Preventing Sickle Cell Kidney Disease
Condition: Anemia, Sickle Cell; Sickle Cell Disease; Kidney Disease; Hypertension; Proteinuria
MeSH terms: Kidney Diseases; Proteinuria; Hypertension; Anemia, Sickle Cell
Intervention: Losartan; Losartan
Intervention description: Standard dosing; Experimental dosing
Intervention MeSH terms: Losartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 5 Years
Maximum age: 25 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Anemia, Sickle Cell; Sickle Cell Disease; Kidney Disease; Hypertension; Proteinuria; Losartan; Antihypertensive Agents; Blood Pressure

Summary:

      Untreated hypertension and renal injury are risk factors for increased morbidity and
      mortality in sickle cell disease, yet early markers of progressive disease have not been
      identified and therapies to prevent the development of adverse cardiovascular outcomes have
      not been defined. Circadian blood pressure, as defined by 24 hour blood pressure monitoring,
      is more accurate than clinic blood pressure in defining secondary hypertension and abnormal
      nocturnal blood pressured dipping and nocturnal hypertension have been linked to progressive
      renal disease in other diseases.

      Methodology/Aims: A randomized feasibility trial of losartan will be conducted among
      adolescent HbSS and SB0 thalassemia patients (11-19 years) with abnormal nocturnal blood
      pressure dipping. During this six month feasibility trial, two dosing strategies of losartan
      (titrated to keep clinic BP <95th percentile vs. <75th percentile) will be analyzed for
      safety and effect on restoring normal circadian blood pressure.

      A prospective cohort study among HbSS and SB0 thalassemia patients (6-19 years) will also be
      conducted to evaluate the incidence of hypertension and role of monitoring potential
      biomarkers of kidney injury and hypertension. Cohort participants will undergo annual
      evaluations of hypertension(24 hour blood pressure monitoring for participants ≥ 11yrs,
      clinic BP in all participants) and markers of kidney injury/hypertension.

      Expected Results: At the completion of the feasibility trial, vital background information
      will be obtained to design a definitive multicenter trial of hypertension in sickle cell
      disease. At the completion of the cohort study, the incidence of pediatric hypertension will
      be identified and the role for monitoring blood and urine biomarkers will be better
      understood.

      As therapy for patients with renal failure is dismal, it is imperative that SCD patients at
      risk are identified early and that therapeutic trials are conducted that prevent progression.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pts with HbSS or SB0 thalassemia

          -  Hypertension from clinic BP readings (defined by NHLBI BP tables)

          -  Abnormal nocturnal dipping (systolic or diastolic) as defined by <10% dip or abnormal
             nocturnal BP load (>25% of sleep BP readings >95th percentile as defined by AHA ABPM
             guidelines)

          -  Signed Informed Consent

        Exclusion Criteria:

          -  Patient already on BP lowering medication

          -  Hyperkalemia

          -  Pregnancy