Hydroxyurea is an antimetabolite which increases the production of HbF and  decreases HbS synthesis leads to a decrease in HbS polymerization. One of the major concerns in using this medication is myelotoxicity and the development of tolerance over time. No significant effect on GFR but has potential benefit on proteinuria, specifically in the pediatric population. The use of hydroxyurea has been shown to decrease lactic hydrogenase and reticulocytes which is typically used as a predictor for CKD progression since it increases during hemolysis. Since a decrease in hemolysis is correlated with positive SCN outcomes, hydroxyurea may be beneficial in decreasing the risk of SCN complications.Erythropoietin stimulating agents (ESAs): During normal kidney function in those with SCD, in response to anemia and hypoxia, erythropoietin synthesis is induced, causing increased erythropoietin compared to baseline. Once GFR falls below 60 mL/min, erythropoietin production also declines and it is recommended to add on an ESA to the current therapy; usually at higher doses. The target hemoglobin level should be lower than a normal patient with CKD because of the risk of vaso-occlusive events. Even in ESRD when those with SCD become transfusion dependent, ESAs can still be used to increase the interval between infusions. If using ESAs, it is important to maintain iron levels to maintain the ability to produce red blood cells especially in those with CKD since sub-clinical bleeding is common, and there is decreased iron absorption.
History
Asfotase alfa was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) in September 2008.Asfotase alfa is manufactured by Alexion Pharmaceuticals and it was granted breakthrough therapy designation by the U.S. FDA in 2015 as it is the first and only treatment for perinatal, infantile and juvenile-onset HPP. It was approved in October 2015, in the U.S. and in August 2015, in the EU.The safety and efficacy of asfotase alfa were established in 99 participants with perinatal (disease occurs in utero and is evident at birth), infantile- or juvenile-onset HPP who received treatment for up to 6.5 years during four prospective, open-label studies. Study results showed that participants with perinatal- and infantile-onset HPP treated with asfotase alfa had improved overall survival and survival without the need for a ventilator (ventilator-free survival). Ninety-seven percent of treated participants were alive at one year of age compared to 42 percent of control participants selected from a natural history study group. Similarly, the ventilator-free survival rate at one year of age was 85 percent for treated participants compared to less than 50 percent for the natural history control participants.Participants with juvenile-onset HPP treated with asfotase alfa showed improvements in growth and bone health compared to control participants selected from a natural history database. All treated participants had improvement in low weight or short stature or maintained normal height and weight.