What Is a Sickle Cell Disease?
Sickle cell disease affects red blood cells and is a genetic blood disorder. The function of red blood cells is to supply oxygen and hemoglobin from blood to different body parts. Sickle cell anemia affects the red blood cells, turning them into stiff and sticky sickle-shaped discs. As a result, a lack of normal and healthy red blood cells leads to anemia. A baby born with sickle cell anemia can have symptoms like extreme tiredness from anemia, painful and swollen hands and feet, and jaundice. In addition, the spleen may be damaged, affecting immunity and increasing the risk of infections.
The medical condition linked to sickle cell anemia includes vaso-occlusive crises (acute pain crises), acute chest syndrome (clogging of sickle-shaped red blood cells in the blood vessels of the lungs), stroke (altered mental state), splenetic sequestration (enlargement of the spleen due to blocking by sickle cells), bacterial infections like Streptococcus pneumonia, and Haemophilus influenzae, leg ulcers, pulmonary hypertension, and chronic kidney disease.
What Are the Effects of Sickle Cell Anemia on the Kidney?
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Hypertrophy - Hypertrophy is an enlargement of renal and glomerular tissues.
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Altered Hemodynamics - Alterations in renal hemodynamics are caused due to increased renal blood flow rate, plasma flow rate, glomerular filtration rate, and decrease in renal vascular resistance, filtration fraction, and decreased medullary perfusion.
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Hyperfunction of the Proximal Tubule - Increase in the function of the absorption of phosphate, secretion of creatinine and uric acid, and increase in transport of para-aminohippurate characterizes the hyperfunction of the proximal tubule.
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Assorted Glomerulopathies - Glomerular pathologies are caused due to abnormal and excessive deposition of sickle cell red blood cells in the cortical and glomerular capillaries and vasa recta, thickening of the glomerular basement membrane, tubular deposition of iron, interstitial edema, tubulointerstitial inflammation, and fibrosis.
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Chronic Kidney Disease - Chronic kidney disease with proteinuria, either as microalbuminuria (30 to 300 mg per gram creatinine) or macroalbuminuria (more than 300 mg per gram creatinine), can be present.
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Acute Kidney Injury - Acute kidney injury develops during the episodes of painful crises that are complicated by acute multiorgan failure. Haemodialysis is needed during these episodes.
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Impaired Urinary Concentrating Ability - Abnormal deposition of sickle cell RBCs in the vasa recta results in ischemia. It impairs both solute reabsorption by the ascending limb of the loop of Henle and the capacity of the vasa recta to counteract the exchange. This results in a reduction of interstitial osmolality. Reabsorption of water depends on the interstitial osmolality, and hence the concentrating ability is impaired.
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Distal Nephron Dysfunction - Impaired medulla reperfusion is the cause of distal nephron dysfunction. This causes impairment in the ability to secrete potassium and reflects the resistance of the distal nephron to aldosterone. The final result of distal tubule dysfunction is hyperkalemia and hyperchloraemia, resulting in metabolic acidosis.
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Haematuria - The presence of blood in the urine can be life-threatening. It occurs due to the rupture of submucosal capillaries in the renal pelvis or vaso occlusion in the vasa recta.
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Increased Risk of Urinary Tract Infections - Necrosis of the papillary tissues of the kidney can increase the susceptibility to urinary tract infection. In addition, hematuria with flank pain can occur.
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Renal Medullary Carcinoma - Renal medullary carcinoma is a locally invasive, fast-growing malignancy that can occur in the first few decades of sickle cell disease. It can present as hematuria, pain, or a renal mass.
Other symptoms include -
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Fatigue.
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A need to urinate more often.
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Loss of appetite.
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Puffy eyes.
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Dry and itchy skin.
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Trouble with sleep and concentration.
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Nausea or vomiting.
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Darker skin color can be noticed.
How Are Sickle Cell Disease and Its Renal Manifestations Diagnosed?
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Blood Analysis - Different types of hemoglobin in red blood cells can be identified and measured using hemoglobin electrophoresis or high-performance liquid chromatography. Abnormal hemoglobin that causes sickle cell anemia can also be identified using these tests.
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Urine Analysis - A routine test for urine needs to be done to check for the presence of protein (proteinuria) and blood in the urine (hematuria).
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Prenatal Screening - Early diagnosis and treatment of sickle cell anemia before the baby is born can prevent complications and save a life. Prenatal screening is done by taking a sample from the biological mother’s amniotic fluid or placental tissue, and then the samples are examined for signs of the sickle hemoglobin gene that can cause the condition.
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Imaging Techniques - Various imaging techniques like a kidney ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scan can provide essential information about the pathogenesis in the kidney vasculature.
How Are Sickle Cell Disease and Its Renal Manifestations Treated?
The treatment modality includes blood transfusions to treat sickle cell anemia, antibiotics to treat infection, and medications to reduce the symptoms of the complications. These drugs include -
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Hydroxyurea - Hydroxyurea is an anti-cancer drug presently used to treat sickle cell anemia. It is found to be useful in treating acute pain problems, reduction in the need for blood transfusion, rehabilitation in anemia symptoms, and preventing painful swelling.
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L-glutamine Therapy - The drug helps to reduce complications by protecting the sickle cells from being more sickle-shaped.
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Voxelator - This drug prevents the red blood cells with abnormal hemoglobin from converting into sickle cells.
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Crizanlizumab-tcma - This medication is used to reduce the frequency of occurrence of acute pain crises.
In patients with sickle cell disease, angiotensin-converting enzyme inhibitors are prescribed to reduce proteinuria and the progression of chronic kidney disease. Bone marrow or stem cell transplants are the only cure for sickle cell disease, but they are not done very often because of the significant risks involved. Stem cells are the cells produced by the bone marrow that can turn into different types of blood cells. When transplanted from a healthy donor, these stem cells help replace the sickle cells and form normal healthy red blood cells.
Conclusion:
Sickle cell anemia is a genetic disorder. It can pass from parents to the progeny. Prenatal screening can help to identify the fetus with sickle cell anemia and treat it if any of the parents are a carrier of it. Sickle cell anemia with chronic symptoms of kidney disease requires regular monitoring and treatment. Managing the pain and other symptoms using drugs can reduce the severity of the disease.