Losartan to Reverse Sickle Nephropathy

Sickle cell disease causes kidney damage with increasing age, leading to chronic kidney disease and renal failure in nearly one third of patients with sickle cell disease. Currently, there is no treatment for sickle cell related kidney disease.

The purpose of this research study is to see if losartan can help reduce or reverse damage done to the kidneys of children and adults with Sickle Cell Anemia (SCA) and Sickle Beta-zero (HbSβ0) Thalassemia.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥6 years of age; for no albuminuria (NoA) group age is ≥ 6 years and \<21 years of age
2. Diagnosis of hemoglobin SS disease or Sβ0 thalassemia by hemoglobin electrophoresis and/or β-globin gene mapping.
3. Urine osmolality \<700 mOsm (milliosmoles) on first morning urine
4. Written informed consent (and assent, where applicable)
5. Documented urine albumin to creatinine ratio (UACR) showing either

   * NoA: UACR \<30mg/g creatinine on a first morning urine
   * MiA: UACR 30-300 mg/g creatinine on a first morning urine or
   * MaA: UACR \>300 mg/g creatinine on a first morning urine sample
6. A documented negative serum pregnancy test for females with child bearing potential or greater than 10 years of age within (prior to) 7 days of starting the study medication.
7. Subjects with child-bearing potential must be willing to use a medically accepted form of contraception throughout the study.
8. Patients on hydroxyurea (HU) who are on a stable (not changing) dose of HU for three months prior to study entry.

Exclusion Criteria:

1. Patients with Hb SC, SD, Sβ+thal, SE and other sickle hemoglobinopathies, and sickle trait (AS).
2. Pregnant or lactating females, or females of child-bearing potential that are unable to use a medically accepted form of contraception throughout the study.
3. Urine creatinine clearance (Clcr) \<60 mL/minute/1.73 m2
4. Gross (not microscopic) hematuria. If hematuria has resolved for 2 weeks or more, patients will be eligible.
5. Hyperkalemia (K≥5.5) at baseline despite a low potassium diet
6. Concurrent condition that predisposes to nephropathy, such as lupus, diabetes, and hypertension, not controlled with medications..
7. On a renin-angiotensin pathway inhibitor (e.g., captopril, lisinopril, Losartan, valsartan, etc) for the last two weeks prior to enrollment.
8. Hypersensitivity to Angiotensin II receptor blockers such as losartan, valsartan, telmisartan.
9. Patients on red cell apheresis or ongoing aggressive chronic transfusions (one or more a month with a goal of HbS \< 30%). Patients receiving a simple transfusion for symptoms during acute event will be eligible, but if they receive a partial or full exchange transfusion during an acute event, then they will only be eligible after 90 days.
10. Hepatic dysfunction defined as ALT (alanine aminotransferase) or direct bilirubin \> 3-times upper limit of normal (ULN).
11. Chronic therapy with NSAIDS or Cox2 inhibitors
12. On another interventional trial. May be eligible two weeks after completion of another interventional study.
13. Any condition that interferes with the ability of the patient to understand or comply with the treatment plan and follow up.
14. A serious mental or physical illness or a major disease (cardiac, renal, hepatic, neurological, endocrine, metabolic, pulmonary function or psychiatric), which in the opinion of the investigator would compromise participation in the study.
15. Unable to take oral medications.
16. HIV confirmed positive.
17. Chronic therapy with steroids. May be eligible after three weeks of completing steroid therapy.
18. Patients on lithium will be excluded