What dose of lisinopril (angiotensin-converting enzyme inhibitor) should a patient with normal blood pressure and impaired renal function (eGFR of 60) and microalbuminuria start with?

Lisinopril Dosing in CKD Stage 3a with Microalbuminuria and Normal Blood Pressure

This patient should start lisinopril at 2.5 mg once daily, despite having normal blood pressure, because they have microalbuminuria and impaired renal function (eGFR 60 mL/min/1.73 m²), which indicates early diabetic kidney disease requiring RAS blockade for renoprotection. 1, 2

Rationale for Treatment Despite Normal Blood Pressure

• RAS blockers (ACE inhibitors or ARBs) are recommended as part of the treatment strategy in hypertensive patients with microalbuminuria or proteinuria because they are more effective at reducing albuminuria than other antihypertensive agents. 1

• The 2024 ESC Guidelines specifically state that in patients with diabetic or non-diabetic CKD, RAS blockers should be used when microalbuminuria is present, emphasizing their superior effect on reducing albuminuria progression. 1

• While the strongest evidence exists for hypertensive patients, the 2007 KDOQI guidelines suggest that treatment with an ACE inhibitor or ARB may be considered in normotensive people with diabetes and microalbuminuria, though this is a weaker recommendation (Grade C). 1

Starting Dose Selection: 2.5 mg Daily

The FDA-approved dosing for lisinopril requires dose adjustment based on creatinine clearance. 2

• For patients with creatinine clearance ≥10 mL/min and ≤30 mL/min, the initial dose should be reduced to half the usual recommended dose (5 mg for hypertension becomes 2.5 mg). 2

• However, this patient has an eGFR of 60 mL/min/1.73 m², which is above 30 mL/min, so technically no dose adjustment is required per FDA labeling (which states no adjustment needed for creatinine clearance >30 mL/min). 2

• Despite this, starting at 2.5 mg is prudent because:

  • The patient has normal blood pressure (120/80 mmHg), creating risk for hypotension with standard dosing
  • Multiple clinical studies in patients with renal impairment used 2.5 mg as the starting dose for those with GFR <30 mL/min, demonstrating safety and efficacy at this lower dose 3, 4, 5
  • The FDA label recommends 2.5 mg as the starting dose for acute MI patients with low systolic blood pressure (≤120 mmHg), which parallels this clinical scenario 2

Titration Strategy

• Uptitrate as tolerated to a maximum of 40 mg daily to achieve maximal albuminuria reduction, which is the primary treatment target in this patient. 1, 2

• The EUCLID study demonstrated that lisinopril significantly reduced albuminuria progression in normotensive IDDM patients with microalbuminuria, with the greatest effect seen in those with baseline microalbuminuria (49.7% reduction, p=0.001 at 24 months). 6

• Monitor blood pressure closely during titration, as the 2024 ESC Guidelines recommend individualized treatment according to tolerability and impact on renal function and electrolytes in CKD patients. 1

Monitoring Requirements

• Monitor serum creatinine and potassium within 1-2 weeks after initiation and after each dose increase, as ACE inhibitors can cause hyperkalemia and acute changes in renal function. 1, 5

• One study found hyperkalemia occurred in one-third of patients with impaired renal function on lisinopril, necessitating close monitoring. 5

• Assess albuminuria reduction as a treatment target, as treatments that lower urinary albumin excretion may slow progression of diabetic kidney disease and improve clinical outcomes. 1

• The mean GFR remained stable in clinical trials of lisinopril in patients with renal impairment, though individual responses varied. 3, 4, 5

Common Pitfalls to Avoid

• Do not withhold ACE inhibitor therapy solely because blood pressure is normal—the indication here is renoprotection for microalbuminuria, not blood pressure control. 1

• Do not start at 10 mg (the standard hypertension dose) in this patient with normal blood pressure and borderline renal function, as this increases risk of hypotension. 2

• Do not combine ACE inhibitor with ARB, as combination therapy is not recommended due to lack of additive benefit and increased risks for hyperkalemia and acute kidney injury. 1

• Be aware that with prolonged treatment, the dose may need adjustment—one study noted that lisinopril dose could be lowered gradually without losing antihypertensive effect during long-term follow-up. 5