What is the management plan for a patient with chronic kidney disease (CKD), serum creatinine level of 1.0, and elevated Albumin to Creatinine Ratio (ACR), currently on an Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB)?

Management of CKD with Serum Creatinine 1.0 and Elevated ACR on ACE Inhibitor/ARB

Continue Current ACE Inhibitor or ARB Therapy

Continue the ACE inhibitor or ARB at the maximum tolerated dose without discontinuation, as a serum creatinine of 1.0 mg/dL represents normal kidney function and does not warrant any medication adjustment. 1

Monitoring Strategy

Check serum creatinine and potassium within 2-4 weeks of any dose adjustment, then monitor based on CKD stage and albuminuria level. 1

• For patients with elevated ACR (≥30 mg/g), monitor albuminuria and eGFR at least annually to assess treatment response and disease progression 1
• Monitor serum potassium periodically when using ACE inhibitors or ARBs, particularly if eGFR falls below 60 mL/min/1.73 m² 1
• An initial reduction of >30% in albuminuria sustained over at least 2 years indicates effective renal protection 1

Add SGLT2 Inhibitor Therapy

For patients with type 2 diabetes, CKD, and elevated ACR, add an SGLT2 inhibitor immediately if eGFR ≥20 mL/min/1.73 m² to reduce CKD progression and cardiovascular events. 1

• SGLT2 inhibitors provide kidney protection independent of glucose control through multiple mechanisms including reducing intraglomerular pressure, oxidative stress, and inflammation 1
• Continue SGLT2 inhibitor even if eGFR subsequently falls below 20 mL/min/1.73 m² unless not tolerated or kidney replacement therapy is initiated 1
• The reversible decrease in eGFR upon SGLT2 inhibitor initiation does not necessitate discontinuation 1

Consider Nonsteroidal Mineralocorticoid Receptor Antagonist

If eGFR ≥25 mL/min/1.73 m² and albuminuria persists despite ACE inhibitor/ARB and SGLT2 inhibitor therapy, add a nonsteroidal MRA (finerenone) to further reduce cardiovascular events and CKD progression. 1

• Nonsteroidal MRAs do not increase AKI risk when used to slow kidney disease progression 1
• Monitor potassium levels carefully when adding MRA therapy 1

Optimize ACE Inhibitor/ARB Dosing

Titrate the ACE inhibitor or ARB to the maximum tolerated dose used in clinical trials, as low doses provide no benefit. 1

• All clinical trials demonstrating efficacy in slowing kidney disease progression used maximally tolerated doses, not low doses 1
• Do not reduce or discontinue ACE inhibitor/ARB for creatinine increases up to 30% from baseline in the absence of volume depletion 1
• Small elevations in serum creatinine (up to 30%) with RAS blockers should not be confused with acute kidney injury 1

Critical Pitfall to Avoid

The most common error is underdosing or discontinuing ACE inhibitors/ARBs due to fear of creatinine elevation. 1

• An early rise in serum creatinine of approximately 25% above baseline after initiating ACE inhibitor/ARB therapy is expected and associated with long-term preservation of renal function 2, 3
• This rise typically occurs during the first 2-4 weeks and stabilizes thereafter with normal salt and fluid intake 2
• Patients with baseline renal insufficiency who show this early creatinine rise have 55-75% lower risk of worsening renal function compared to those with normal renal function 2

Blood Pressure Management

Target blood pressure <130/80 mmHg for patients with albuminuria ≥30 mg/g creatinine. 1, 4

• For patients with albuminuria <30 mg/g, target blood pressure ≤140/90 mmHg 1
• ACE inhibitors or ARBs should be first-line therapy for hypertension when albuminuria is present 1
• Additional agents (dihydropyridine calcium channel blockers or diuretics) are often needed to achieve blood pressure targets 1

Avoid Combination RAS Blockade

Never combine ACE inhibitor with ARB or direct renin inhibitor, as this increases adverse events without additional benefit. 1

• Combination therapy increases hyperkalemia and acute kidney injury rates 1
• Two clinical trials found no benefits on cardiovascular or kidney outcomes with combination therapy 1

When to Discontinue ACE Inhibitor/ARB

Discontinue or reduce ACE inhibitor/ARB only if: 1

• Serum creatinine rises >30% within 4 weeks of initiation or dose increase 1
• Symptomatic hypotension occurs 1
• Uncontrolled hyperkalemia persists despite medical treatment 1
• Volume depletion is present 1

Hyperkalemia Management

If hyperkalemia develops, manage with measures to reduce serum potassium rather than discontinuing the ACE inhibitor/ARB. 1

• Initiate or adjust diuretic therapy 5
• Use sodium bicarbonate if metabolic acidosis is present 5
• Consider gastrointestinal cation exchangers for persistent hyperkalemia 5
• Concomitant diuretic use reduces hyperkalemia risk by approximately 60% 2

Additional Cardiovascular Risk Reduction

Consider adding a GLP-1 receptor agonist if cardiovascular risk is predominant, as these agents reduce cardiovascular events and slow CKD progression. 1, 4

• GLP-1 RAs have direct renal effects independent of glucose control 1
• Semaglutide can be used as a first-line agent for people with CKD 1

Nephrology Referral Criteria

Refer to nephrology if: 1

• eGFR <30 mL/min/1.73 m² 1
• Continuously increasing urinary albumin levels despite treatment 1
• Continuously decreasing eGFR 1
• Uncertainty about the etiology of CKD 1
• Difficult management issues 4