Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations.

The underlying mechanisms of disease in sickle cell disease (SCD) contribute to a multi-faceted nephropathy, commonly manifested as albuminuria. In severe SCD genotypes (e.g., HbSS), albuminuria and chronic kidney disease (CKD) are major predictors of mortality in this population. Therefore, the monitoring and management of renal function is an intrinsic part of comprehensive care in SCD. Management of nephropathy in SCD can be accomplished with SCD-directed therapies and/or CKD-directed therapies. In the past 5 years, novel disease-modifying and palliative therapies have been approved in SCD to target aspects of the disease, such as anemia, inflammation and vasculopathy. Along with conventional hydroxyurea and chronic transfusion, L-glutamine, crizanlizumab and voxelotor have all been shown to mitigate some adverse effect of SCD, and their impact on nephropathy is being investigated. CKD-directed therapies such as renin-angiotensin aldosterone (RAAS) system blockers have long been used in SCD nephropathy; however more complete long-term studies on benefits are needed. Given the impact of renal disease on survival, further assessment of the mechanisms and efficacy of these SCD- or CKD-directed therapeutic agents is essential.