Atrasentan in Patients With Proteinuric Glomerular Diseases

Inclusion Criteria:

1. Age 18 years and older for patients in the IgAN, FSGS, and Alport Syndrome cohorts
2. Age 18-70 years for patients in the DKD cohort
3. Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks.

For patients enrolling in IgAN Cohort:

1. Biopsy-proven IgA nephropathy
2. UPCR between 0.5 to less than 1.0 g/g
3. Screening eGFR ≥ 30 mL/min/1.73 m2

For patients enrolling in FSGS Cohort:

1. Biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS
2. UPCR > 1.0 g/g
3. Screening eGFR ≥ 30 mL/min/1.73 m2
4. Subjects receiving systemic corticosteroids or other immunosuppressants must be on a stable dose for at least 12 weeks.
5. BMI ≤ 40 kg/m2

For patients enrolling in Alport syndrome Cohort:

1. Diagnosis of Alport syndrome by genetic testing
2. UPCR > 0.5 g/g
3. Screening eGFR ≥ 30 mL/min/1.73 m2

For patients enrolling in DKD Cohort:

1. Diagnosis of type 2 diabetes mellitus
2. UACR ≥ 0.5 g/g
3. Screening eGFR ≥ 45 mL/min/1.73 m2
4. Receiving a stable dose of SGLT2 inhibitor for at least 12 weeks
5. Willing and able to provide informed consent and comply with all study requirements

Exclusion Criteria:

1. Current diagnosis of another cause of chronic kidney disease or another primary glomerulopathy.
2. History of kidney transplantation or other organ transplantation.
3. Except for FSGS patients, use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months.
4. Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator.
5. History of heart failure or a previous hospital admission for fluid overload.
6. Clinically significant history of liver disease as assessed by the Investigator.
7. Hemoglobin below 9 g/dL as measured by the Investigator or blood transfusion for anemia within the past 3 months.
8. Clinical diagnosis of nephrotic syndrome
9. Malignancy within the past 5 years. Exception to the criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ.
10. For women, pregnant, breastfeeding, or intent to become pregnant during the study.
11. For men, intent to father a child or donate sperm during the study.
12. Recently received an investigational agent.
13. Clinically significant unstable or uncontrolled medical condition as assessed by the Investigator.