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Sickle Cell Trait and Renal Disease
Salma M AlDallal 1 and Nasser M AlDallal 2
1. Haematology Laboratory Specialist, Amiri Hospital, Kuwait; 2. General Surgeon, Farwaniya Hospital, Kuwait.
I ndividuals with sickle cell trait (SCT), the heterozygous state of sickle hemoglobin β-globin gene (HbAS), are generally reassured that their
health will not be affected by their carrier status. Renal disease, especially hematuria, is one of the most common and severe complications
experienced by patients with sickle cell disease (SCD); but a complete understanding of the relationship between SCT and the development
of chronic kidney disease (CKD) is still lacking. In this short review, we present an overview of SCT and renal complications in SCT, and discuss and
identify SCT as a risk factor resulting from an interplay between genetic and environmental influences. Although SCT itself may not be a disease
in itself, there is evidence suggesting clinical conditions related to SCT. Additionally, we highlight the rationale for further studies into this area,
which could affect the global public health recommendations on any associated health risks.
Keywords Sickle cell trait, renal failure, chronic kidney disease
Disclosure: Salma M AlDallal and Nasser M AlDallal have
nothing to disclose in relation to this article. No funding
was received in relation to the publication of this article.
Authorship: All named authors meet the International
Committee of Medical Journal Editors (ICMJE) criteria
for authorship of this manuscript, take responsibility
for the integrity of the work as a whole, and have
given final approval to the version to be published.
Open Access: This article is published under the
Creative Commons Attribution Noncommercial License,
which permits any noncommercial use, distribution,
adaptation, and reproduction provided the original
author(s) and source are given appropriate credit.
Received: May 4, 2016
Accepted: July 14, 2016
Sickle cell disease (SCD) is a common and serious inherited hematological disorders in humans.
Globally, the disorder affects approximately 300,000 live births per year, 1 and thus it is among the
most important epidemiological genetic disorders in the world. SCD occurs as a result of substitution
of valine for glutamic acid at the sixth amino acid position of the β-globin gene on the short arm
of chromosome 11; thus, producing an abnormal hemoglobin, called hemoglobin S (HbS), instead of
normal hemoglobin, hemoglobin A (HbA). For the full disorder to be established, this mutation must
be present on both inherited alleles. During deoxygenation, the red blood cells (RBCs) containing HbS
become less deformable and form a “sickle” shape. Therefore, polymerization is governed by local
oxygen tension, and promoted by both acidosis and hyperosmolarity. 2
Sickle cell trait (SCT) is a defined as inheritance of a single copy of the sickle mutation. It is estimated
that the disorder affects one in 12 African Americans and nearly 300 million people worldwide.
Most recently, Naik et al. showed that among African Americans, the presence of SCT was associated
with an increased risk of chronic renal disease (CRD) as compared to normal subjects. 3
Citation: Oncology & Hematology Review, 2016;12(2):95–6
Corresponding Author: Salma M AlDallal,
Haematology Laboratory Specialist; Amiri Hospital, Kuwait.
The complications of SCD are well documented and can affect many organs in the body. Furthermore,
studies reported cases of acute complications in SCT individuals such as splenic infarction, heat
stroke, acute renal failure, and sudden death. 4–7 Renal manifestations are the most frequently reported
complications and include impaired urinary concentration, papillary necrosis, and asymptomatic
hematuria. 7–10 A less common cause of hematuria in these cases is renal medullary carcinoma (RMC),
which is almost exclusively found in patients with sickle hemoglobin β-globin gene (HbAS). 11
Renal complications in sickle cell trait
Regardless of the generally benign nature of SCT, numerous possibly serious complications have
been described over the years. Two rare, but important non-renal complications include increased
risk of splenic infarction provoked by hypoxia after high altitude experience, and increased risk of
sudden death during prolonged physical exercise or training at high altitude. 12 Furthermore, SCT,
alone may not be sufficient for the development of CRD; it could contribute to the progression of
chronic renal failure (CRF) in the presence of additional factors such as diabetes, hypertension,
and autosomal dominant polycystic kidney disease (ADPKD). Furthermore, the pathophysiological
pathways induced by SCT could exacerbate the microvascular complications that arise from
diabetes mellitus since SCT patients and diabetes mellitus are prone to suffering from hematuria
and papillary necrosis. 13,14
Hematuria was first reported in SCT patients more than 50 years ago, 15 and is by far most common
complication of SCT. 12 Data from a large series of African American patients showed that hematuria
accounted for 4% of hospitalization among patients with SCT, about twice the rate among those
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