Losartan to Reverse Sickle Nephropathy

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Jessica Harper

Principal Investigator
Alecia Nero, M.D.

Official Title

A Phase II Trial of Losartan to Reverse Sickle Nephropathy

Brief Overview

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.

Participant Eligibility

Inclusion Criteria:

1. Age ≥6 years of age; for no albuminuria (NoA) group age is ≥ 6 years and <21 years of

2. Diagnosis of hemoglobin SS disease or Sβ0 thalassemia by hemoglobin electrophoresis
and/or β-globin gene mapping.

3. Urine osmolality <700 mOsm on first morning urine

4. Written informed consent (and assent, where applicable)

5. Documented urine albumin levels showing either

- NoA:,.UAlb <30mg/g creatinine on a first morning urine

- MiA: UAlb 30-300 mg/g creatinine on a first morning urine or

- MaA: UAlb >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

7. Subjects with child-bearing potential must be willing to use a medically accepted
form of contraception throughout the study.

8. Patients on hydroxyurea 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,

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

10. Hepatic dysfunction defined as ALT or direct bilirubin > 3X upper limit of normal

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