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Review
. 2024;55(1):56-71.
doi: 10.1159/000534865. Epub 2023 Oct 27.

Sickle Cell Disease and CKD: An Update

Rima S Zahr  1 , Santosh L Saraf  2
Affiliations
Review

Sickle Cell Disease and CKD: An Update

Rima S Zahr et al. Am J Nephrol. 2024.

Abstract

Background: Sickle cell disease is an inherited red blood cell disorder that affects approximately 100,000 people in the USA and 25 million people worldwide. Vaso-occlusion and chronic hemolysis lead to dysfunction of vital organ systems, with the kidneys being among the most commonly affected organs.

Summary: Early renal manifestations include medullary ischemia with the loss of urine-concentrating ability and hyperfiltration. This can be followed by progressive damage characterized by persistent albuminuria and a decline in the estimated glomerular filtration rate. The risk of sickle nephropathy is greater in those with the APOL1 G1 and G2 kidney risk variants and variants in HMOX1 and lower in those that coinherit α-thalassemia. Therapies to treat sickle cell disease-related kidney damage focus on sickle cell disease-modifying therapies (e.g., hydroxyurea) or those adopted from the nonsickle cell disease kidney literature (e.g., renin-angiotensin-aldosterone system inhibitors), although data on their clinical efficacy are limited to small studies with short follow-up periods. Kidney transplantation for end-stage kidney disease improves survival compared to hemodialysis but is underutilized in this patient population.

Key messages: Kidney disease is a major contributor to early mortality, and more research is needed to understand the pathophysiology and develop targeted therapies to improve kidney health in sickle cell disease.

Keywords: Albuminuria; Glomerular filtration rate; Kidney disease; Nephropathy; Sickle cell disease.

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Conflict of interest statement

Conflict of Interest Statement: RSZ: No conflicts of interest to declare; SLS: No relevant conflicts of interest related to this manuscript but has served on advisory boards and as a consultant for Global Blood Therapeutics/Pfizer, Novartis, Agios, ORIC, BEAM therapeutics and Forma Therapeutics/Novo Nordisk.

Figures

Figure 1:
Figure 1:
Pathophysiologic mechanisms for kidney damage in sickle cell disease.
Figure 2:
Figure 2:
Overlapping prevalence of the APOL1 G1 and G2 risk variants and the Hemoglobin S mutation in sub-Saharan Africa. Figures adapted with permission from Thomson R, Genovese G, Canon C, et al. Evolution of the primate trypanolytic factor APOL1. Proc Natl Acad Sci USA. 2014; 111(20): E2130-E2139 and from Piel FB, Patil AP, Howes RE et al. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat Commun. 2010; 1:104.
Figure 3:
Figure 3:
Work up for sickle cell-related kidney disease.
See this image and copyright information in PMC

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