Losartan to Reverse Sickle Nephropathy
Condition: Nephropathy; Sickle Cell Anemia
MeSH terms: Kidney Diseases; Anemia, Sickle Cell
Intervention: Losartan
Intervention description: Form: suspension, tablet. Dosage & frequency: age 6-16 = 0.7mg/kg once daily; age >16 = 50mg once daily. Duration: 6 months
Intervention MeSH terms: Losartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No

Summary:

      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.
    

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