Sickle Cell Disease and the Kidney: Pathophysiology and Novel Biomarkers

Abstract

Clinical Background: Renal involvement in sickle cell disease (SCD), called sickle cell nephropathy (SCN), includes several renal manifestations, such as renal acidification defect, distal nephron dysfunction, renal papillary necrosis, and proteinuria related to glomerular injury, leading to end-stage renal disease. Epidemiology: Many patients with SCD have a defect in urinary concentration, a problem caused by the destruction of the renal medulla that initiates in childhood. The presence of proteinuria in SCD is age-related and starts as microalbuminuria in adolescence and progresses to macroalbuminuria. Proteinuria is responsible for the progression to chronic kidney disease in some patients with SCD with glomerular filtration rate (GFR) decreased due to interactions between various processes involving the vascular, glomerular, tubular, and interstitial compartments of the kidney. Challenges: Renal complications are hardly identifiable in the early stages, as serum creatinine increases only in the final stages of SCN. Subnormal GFR and elevated serum creatinine levels develop only when there is significant proteinuria. Prevention and Treatment: The identification of biomarkers of early, non-invasive kidney injury, and their inclusion in clinical practice will contribute to the identification of the mechanisms involved in the development of renal syndromes, facilitating the development of more effective strategies in the prevention and treatment of SCD.