Losartan for Sickle Cell Kidney Disease

Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease (SCD)
that begins in childhood and results in renal (kidney) failure and early mortality in nearly
12% of adults with hemoglobin SS (HbSS). The potential for prevention and reversal of kidney
damage in SCD is not known. Albuminuria is a commonly used biomarker of glomerular damage;
however the correlations of albuminuria with specific measurements of glomerular function
and pathophysiology have not been determined. We hypothesize that in patients with
persistent albuminuria despite treatment of SCD with hydroxyurea, losartan will reverse
kidney dysfunction in early stage nephropathy and ameliorate progressive kidney dysfunction
in more advanced nephropathy. The primary aim is to study the acute and longer-term effects
of losartan (study drug) on renal function in children and adults with SCD who have
persistent albuminuria. The renal function tests (research tests) will be done at study
entry (prior to losartan), 1 month, and 1 year after starting losartan therapy. In addition,
subjects are seen each month in clinic and assessed by their regular clinical team. The
second aim is to assess the correlation of changes in albuminuria after 1 month of losartan
with changes in direct measurements of renal function at 12 months, thus determining if the
magnitude of the initial decrease in albuminuria in response to losartan predicts sustained
improvements in renal function.

Losartan is an FDA-approved drug to treat blood pressure to protect the kidneys in people
who have diseases like diabetes and blood pressure. It is not specifically labeled for use
in sickle cell disease.

Thirty subjects, at least 10 years old, will be enrolled from Children's Healthcare of
Atlanta (pediatric subjects) or Grady Memorial Hospital (adult subjects). Subjects are in
the study about 1 year.

Accrual is expected to take 2 years. Study is funded for 3 years.

Inclusion Criteria:

- SCD genotype HbSS or HbS/beta-0-thalassemia

- Age greater than or equal to 10 years old

- Urinary albumin/creatinine ratio (ACR) greater than or equal to 30 mg/gram creatinine
on greater than or equal to 2 occasions separated by one month or more

- current treatment with hydroxyurea and a sustained hematologic response for 6 months
or more prior to enrollment

Exclusion Criteria:

- end-stage renal failure

- known co-existent medical conditions that could affect the kidneys

- chronic therapy with non-steroidal anti-inflammatory drugs

- females who are pregnant

- pre-existing hperkalemia

- current chronic transfusion therapy