Hydroxyurea and Regression of Sickle Cell Nephropathy: Open Clinical Trial in a Pediatric Population in DR Congo.

Abstract

Background: Renal complications of sickle cell disease are becoming very common, and patients generally do not respond to conventional nephroprotective treatments. Among the drugs used, hydroxyurea (HU) seems to have produced good results according to some studies. This molecule has not yet been evaluated in the DR Congo for this purpose. To evaluate albuminuria and the glomerular filtration rate (GFR) after 9 months of HU treatment in a population of children with incipient sickle cell nephropathy.

Methods: This was an open clinical trial involving sickle cell syndrome children under 18 years of age followed by incipient sickle cell nephropathy (glomerular hyperfiltration =GHF and/or microalbuminuria). A mean HU dose of 20 mg/kg/d was administered to each child, with quarterly clinical and biological controls. GHF (new Schwartz formula) was defined as a rate > 130 ml/min/1.73 m2 for girls and > 140 ml/min/1.73 m2 for boys; albuminuria was defined as the albuminuria/creatinuria ratio (ACR) in mg/g. The Wilcoxon and McNemar tests were used to compare the results at admission and at the 9th month of treatment.

Results: In total, 30 children (mean age 8.9±4.1 years; 40% boys) whose mean fetal hemoglobin (HbF) level increased from 10±7.4 to 18.8±4.9% (p˂0.001), whose mean number of blood transfusions ranged from 7.4±6.7 to 0.1±0.3 bags/month (p˂0.001), and whose number of VOCs ranged from 1.8±1.1 to 0.2±0.4/month (p˂0.03) were included. The frequency of GHF decreased from 30% to 3.3% (p˂0.001). The mean albuminuria decreased from 122.5 ± 16.3 mg/g to 30 ± 2.4 mg/g.

Conclusions: HU improved the course of sickle cell nephropathy. The mechanism of action behind this result appears to be an improvement in blood rheology.