Introduction
Anticoagulant-related nephropathy is a condition in which acute kidney injury occurs due to excessive use of anticoagulant medications. It causes acute kidney injury and progressive chronic kidney disease as well. Anticoagulant-related nephropathy indicates renal dysfunction with hematuria. It was initially known as Warfarin-induced nephropathy. Anticoagulant-related nephropathy is associated with increased morbidity and mortality.
What Are Anticoagulant Medications?
Anticoagulant medications are referred to as blood thinners. Anticoagulants are a group of medications that are given to prevent or reduce clot formation in the blood. They are prescribed for patients at a high risk of clot formation. They are given to reduce the chances of developing stroke, deep vein thrombosis, pulmonary embolism, and heart attacks. Anticoagulants interrupt and prevent the process of clot formation. Warfarin and Heparin are commonly used anticoagulants. Warfarin is the mainstay treatment in end-stage renal disease. Heparin is used in nondialysis-dependent chronic kidney disease, but it cannot be used in dialysis patients. Oral anticoagulants like Rivaroxaban, Dabigatran, Apixaban, and Edoxaban are also increasingly used for treating chronic kidney disease.
Why Are Anticoagulant Medications Given for Kidney Diseases?
Individuals with chronic kidney diseases are at high risk for thromboembolic and cardiovascular complications. Anticoagulants are given to reduce the hypercoagulability of blood and to decrease platelet hyperactivity. Chronic kidney disease disrupts the body's homeostasis and results in the activation of the renin-angiotensin-aldosterone system, anemia, uremia, systemic inflammation, changes in mineral metabolism, and platelet hyperactivity.
Chronic kidney disease is prothrombotic in nature and increases the risk of thromboembolic events. It causes hypercoagulability that increases the potential for clot formation and decreases clot breakdown. It is due to the increase in coagulation factors, antifibrinolytic factors, hemoconcentration, and platelet membrane changes, making it proaggregatory. All these pathological variations in chronic kidney disease contribute to thrombosis. Hence, anticoagulants are given to prevent the risk of thrombosis.
What Is Anticoagulant-Related Nephropathy?
The term nephropathy refers to the deterioration of kidney function, which can progress to kidney failure or end-stage kidney disease. Supratherapeutic doses of anticoagulants are the reason for renal dysfunction. Excessive use of anticoagulants causes glomerular hemorrhage. However, overuse of anticoagulants alone is not the reason for nephropathy. Anticoagulants cause nephropathy in the presence of other factors like a decrease in the number of nephrons which causes over-perfusion of the existing glomeruli, and this glomerular hypertension improves the chances for glomerular hemorrhage. An injury to the glomeruli can cause profuse bleeding when high doses of anticoagulants are used.
How Do Anticoagulants Cause Nephropathy?
Anticoagulant nephropathy occurs in individuals receiving anticoagulant therapy with Warfarin or oral anticoagulants like direct thrombin inhibitors or factor Xa inhibitors. Various mechanisms may cause anticoagulant-related nephropathy. The known mechanism involved in anticoagulant nephropathy is glomerular hemorrhage, obstruction of renal tubules by red blood cell casts, and tubular epithelial injury.
Anticoagulants inhibit the activation of vitamin-K-dependent proteins like thrombin and prevent the activation of the proteinase-activated receptor. This destabilizes the capillary endothelium and causes glomerular hemorrhage. Hemorrhage of capillaries and Bowman’s space and obstruction in renal tubules caused by red blood cell casts lead to rupture of the glomerular filtration barrier resulting in injury to the tubular epithelium. The obstruction in the renal tubules caused by red blood cells also causes ischemia. A thin glomerular basement membrane and tubular damage caused by anticoagulants increase the risk of bleeding. Individuals with chronic kidney disease, initial overuse of anticoagulants, cardiovascular diseases, cardiac failure, diabetes, and hypertension are at high risk for developing anticoagulant-related nephropathy. Chronic kidney disease is the major risk factor for developing anticoagulant-related nephropathy.
What Are the Signs and Symptoms of Anticoagulants-Related Nephropathy?
Anticoagulants-related nephropathy is associated with the following signs and symptoms:
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Hematuria (passing blood in urine).
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Passing blood in stools or black stools.
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Swelling of ankles, feet, or hands.
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Muscle cramps.
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Headaches.
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Shortness of breath.
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Increased urination.
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Severe bruising.
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Nose bleeding.
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Vomiting blood.
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Coughing up blood.
What Are the Complications of Anticoagulants-Related Nephropathy?
Anticoagulants cause renal dysfunction. Anticoagulant-related nephropathy may cause irreversible injury and can progress to cause renal failure or end-stage kidney disease. Hematuria is the major complication of anticoagulant-related nephropathy.
What Are the Effects of Anticoagulant-Related Nephropathy?
Anticoagulant-related nephropathy increases the risk of renal morbidity. The obstructive ischemia caused by red blood cells leads to a permanent decrease in the nephron mass of the kidneys. The surviving nephrons undergo hyperfiltration injury due to ischemia. This injury accelerates the progression of chronic kidney disease.
How Is Anticoagulant-Related Nephropathy Diagnosed?
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A major diagnostic criterion for anticoagulant-related nephropathy is renal biopsy. Initial examinations like urinalysis, urine electrolyte analysis, and ultrasound are also performed.
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The histopathological examination showed the presence of diffuse, tubular degenerative, and regenerative changes. It also reveals the presence of dilatation of proximal tubules with flattened epithelia, which is a morphological sign of acute kidney injury. The red cells and red cell casts are present in the lumen of the renal tubules, indicating the presence of tubular injury and hemorrhage. It also shows the presence of bleeding in Bowman’s capsule. The presence of dysmorphic red blood cells in the glomerulus indicates a glomerular filtration barrier.
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Another diagnostic criterion is the increase in serum creatinine level without the presence of other etiologies in the setting of an INR (international normalized ratio) value greater than three.
How Is Anticoagulant-Related Nephropathy Treated?
- The treatment approach for anticoagulant-related nephropathy is the discontinuation of the anticoagulant and using other anticoagulants, using corticosteroids, and reducing the dose of anticoagulants to reduce the INR value to a normal range.
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Corticosteroids are given to improve the course of the treatment. However, the benefits produced by steroids should be weighed against the complications and the risk of infections caused by steroids.
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The INR and renal function are monitored every three to weeks during the initiation of anticoagulant therapy to prevent acute kidney injury.
Conclusion
Anticoagulant medications are used to treat chronic kidney disease. A supratherapeutic dose of anticoagulant causes renal dysfunction in susceptible individuals. It causes acute kidney injury and accelerates the progression of chronic kidney disease. It may progress to cause renal failure and end-stage kidney disease. Hence, it is important to monitor the individuals under anticoagulants to determine renal function. Close monitoring of renal function and timely dose adjustments help prevent anticoagulant-related nephropathy.
