What is the role of Angiotensin-Converting Enzyme inhibitors (ACE-i) in managing chronic kidney disease (CKD)?

Role of ACE Inhibitors in Chronic Kidney Disease

ACE inhibitors are strongly recommended as first-line therapy for patients with chronic kidney disease (CKD), particularly those with albuminuria, as they slow disease progression and reduce mortality by decreasing glomerular pressure and proteinuria beyond their blood pressure-lowering effects.

Mechanism of Action and Benefits

• ACE inhibitors work by inhibiting angiotensin-converting enzyme, reducing angiotensin II formation, which leads to predominant efferent arteriolar vasodilation and decreased glomerular capillary pressure 1, 2
• This hemodynamic effect results in initial reduction of glomerular filtration rate (GFR) but provides long-term renoprotection by reducing hyperfiltration injury 1, 3
• ACE inhibitors effectively reduce proteinuria/albuminuria, which is a strong predictor of CKD progression and cardiovascular outcomes 1, 4
• They slow progression to end-stage renal disease (ESRD) more effectively than other antihypertensive classes in both diabetic and non-diabetic kidney disease 1

Specific Indications by Patient Population

Diabetic Kidney Disease

• For patients with type 1 diabetes and macroalbuminuria: ACE inhibitors are strongly recommended as they reduce albuminuria and slow GFR decline 1
• For patients with type 2 diabetes and macroalbuminuria: Both ACE inhibitors and ARBs are effective in slowing kidney disease progression 1
• For patients with diabetes, hypertension, and albuminuria: ACE inhibitors should be titrated to the highest tolerated dose 1

Non-Diabetic Kidney Disease

• For non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours: ACE inhibitors are recommended to reduce proteinuria and slow progression 1
• For patients with CKD without albuminuria: Blood pressure control to ≤140/90 mmHg is recommended, with ACE inhibitors being a reasonable option 1

Blood Pressure Targets

• For CKD patients with urine albumin excretion <30 mg/24 hours: Target BP ≤140/90 mmHg 1
• For CKD patients with urine albumin excretion ≥30 mg/24 hours: Target BP ≤130/80 mmHg 1

Monitoring and Management

• Monitor serum creatinine and potassium within 1-2 weeks after initiation or dose adjustment 1
• An initial increase in serum creatinine of 10-20% is expected and not a reason to discontinue therapy 1, 3
• Consider discontinuation if serum creatinine increases by >30% from baseline 1
• Temporarily suspend ACE inhibitors during:
  • Acute illness with volume depletion (diarrhea, vomiting) 1
  • Planned IV radiocontrast administration 1
  • Major surgery 1

Precautions and Contraindications

• Use caution in patients at risk for acute kidney injury: severe heart failure, volume depletion, or concomitant NSAID use 1
• Avoid combining ACE inhibitors with ARBs due to increased risk of adverse effects without additional benefit 1
• Monitor for hyperkalemia, especially in patients with reduced GFR 1, 2
• Consider starting at lower doses in patients with GFR <45 ml/min/1.73m² 1

Special Considerations

• In advanced CKD (eGFR <30 ml/min/1.73m²), recent evidence suggests continuing ACE inhibitors may still be beneficial, contrary to previous concerns 5
• For elderly patients with CKD, gradually escalate treatment with close attention to adverse events 1
• In patients with sickle cell disease and albuminuria, ACE inhibitors or ARBs may reduce albuminuria but require careful monitoring 1

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitors solely due to an initial modest increase in serum creatinine (up to 30%), as this indicates the drug is exerting its desired hemodynamic effect 1, 3
• Do not withhold ACE inhibitors from patients with heart failure, diabetes, or chronic renal failure due to fear of adverse effects, as these patients often derive the greatest benefit 3, 6
• Do not combine ACE inhibitors with ARBs as this increases adverse effects without improving outcomes 1
• Do not forget to adjust dosing in patients with reduced renal function (except for fosinopril which has dual elimination) 7

ACE inhibitors remain cornerstone therapy in CKD management, with substantial evidence supporting their use to reduce proteinuria and slow disease progression across various patient populations with kidney disease.