Sickle cell disease: renal manifestations and mechanisms

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.

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Repeated cycles of sickling are thought to cause microinfarctions and renal medullary ischemia [114,115]. Increasing evidence also supports the role of hemolysis and hypoxia-induced oxidative stress in renal injury [116,117]. Despite advances in the pathophysiology of SCD nephropathy, there are no evidence based treatments for children or adults with SCD associated albuminuria, a precursor of significant sickle nephropathy.…”

Acute kidney injury in children with sickle cell disease—compounding a chronic problem

“…These factors ultimately result in impaired blood flow, microinfarctions, and ischemia. Over time, this leads to remodeling of the medullary vasa recta peritubular capillaries with multilayering of the basement membranes, peritubular capillary loss, interstitial fibrosis and tubular atrophy, and papillary necrosis when severe [6][7][8]. The clinical manifestations of renal medullary injury include hyposthenuria, polyuria, metabolic acidosis, and hyperkalemia.…”

“…Hypoperfusion of the medulla results from infarction, thrombosis, and remodeling of the microvasculature, creating a Bperfusion paradox^ [8]. There is a concomitant increase in cortical blood flow that has damaging consequences, such as glomerular hyperfiltration, enlargement of the glomeruli, tubular hypertrophy, and enlarged kidneys.…”

Persistent proteinuria among sickle cell anaemia children in steady state in Ilorin, Nigeria

“…Sickle Cell Foundation, 2016). The cause of the SCD is the substitution of valine for glutamic acid at the sixth position of the β-goblin chain of the haemoglobin (Nath and Hebbel, 2015). The immediate consequence of the mu-tation is that deoxygenated haemoglobin S polymerizes and distorts the shape of the erythrocytes (Manwani and Frenette, 2013).…”