What are the considerations for using tranexamic acid (TXA) in a patient with Chronic Kidney Disease (CKD) stage 5, also known as End-Stage Renal Disease (ESRD)?

Tranexamic Acid in CKD Stage 5: Dosing and Safety Considerations

Tranexamic acid requires substantial dose reduction (50-70%) in CKD stage 5 patients due to predominant renal elimination and risk of severe neurotoxicity from drug accumulation. 1

Critical Safety Concerns in CKD Stage 5

Neurotoxicity Risk

• Tranexamic acid is 90% renally excreted and accumulates dangerously in severe renal dysfunction, causing seizures and other neurological complications. 1, 2
• Neurotoxicity is the most common manifestation of tranexamic acid toxicity in CKD patients, presenting as seizures, confusion, visual disturbances, and altered mental status. 3
• Risk factors for postoperative seizures include advanced age, underlying neurologic disease, chronic kidney disease, and high tranexamic acid doses. 4
• Four case reports from a single center documented severe neurotoxicity in dialysis patients who received tranexamic acid without dose adjustment—all recovered after drug discontinuation. 3

Thrombotic Complications

• Acute obstructive uropathy from blood clot retention has been reported in kidney transplant recipients taking oral tranexamic acid without dose adjustment. 3
• Ureteric clots and acute renal failure from cortical necrosis represent relative contraindications, though tranexamic acid has been used successfully in selected polycystic kidney disease patients with severe hematuria. 5

Recommended Dosing Adjustments

For CrCl <30 mL/min (CKD Stage 4-5)

• Reduce tranexamic acid dose by 50-70% from standard dosing. 1
• For moderate renal impairment (CrCl 30-60 mL/min), renal clearance is already reduced by 31-44%, necessitating downward dose adjustments. 1

Specific Surgical Context Dosing

• For cardiac surgery in CKD stage 5: Use reduced bolus of 15 mg/kg over 15 minutes followed by maintenance infusion of 5 mg/kg/h for 2 hours (compared to 7.5 mg/kg/h in normal renal function). 6
• For major joint arthroplasty in poor renal function (eGFR <60): Single bolus dosing leads to rapid rise and decline; continuous infusion maintains therapeutic levels of 50-75 mg/L for approximately 4 hours. 6
• Standard cardiac surgery dosing (30 mg/kg loading, 16 mg/kg/h infusion) results in sustained supratherapeutic concentrations for approximately 12 hours in CKD stages 3-5. 7

Monitoring Requirements

Plasma Level Monitoring

• Consider monitoring plasma tranexamic acid levels if available, particularly with prolonged use in severe renal impairment. 1
• Therapeutic plasma concentrations of 50-75 mg/L provide optimal antifibrinolytic effect without excessive accumulation. 6

Renal Function Surveillance

• Monitor for acute deterioration in renal function during prolonged tranexamic acid use in severe renal impairment. 1
• Maintain adequate diuresis during treatment. 1

Clinical Monitoring

• Watch for signs of overdose including gastrointestinal symptoms, orthostatic hypotension, thromboembolic events, and neurological alterations (confusion, visual disturbances, seizures). 1

Clinical Context Considerations

Contraindications in CKD Stage 5

• Subarachnoid hemorrhage is an absolute contraindication due to risk of cerebral edema and infarction. 1
• Recent thrombosis represents a contraindication; relative contraindications include atrial fibrillation and known thrombophilia. 2

Limited Evidence for GI Bleeding

• Tranexamic acid should not be used routinely for acute lower GI bleeding in CKD stage 5 patients—it provides no mortality benefit and increases venous thromboembolism risk. 2
• Exception: For hereditary hemorrhagic telangiectasia with chronic GI bleeding, start at 500 mg twice daily and titrate cautiously, though renal impairment increases neurotoxicity risk. 2

Successful Use Cases

• Tranexamic acid has been used successfully in polycystic kidney disease patients with CKD stage 4 experiencing life-threatening hematuria (1000 mg orally three times daily for one day, then once daily), with hematuria stopping within 24 hours. 5
• This represents an exception where benefits may outweigh risks in carefully selected patients with severe, refractory bleeding. 5

Common Pitfalls to Avoid

• Never use standard dosing without adjustment in CKD stage 5—this is the primary cause of neurotoxicity. 3
• Do not extrapolate trauma or surgical bleeding data to GI bleeding contexts, as mechanisms differ (vascular injury versus fibrinolysis). 2
• Avoid assuming elderly patients (>75 years) have normal renal function—prophylactically adjust doses assuming decreased kidney function. 1
• Do not combine tranexamic acid with antiplatelet therapy in CKD patients, as this substantially elevates bleeding risk. 8

Practical Algorithm for CKD Stage 5

1. Assess absolute contraindications: subarachnoid hemorrhage, recent thrombosis, mechanical heart valves
2. Verify indication: surgical bleeding prophylaxis (cardiac, orthopedic) or life-threatening hematuria in polycystic kidney disease
3. Calculate appropriate dose: reduce by 50-70% from standard dosing based on CrCl
4. Choose delivery method: continuous infusion preferred over bolus dosing to maintain therapeutic levels without peaks
5. Monitor closely: neurological status, bleeding control, renal function, signs of thrombosis
6. Discontinue immediately if neurotoxicity develops—recovery typically occurs without permanent disability 3