The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait

ABSTRACT

Introduction: Renal dysfunction is among the most common complication of sickle cell disease (SCD), from hyposthenuria in children to progression to overt chronic kidney disease (CKD) in young adults. Emerging evidence now suggests that sickle hemoglobin-related nephropathy extends to individuals with sickle cell trait (SCT).

Areas covered: This review will highlight the pathophysiology, epidemiology, and management recommendations for sickle hemoglobin-related nephropathy in both SCD and SCT. In addition, it will focus on the major demographic and genetic modifiers of renal disease in sickling hemoglobinopathies.

Expert commentary: Studies have elucidated the course of renal disease in SCD; however, the scope and age of onset of renal dysfunction in SCT has yet to be determined. In SCD, several modifiers of renal disease – such as α-thalassemia, hemoglobin F, APOL1 and HMOX1 – have been described and provide an opportunity for a precision medicine approach to risk stratify patients who may benefit from early intervention. Extrapolating from this literature may also provide insight into the modifiers of renal disease in SCT. Further studies are needed to determine the optimal treatment for sickle hemoglobin-related nephropathy.

KEYWORDS:

• Sickle cell disease
• sickle cell trait
• sickle nephropathy
• hemoglobinopathy
• chronic kidney disease

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

RP Naik is supported in part by National, Heart, Lung, and Blood Institute (NHLBI) [grant K08HL125100].