Zibotentan and Dapagliflozin for the Treatment of CKD (ZENITH-CKD Trial)

Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: * Diagnosis of Chronic kidney disease (CKD), defined as: (a) eGFR chronic kidney disease epidemiology collaboration (CKD-EPI) ≥ 20 mL/min/1.73 m\^2, and (b) UACR ≥ 150 and ≤ 5000 mg albumin/g creatinine, based on a single first morning void spot urine sample at screening. * No current or prior (within 1 month of screening) medical treatment with an SGLT2i (sodium-glucose co-transporter 2 inhibitor) or any fixed dose combination with SGLT2i. * If Angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin receptor blockers (ARB) and/or mineralocorticoid receptor agonist are prescribed, the dose must be stable ≥ 4 weeks before screening. Participants who have been deemed unable to tolerate ACEi or ARB therapy due to allergy or complications can be enrolled. * No current or prior treatment within 6 months prior to screening with cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary kidney disease. * Body mass index ≤ 40 kg/m\^2. * Male or female of non-childbearing potential. * Female participants must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria: * Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range. * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation. * Male participants must be surgically sterile, abstinent, or in conjunction with a female sexual partner, using a highly effective method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of investigational product to prevent any pregnancies. Male study participants must not donate or bank sperm during this same time period. * Capable of giving signed informed consent, as described in Appendix A, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses. * Provision of signed and dated written Genetic informed consent prior to collection of samples (optional) for genetic analysis. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * Minimal change disease, unstable rapidly progressing renal disease, and/or renal disease requiring significant immunosuppression, autosomal dominant or autosomal recessive polycystic kidney disease. * Participants with New York Heart Association classification functional heart failure (HF) class III or IV. * Acute coronary syndrome events within 3 months prior to screening. * Participants with a B-type natriuretic peptide (BNP) ≥ 200 pg/mL or NT-proBNP ≥ 600 pg/mL (BNP ≥ 400 pg/mL or NT-proBNP ≥ 1200 pg/mL, respectively, if associated with atrial fibrillation) measured by local laboratory at screening (Visit 1). * Participants with unstable HF requiring hospitalisation for optimisation of HF treatment and/or who have not been stable on HF therapy within 6 months prior to screening * Heart failure due to cardiomyopathies that would primarily require other specific treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditions (ie, chemotherapy, infective myocarditis, septic cardiomyopathy). * High output HF (eg, due to hyperthyroidism or Paget's disease). * Heart failure due to primary cardiac valvular disease/ dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement. * Participants with uncontrolled diabetes mellitus (HbA1c \> 12%). * Participants with Type 1 diabetes mellitus. * Hyponatremia, defined as serum Na+ \< 135 mmol/L at the time of screening (Visit 1). * Intermittent or persistent second or third degree atrioventricular block after sinus node dysfunction, with clinically significant bradycardia or sinus pause when not treated with pacemaker. * Prolonged QT interval (QTcF \> 470 ms) on ECG at screening (Visit 1) or randomisation visit (Visit 2), known congenital long QT syndrome or history of QT prolongation associated with other medications. * History of any life-threatening cardiac dysrhythmia (continuous or paroxysmal or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter). * Cardiac surgery or non-elective percutaneous coronary interventions (PCI/TAVI) (within 3 months) or open chest coronary artery bypass grafting or valvular repair/replacement (within 3 months) prior to screening or is planned to undergo any of these procedures after randomisation. * Heart transplantation or left ventricular assist device at any time. * Kidney or any organ transplantation. * History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i (eg, dapagliflozin, canagliflozin, empagliflozin) or drugs with a similar chemical structure to zibotentan. * Any clinically significant disease or disorder (eg, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, major physical impairment), which might put the participant at risk because of participation in the study, or probable alternative primary reason for participant's symptoms in judgment of investigator, including but not limited to: * Isolated pulmonary arterial hypertension \[PAP\] (defined as mean PAP ≥ 25 mmHg at rest) or right ventricular failure; in the absence of left-sided HF * Anaemia defined as haemoglobin (Hb) level \< 100 g/L or 10 g/dL at screening (Visit 1) * Severe chronic obstructive pulmonary disease or other lung disease including but not limited to pulmonary fibrosis requiring chronic oxygen therapy, regular nebuliser use, or oral steroid therapy * Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to screening. * Severe hepatic impairment (Child-Pugh class C Hepatic impairment), aspartate transaminase or alanine transaminase \> 2x the upper limit of normal \[ULN\]; or total bilirubin \> 2x ULN at time of screening. * Participants with newly detected pathological laboratory values or an ongoing disease condition requiring investigation and/or initiation or adjustment of current treatment (in the opinion of the investigator). * Positive hepatitis C antibody, or hepatitis B virus, surface antigen at screening. * Positive human immunodeficiency virus (HIV) test. * Participants treated with strong or moderate CYP3A4 inhibitor or inducer. * Any condition outside the renal and CV disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator's clinical judgment. * Confirmation of corona virus disease- 2019 (COVID-19) infection: * Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 during screening. Participants who are not hospitalised for COVID-19 infections can be re screened 4 weeks after they have recovered. * Participant has been previously hospitalised with COVID-19 infection. * Ejection fraction \< 50% measured by echocardiogram at screening. * Participation in another clinical study with an investigational product administered in the last 3 months prior to screening. * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). * Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. * Previous randomisation into the present study. * Plasma donation within 1 month of the visit at the clinic or any blood donation/blood loss \> 500 mL during the 3 months prior to any visit at the clinic. * Male participant in a sexually active relation with pregnant or breastfeeding partner. * Participants can decline to participate in the genetic research and may still participate in the study. Exclusion from this optional genetic research may be for any of the exclusion criteria specified for the main study or any of the following: * Previous allogeneic bone marrow transplant. * Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.