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  • Review Article
  • Published:

Sickle cell disease: renal manifestations and mechanisms

Key Points

  • Sickle cell nephropathy (SCN) largely reflects an underlying renal vasculopathy characterized by the coexistence of cortical hyperperfusion, medullary hypoperfusion, and an increased renal vasoconstrictive response to systemic and regional stress

  • Renal involvement is usually more severe in sickle cell anaemia (HbSS) than in other types of sickle cell disease (HbSC and HbSβ+-thalassaemia), and is typically mildest in sickle cell trait

  • Proteinuria and decreased glomerular filtration rate are independent risk factors for increased mortality in sickle cell disease; 16–18% of overall mortality is estimated to arise from kidney disease

  • The most frequent glomerulopathy in SCD is focal segmental glomerulosclerosis, a lesion considered to be mediated by alterations in glomerular haemodynamics

  • Haematuria and loss of concentrating ability are among the most frequent renal syndromes caused by sickle cell disease, both of which are also common in sickle cell trait

  • Angiotensin-converting-enzyme inhibitor therapy is recommended for patients with SCN and microalbuminuria and proteinuria, even in the presence of normal blood pressure

Abstract

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms.

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Figure 1: The pathobiology of sickle cell disease.
Figure 2: Salient pathogenetic processes in the development of sickle cell nephropathy.

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Acknowledgements

K.A.N. is supported by NIH grants DK47060 and DK70124. We gratefully acknowledge the secretarial expertise of Mrs Kara Sloan in the preparation of this manuscript.

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Correspondence to Karl A. Nath.

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Nath, K., Hebbel, R. Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol 11, 161–171 (2015). https://doi.org/10.1038/nrneph.2015.8

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