Is midodrine (a medication for orthostatic hypotension) contraindicated in patients with Acute Kidney Injury (AKI)?

Midodrine in Acute Kidney Injury

Midodrine is not specifically contraindicated in acute kidney injury (AKI), but should be used with caution in patients with renal impairment, with a reduced starting dose of 2.5 mg recommended. 1

Mechanism and Considerations

Midodrine is an oral alpha-1 adrenergic agonist primarily used for orthostatic hypotension. When considering its use in patients with AKI:

• The FDA label explicitly lists "acute renal disease" as a contraindication for midodrine 1
• However, midodrine is commonly used in hepatorenal syndrome (HRS), a specific form of AKI in cirrhotic patients 2
• The drug requires dose adjustment in renal impairment since desglymidodrine (the active metabolite) is eliminated via the kidneys 1

Use in Hepatorenal Syndrome-AKI

In the context of hepatorenal syndrome-associated AKI (HRS-AKI):

• Midodrine combined with octreotide is widely used in North America for HRS-AKI, particularly where terlipressin is not available 2
• This combination works more slowly than terlipressin but can reverse HRS 2
• Midodrine and octreotide are generally well tolerated, though headaches, blurred vision, cardiac palpitations, and rash may occur with midodrine 2
• The combination is inferior to terlipressin in improving renal function or HRS reversal 2

Dosing Considerations in Renal Impairment

• For patients with renal impairment, the FDA label recommends starting with a reduced dose of 2.5 mg 1
• Renal function should be assessed prior to initial use of midodrine 1
• Higher blood levels would be expected in patients with renal impairment due to reduced elimination 1

Monitoring and Precautions

When using midodrine in patients with AKI, careful monitoring is essential:

• Blood pressure should be monitored carefully, especially when midodrine is used with other vasoconstrictors 1
• Supine hypertension is a significant risk - patients should take their last daily dose 3-4 hours before bedtime 1
• Urinary retention is a potential side effect as desglymidodrine acts on alpha-adrenergic receptors of the bladder neck 1, 3
• Cardiac monitoring may be necessary as midodrine can cause bradycardia, primarily due to vagal reflex 1

Alternative Vasopressors for AKI

In cases where midodrine is contraindicated or insufficient:

• Terlipressin plus albumin is considered the first-line therapy for HRS-AKI 2
• Norepinephrine is an effective alternative to terlipressin but typically requires ICU monitoring 2
• For non-HRS forms of AKI, vasopressors should not be used 2

Clinical Decision Algorithm

1. Assess AKI etiology:

   • If HRS-AKI: Consider vasopressors including midodrine (with octreotide)
   • If non-HRS AKI: Avoid vasopressors including midodrine 2

2. Evaluate renal function:

   • If using midodrine in renal impairment: Start with 2.5 mg dose 1
   • Monitor serum creatinine and urine output

3. Consider alternatives:

   • First choice: Terlipressin plus albumin (if available) 2
   • Second choice: Norepinephrine (if ICU monitoring available) 2
   • Third choice: Midodrine plus octreotide 2

4. Monitor for complications:

   • Blood pressure (risk of supine hypertension)
   • Urinary retention
   • Cardiac effects (bradycardia)

Conclusion

While midodrine is not absolutely contraindicated in all forms of AKI, it should be used with caution, with dose adjustment, and with appropriate monitoring of renal function. The FDA label specifically lists "acute renal disease" as a contraindication, suggesting particular caution is warranted. In the specific context of HRS-AKI, midodrine (with octreotide) represents a third-line therapy after terlipressin and norepinephrine.