Can ramipril (Angiotensin-Converting Enzyme Inhibitor) and furosemide (Loop Diuretic) cause Acute Kidney Injury (AKI) in a frail elderly woman with an episode of vomiting?

Ramipril and Furosemide Can Cause Acute Kidney Injury in Frail Elderly with Vomiting

Yes, the combination of ramipril (an ACE inhibitor) and furosemide (a loop diuretic) can cause acute kidney injury (AKI) in a frail elderly woman experiencing vomiting. This is a high-risk clinical scenario that requires immediate attention.

Pathophysiological Mechanism

The development of AKI in this situation occurs through several mechanisms:

1. Volume Depletion:

   • Vomiting causes fluid loss and volume depletion 1
   • Furosemide further reduces intravascular volume through diuresis 1
   • Elderly patients are particularly susceptible to dehydration due to age-related changes in thirst perception and renal function 2

2. Hemodynamic Effects:

   • Ramipril (ACE inhibitor) causes efferent arteriolar vasodilation in the kidneys 2
   • This reduces glomerular filtration pressure, which normally helps maintain GFR 2
   • In volume-depleted states, this effect is magnified, leading to significant drops in GFR 3

3. Renal Autoregulation Impairment:

   • ACE inhibitors block angiotensin II, which normally helps maintain glomerular filtration during hypotension 2
   • When combined with volume depletion from vomiting and furosemide, this protective mechanism is lost 3

Risk Factors in This Case

Several factors make this patient particularly vulnerable:

• Frailty: Reduced physiological reserve and ability to compensate for hemodynamic changes 2
• Advanced Age: Age-related decline in renal function and autoregulatory capacity 2
• Polypharmacy: The specific combination of an ACE inhibitor with a loop diuretic 4
• Acute Illness: Vomiting causing volume depletion 1

Management Approach

1. Immediate Actions:

   • Temporarily hold both ramipril and furosemide 1
   • Assess volume status and provide appropriate fluid resuscitation 1
   • Monitor renal function, electrolytes, and vital signs 1

2. Laboratory Assessment:

   • Check BUN, creatinine, and electrolytes (particularly potassium) 1
   • Assess acid-base status 2
   • Consider urine microscopy to evaluate for tubular injury 2

3. Medication Adjustments:

   • Only restart medications after volume status is restored and renal function has stabilized 1
   • Consider lower doses or alternative medications based on renal function 3
   • Restart medications sequentially rather than simultaneously 1

Prevention Strategies

For frail elderly patients on this medication combination:

• Educate patients about the importance of maintaining adequate hydration 1
• Provide clear instructions on when to hold medications during acute illness 1
• Consider temporary dose reduction during periods of reduced oral intake 5
• Schedule more frequent monitoring of renal function 1
• Evaluate the need for both medications and consider alternatives when appropriate 2

Evidence Quality and Considerations

The association between this drug combination and AKI is well-established in the literature. A study from the Berlin Case-Control Surveillance Study identified furosemide, ramipril, and other cardiovascular drugs as common causes of drug-induced kidney injury, accounting for 33% of cases 4.

The risk is particularly high in elderly patients. Research shows that the combination of ACE inhibitors with diuretics can lead to functional renal insufficiency, especially in those over 75 years of age 6. In one observational study, patients who developed renal deterioration while on this combination were more likely to be older and taking diuretics 6.

The pharmacokinetics of ramipril are significantly altered in patients with impaired renal function, resulting in higher peak levels and prolonged duration of action 5, which may contribute to the risk of AKI.

While furosemide is commonly used in various stages of AKI, evidence does not support its use to prevent or treat AKI 7. In fact, a Brazilian study found that furosemide use was associated with an increased risk of AKI in critically ill patients (OR = 3.27,95%CI = 1.57-6.80) 8.

It's important to note that transient worsening of kidney function in the setting of ACE inhibitors does not always indicate true tubular injury and may be hemodynamically mediated 2. However, in the context of volume depletion from vomiting in a frail elderly patient, the risk of clinically significant AKI is substantial.