Sickle Cell Disease
Anthony Chang, MD
Key Facts
Terminology
Sickle cell nephropathy
Etiology/Pathogenesis
β-globin gene mutation
Chromosome 11p15.5
Clinical Issues
Presentation
Chronic kidney disease
Proteinuria
Drugs
Angiotensin-converting enzyme inhibitors
Macroscopic Features
Papillary necrosis
Vascular congestion of vasa recta in renal medulla
Microscopic Pathology
Glomerular hypertrophy
Glomerular sclerosis
Global
Segmental
Duplication of glomerular basement membranes
Hemosiderosis
Ancillary Tests
Electron microscopy
Cytoplasmic rod-like inclusions of polymerized hemoglobin in red blood cells
Top Differential Diagnoses
Focal segmental glomerulosclerosis
Chronic thrombotic microangiopathy
Collapsing glomerulopathy
 Gross photograph shows marked congestion of the vasa recta  in the renal pyramid with prominent scarring of the renal papilla  , as shown by the deep horizontal divot. (Courtesy C. Abrahams, MD.) |
 Periodic acid-Schiff shows segmental sclerosis with accumulation of matrix  and foam cells  and focal prominence of adjacent visceral epithelial cells (or podocytes)  . |
TERMINOLOGY
Synonyms
Sickle cell nephropathy
Definitions
Renal injury due to sickle cell disease
ETIOLOGY/PATHOGENESIS
β-globin Gene Mutation
Chromosome 11p15.5
Single nucleotide change leads to a change in amino acid sequence from glutamic acid to valine
Homozygous mutations
Combinations with various thalassemias may cause less severe renal disease
CLINICAL ISSUES
Epidemiology
Incidence
1 in 500 African American births
Age
3rd to 5th decade
Gender
No gender predilection
Ethnicity
African American predilection
Site
Kidney
Chronic kidney disease in 4-17%
Presentation
Proteinuria (25%)
Nephrotic syndrome (5%)
Hematuria
Often unilateral with left > right kidney involvement
Hyposthenuria
Laboratory Tests
Hemoglobin electrophoresis
Treatment
Surgical approaches
Renal transplantation
Drugs
Hydroxyurea
Angiotensin-converting enzyme inhibitors
Nonsteroidal anti-inflammatory agents
Should be avoided for pain control
May increase risk for papillary necrosis
Hematopoietic cell transplantation
Rare option, possibly curative
Prognosis
Average life expectancy: 48 years
Increased risk of medullary renal carcinoma
More common with sickle cell trait
MACROSCOPIC FEATURES
General Features
Papillary necrosis
15-36% incidence
Vascular congestion of vasa recta in renal medulla
Hypoxic milieu enables sickling of red blood cells
