OBJECTIVES/GOALS: Renal vascular resistance (RVR) is the opposition to blood flow by renal arteries. At the population level, dietary salt increases RVR and blood pressure (BP), which are associated with cardiovascular disease. Recent data indicate exogenous ketones may offset adverse cardiorenal effects of salt. METHODS/STUDY POPULATION: Our registered clinical trial (NCT05545501) is a double-blinded, placebo-controlled, crossover study. Participants are being randomized to three 10-day conditions: A) control; B) high salt; C) high salt and ketone supplementation. Ten participants are enrolled (target 30 participants). Renal blood velocity (RBV) in the renal and segmental arteries will be measured in the decubitus position using Doppler ultrasound during a 3-minute baseline and 3-minute cold pressor test. We will measure brachial BP with an automated oscillometric BP monitor. RVR will be calculated as mean BP divided by RBV. Statistical analyses will include ANOVA and correlations with α set at ≤ 0.05. RESULTS/ANTICIPATED RESULTS: We anticipate attenuated RBV and increased BP during the cold pressor test, particularly following high salt loading, leading to greater RVR. We hypothesize ketone supplementation will attenuate the high salt induced increase in RVR during the cold pressor test. In addition to RVR we will examine renal vascular conductance which is the ease with which blood flows through arteries, calculated as RBV divided by mean BP. Additional hemodynamics such as heart rate and systolic and diastolic BP will be reported and correlated with primary outcomes. DISCUSSION/SIGNIFICANCE: Dietary salt plays a role in hypertension, cardiovascular disease, and chronic kidney disease, which are leading causes of death. Ketone supplementation may be a promising approach to counteract the detrimental effects of high dietary salt and improve cardiovascular health in adults.