Do Angiotensin-Converting Enzyme (ACE) inhibitors have any effect on patients with chronic kidney disease or those undergoing dialysis?

Effects of ACE Inhibitors in Chronic Kidney Disease and Dialysis

ACE inhibitors are strongly recommended for patients with chronic kidney disease with albuminuria, as they slow disease progression and reduce mortality, but should be used cautiously in dialysis patients due to potential risks of hyperkalemia and hypotension.

Benefits of ACE Inhibitors in CKD

Renoprotective Effects

• ACE inhibitors provide significant renoprotection in CKD patients, particularly those with:
  • Type 1 diabetes with macroalbuminuria (strong evidence) 1
  • Type 2 diabetes with macroalbuminuria (strong evidence) 1
  • Non-diabetic kidney disease with proteinuria >1g/day 1

Mechanism of Action

• ACE inhibitors provide kidney protection through multiple mechanisms:
  • Reduction of systemic blood pressure
  • Reduction of intraglomerular pressure via efferent arteriolar dilation
  • Antiproliferative effects
  • Reduction of proteinuria
  • Lipid-lowering effects in proteinuric patients 2

Evidence of Benefit

• In type 1 diabetes with macroalbuminuria: The Captopril Study Group trial demonstrated that captopril effectively reduced albuminuria and slowed GFR decline and onset of kidney failure 1
• In type 2 diabetes with macroalbuminuria: The IDNT and RENAAL trials showed ARBs (similar mechanism to ACE inhibitors) slowed GFR decline and reduced progression to kidney failure 1
• Meta-analysis data shows ACE inhibitors reduce the risk of doubling serum creatinine or developing ESRD by 40% (RR 0.60,95% CI 0.49-0.73) 3

Considerations for Specific CKD Populations

Microalbuminuria

• ACE inhibitors reduce progression from microalbuminuria to macroalbuminuria by 65% (RR 0.35,95% CI 0.24-0.53) 3
• Recommended for patients with diabetes and microalbuminuria despite moderate evidence 1

Macroalbuminuria

• Strong recommendation for ACE inhibitors in patients with macroalbuminuria, especially in:
  • Type 1 diabetes (strong evidence) 1
  • Type 2 diabetes (strong evidence) 1

Blood Pressure Targets

• Optimal systolic blood pressure range: 110-129 mmHg
• Patients with proteinuria >1g/day benefit most from this target range 4
• Systolic BP <110 mmHg may actually increase risk of kidney disease progression 4

Cautions and Monitoring

Risk of Acute Kidney Injury

• ACE inhibitors can cause acute kidney injury in specific situations:
  • Bilateral renal artery stenosis or stenosis in a solitary kidney
  • Severe volume depletion
  • Concomitant use of NSAIDs or other nephrotoxic medications 1, 5
  • MAP <65 mmHg 1

Monitoring Requirements

• Check serum creatinine and potassium within 7 days of starting therapy 5
• A rise in serum creatinine up to 30% without hyperkalemia is acceptable and does not warrant discontinuation 1, 5
• Monitor creatinine and eGFR every 3-6 months based on CKD stage 5
• Regularly monitor potassium levels, especially when using ACE inhibitors 5

Medication Interactions

• Avoid the "triple whammy" effect: ACE inhibitors + NSAIDs + diuretics significantly increases AKI risk 5
• Avoid dual RAS blockade (ACE inhibitor + ARB) due to increased risk of hyperkalemia and acute kidney injury 5
• Adjust doses of renally cleared medications according to current eGFR 5

ACE Inhibitors in Dialysis Patients

Benefits

• May help control blood pressure
• May provide cardiovascular protection

Risks

• Increased risk of hypotension during dialysis, particularly with polyacrylonitrile dialysis membranes 1
• Higher risk of hyperkalemia
• Potential for anaphylactoid reactions with certain dialysis membranes 1

Dosing Considerations

• Dose reduction necessary for most ACE inhibitors in renal insufficiency (exception: fosinopril) 2
• Consider ACE inhibitors with hepatic clearance rather than solely renal clearance 1
• When selecting an ACE inhibitor for dialysis patients, choose one that is not significantly dialyzed for stable therapy 1

Practical Recommendations

1. For CKD patients with albuminuria:

   • Start with low dose ACE inhibitor ("start low - go slow") 2
   • Target maximum tolerated dose as used in clinical trials 1
   • Monitor for creatinine increase (acceptable up to 30% if stable) 1
   • Check potassium levels regularly

2. For dialysis patients:

   • Use with caution
   • Select appropriate ACE inhibitor based on clearance mechanism
   • Monitor blood pressure closely, especially during dialysis
   • Be vigilant for hyperkalemia

3. When to avoid or discontinue:

   • Bilateral renal artery stenosis
   • Severe hyperkalemia (>5.5 mEq/L)
   • Acute kidney injury not explained by other causes
   • Symptomatic hypotension

ACE inhibitors remain a cornerstone therapy for CKD patients with albuminuria, with strong evidence supporting their use to slow disease progression and improve outcomes. However, their use in dialysis patients requires careful consideration of risks and benefits on an individual basis.