Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease

Eligibility Criteria

• * Adults 18-70 years
• * High Risk APOL1 genotype (i.e., G1G1, G2G2, or G1G2)
• * FSGS diagnosed by kidney biopsy or clinically diagnosed HTN-CKD
• * UACR ≥300 mg/dL
• * Estimated glomerular filtration rate (eGFR) ≥26 ml/min/1.73 m2 at screening
• * Stable antihypertensive regimen for ≥ 1 month prior to enrolment
• * Able to provide written informed consent
• * Diabetes
• * HIV
• * Sickle cell disease.
• * Tip variant of FSGS.
• * Systolic BP \>180 mmHg or diastolic BP \>90 mmHg based on average of 3 measurements.
• * Active serious viral, bacterial, fungal or parasitic infection.
• * Symptomatic herpes zoster infection within 12 weeks prior to study entry.
• * Positive hepatitis B surface antigen during screening (could enroll after treatment).
• * Previous kidney transplant.
• * History of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the ULN or the most recent available total bilirubin ≥1.5 times the ULN
• * Hemoglobin \<10 g/dL.
• * Absolute lymphocyte count (ALC)\<500cells/mm3 or absolute neutrophil count (ANC) \< 1000 cells/mm3.
• * Pregnant or nursing at time of enrollment
• * Prior or current treatment with JAK inhibitor.
• * Current use of potent immunosuppressants such as abatacept, adalimumab, anakinra, azathioprine, certolizumab, etanercept, golimumab, infliximab, probenecid, rituximab, ruxolitinib, sarilumab, tofacitinib, or tocilizumab.
• * High dose corticosteroids (\>10 mg per day of prednisone or equivalent) or an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization.