study