Please select the eligibility criteria that correspond to the clinical trial below.
Title: Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.
Brief Summary: Patients with sickle cell anaemia may develop renal disease. In fact, renal disease occurred in 40% of adults patients (macroalbuminuria) with evolution to end-stage renal disease for half of them. Microalbuminuria is an early and sensitive marker of glomerular damage. It appears during the first decade and occurred in 20 to 25% of infants (2 to 18 years). Physiopathology of renal scarring is not well understood actually. Renal scarring might be due to glomerular hyperfiltration and vascular and endothelial damage. Angiotensin-converting enzyme inhibitors (ACE) were studied and used in diabetic nephropathy. In a study on 26 sickle cell adults, albuminuria was reduced about 50% by ACE compared to placebo after six months treatment. It might be interesting studying ACE efficacy in sickle cell children with microalbuminuria because renal disease is directly related to sickle cell and is not influenced by other cardiovascular risk factors like in adult patients.

We hypothesized to have a successful ACE treatment in more than 40% of cases after a nine months treatment period. A success is defined as a 50% reduction of the albuminuria/creatinuria ratio.


Options:
A: Inclusion Criteria:

* Sickle cell disease (SS, SC, Sb thalassemia, SD Punjab)
* Affiliation to French Health benefits
* Signed informed consent
* Albuminemia / Creatinemia \>= 3 mg / mmol (on 2 samples)

Exclusion Criteria:

* Albuminemia / Creatinemia \> 100 mg / mmol
* Hypersensibility to enalapril
* Angio-oedemas due to a previous treatment by ACE
* idiopathic or hereditary angio-oedemas
* cerebral echo-doppler
* treatment by lithium digoxine
* treatment by other ACE
* congenital galactosemia
* Pregnancy
B: Inclusion Criteria:

* Homozygous S sickle cell disease
* Diagnosed by newborn screening
* determined to have persistent microalbuminuria
* satisfied criteria for microalbuminuria screening
* parental consent

Exclusion Criteria:

* Asymptomatic bacteriuria on screening urine cultures
* On Hydroxyurea therapy
* Pre-existing complications of SCD which would meet local criteria for HU therapy
C: Inclusion Criteria:

* Patients from birth up to age 30 years
* Diagnosis of sickle cell disease
* Patients who are receiving hydroxyurea therapy or plan to begin hydroxyurea therapy
D: Inclusion Criteria:

* Majority fetal and sickle (FS or SF) hemoglobin pattern confirmed centrally by electrophoresis (screening may begin at 7 months of age)

Exclusion Criteria:

* Chronic transfusion therapy
* Cancer
* Less than 5th percentile (10th percentile for the pilot study) height, weight, or head circumference for age
* Severe developmental delay (e.g., cerebral palsy or other mental retardation, Grade III/IV intraventricular hemorrhage)
* Stroke with neurological deficit
* Surgical splenectomy
* Participating in other clinical intervention trials
* Probable or known diagnosis of Hemoglobin S-Hereditary Persistence of Fetal Hemoglobin
* Known hemoglobin S-beta plus thalassemia (hemoglobin A present)
* Any condition or chronic illness, which in the opinion of the principal investigator, makes participation unadvised or unsafe
* Inability or unwillingness to complete baseline (pre-enrollment) studies, including blood or urine specimen collection, liver-spleen scan, abdominal sonogram, neurological examination, neuropsychological testing, or transcranial Doppler ultrasound (interpretable study not required, but confirmed velocity greater than 200 cm/sec results in ineligibility)
* Previous or current treatment with hydroxyurea (HU) or another anti-sickling drug
* The following exclusion criteria are transient; patients can be re-evaluated for eligibility:

  1. Hemoglobin less than 6.0 gm/dL
  2. Reticulocyte count less than 80,000/cu mm if hemoglobin is less than 9 gm/dL
  3. Neutrophil count less than 2,000/cu mm
  4. Platelet count less than 130,000/cu mm
  5. Blood transfusion in the 2 months prior to study entry unless HbA is less than 10%
  6. ALT greater than twice the upper limit of normal
  7. Ferritin less than 10 ng/ml
  8. Serum creatinine greater than twice the upper limit of normal for age
  9. Bayley standardized mental score below 70

Answer: A