Inclusion Criteria:

• Age 40-80 years old.
• Chronic kidney disease estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73m^2.
• For the diabetic kidney disease (DKD) subgroup: Diabetes mellitus (on medication).

Exclusion Criteria:

• Hemoglobin A1c > 11% at screening for the DKD subgroup.
• Body weight > 150 kg or body mass index > 50.
• Pregnancy.
• Active glomerulonephritis treated with immunosuppressive therapy.
• Solid organ transplantation (e.g., kidney, pancreas, liver, lung, heart).
• Active immunosuppression therapy.
• History of active substance abuse (including alcohol) within the past 2 years.
• Current alcohol abuse (> 3 alcoholic beverages/day or > 21 per week).
• Human immunodeficiency virus infection.
• Active hepatitis B or C infection.
• Total bilirubin > 2x upper limit of normal.
• Uncontrolled psychiatric disorder.
• Uncontrolled systemic lupus erythematosus.
• Uncontrolled pleural/pericardial effusions or ascites.
• New invasive cancer except non-melanoma skin cancers.
• Invasive fungal or viral infection.
• Inability to tolerate oral medications.
• Known hypersensitivity or allergy to Fisetin.
• Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6CYP2C9, CYP2C19, CYP1A2, Other (OATP1B1) (Unless willing and able to stop or modify the dosing of the drug)  or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus). 
• Tyrosine kinase inhibitor therapy.
• Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc.).
• Subjects on full-dose 325 mg aspirin or other anti-platelet agents (e.g., clopidogrel) daily who are unable or unwilling to reduce or hold therapy prior to and during the 2-day drug dosing. Subjects may continue their previous regimen on day 3.
• Baby aspirin (81 mg), if necessary for cardioprotection, will be allowed but encouraged to hold.
• Subjects taking proton pump inhibitors who are unable or unwilling to reduce or hold therapy 2 days prior to and during the 2-day drug dosing. Subjects taking H2-antagonists and unwilling to discontinue therapy for 2 weeks before and one week following enrollment.
• Subjects taking glimepiride or glyburide for diabetes therapy who are unable or unwilling to reduce or hold therapy prior to and during the 2-day drug dosing.
• Subjects taking the following antimicrobial agents:  Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin, erythromycin), Antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir), Rifampin.
• Tobacco use (smoking or chewing; Unless subject willing to reduce use by 50% prior to and during the study) – see Behavioral Modification information below.
• Inability to give informed consent.
• Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial.

• *Active immunosuppression therapy may include common systemic drugs such as tacrolimus, sirolimus, cyclosporin, cyclophosphamide, rituximab (or other monoclonal antibodies), or mycophenolate mofetil. Most potential subjects on these medication therapies will be identified through the exclusion criteria outlined above.

Behavioral Modification - Participants will be educated about the risk of tobacco and excessive caffeine usage.  Participants will be encouraged to reduce use by 50% prior to and during the 2-day drug dosing period.  Due to drug-drug interaction, subjects may not clear the nicotine (or caffeine) from their system properly/as usual.