Targeting the Pathophysiology of Sickle Cell-Related Kidney Disease Using the SGLT2 Inhibitors, Empagliflozin

Inclusion Criteria: * Documentation of SCA genotype (HbSS or HbSβ0-thalassemia) * Albuminuria defined by a UACR of 100 - 2,000 mg/g creatinine at the screening * Hemoglobin (Hb) ≥ 5.5 g/dL during screening * For participants taking Endari, the dose of Endari must be stable for at least one month prior to signing the ICF and with no anticipated need for dose adjustments during the study * For participants on crizanlizumab or chronic red blood cell transfusions, the therapy must have started at least 3 months prior to consent * For participants taking an angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), the dose must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator * Participants must demonstrate regular compliance with clinic visits and outpatient management * Participants, if female and of childbearing potential, will use highly effective methods of contraception from study start to 30 days after the last dose of the study drug * Participant has provided documented informed consent or assent Exclusion Criteria: * Concurrent diagnosis of diabetes mellitus * Female who is breast feeding, pregnant, or unwilling to use birth control as described in the protocol * Prior hypersensitivity or intolerance to a sodium-glucose cotransporter-2 inhibitor (SGLT2i) * Active or open leg ankle ulcer * Chronic urinary tract infection * Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days prior to signing consent * Hepatic dysfunction characterized by alanine aminotransferase (ALT) \>5× ULN * Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed * Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive * Moderate to severe CKD (defined by an eGFR \< 30 mL/min/1.73m2, on chronic dialysis, or having received a kidney transplantation) * History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy) * History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: 1. Unstable angina pectoris or myocardial infarction or elective coronary intervention 2. Uncontrolled clinically significant arrhythmias * Any condition affecting drug absorption, such as major surgery involving the stomach (e.g. bariatric surgery) or small intestine (prior cholecystectomy is acceptable) * Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of agent, whichever is longer, or is currently participating in another trial of an investigational agent or medical device) * Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent * Contraindication to MRI (certain pacemakers, electronic implants, shrapnel in the eyes, or certain intracranial aneurysm clips)