How should chronic kidney disease stage 4 (estimated glomerular filtration rate 15–29 mL/min/1.73 m²) be managed?

Management of CKD Stage 4

Start renin-angiotensin system inhibition with an ACE inhibitor or ARB at the highest tolerated dose (e.g., lisinopril 40 mg daily), add an SGLT2 inhibitor if diabetic with eGFR ≥20 mL/min/1.73 m², target blood pressure <120 mmHg systolic when tolerated, and initiate timely education about kidney replacement therapy options. 1, 2

Patient Education and Preparation for Kidney Failure

• Begin comprehensive education immediately about kidney failure treatment options including kidney transplantation, peritoneal dialysis, home hemodialysis, in-center hemodialysis, and conservative management without dialysis 1
• Include family members and caregivers in these educational discussions 1
• Evaluate benefits, risks, and disadvantages of kidney replacement therapy as patients approach stage 5 CKD (eGFR <15 mL/min/1.73 m²) 1

Renin-Angiotensin System Blockade

Initiation and Dosing

• Start ACE inhibitor or ARB at the highest approved tolerated dose because clinical trials demonstrated blood pressure reduction and renal protection at these target doses in patients with eGFR 15–29 mL/min/1.73 m² 1, 2
• For diabetic patients with moderately-to-severely increased albuminuria (A2 or A3), ACE inhibitor or ARB is strongly recommended 1
• For non-diabetic patients with severely increased albuminuria (A3), ACE inhibitor or ARB is strongly recommended 1
• If ACE inhibitor causes intolerable cough or angioedema, switch to an ARB 2

Monitoring and Continuation

• Check serum creatinine and potassium 2–4 weeks after initiation or dose increase 1, 2
• Continue ACE inhibitor or ARB even when eGFR falls below 30 mL/min/1.73 m² unless specific contraindications develop 1, 2
• A creatinine rise ≤30% within 4 weeks is expected hemodynamic effect and does not require discontinuation 1, 2
• Discontinue only for symptomatic hypotension, refractory hyperkalemia despite medical treatment, or to reduce uremic symptoms when eGFR <15 mL/min/1.73 m² 1, 2

Contraindications

• Never combine ACE inhibitor, ARB, and direct renin inhibitor (triple blockade is contraindicated) 1, 2
• Avoid dual RAS inhibition (ACE inhibitor plus ARB) due to increased risks of hyperkalemia, hypotension, and acute kidney injury 2

Blood Pressure Management

Target Blood Pressure

• Aim for standardized office systolic blood pressure <120 mmHg when tolerated 2
• An alternative target of 130–139 mmHg systolic is acceptable if intensive control is not feasible 2
• Intensive BP targets should only be applied when standardized measurement techniques are used 2

Antihypertensive Regimen

• When blood pressure remains uncontrolled on maximally tolerated ACE inhibitor/ARB, add a loop diuretic (thiazides are ineffective when eGFR <30 mL/min/1.73 m²) 2
• Long-acting dihydropyridine calcium channel blockers (amlodipine, nifedipine) are appropriate as second- or third-line agents 2
• Limit dietary sodium to <2 g/day (≈90 mmol/day) to improve diuretic efficacy and blood pressure control 2

SGLT2 Inhibitor Therapy

For Diabetic Patients

• Treat patients with type 2 diabetes, CKD stage 4, and eGFR ≥20 mL/min/1.73 m² with an SGLT2 inhibitor 1
• Once initiated, continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² unless not tolerated or kidney replacement therapy is initiated 1
• Withhold SGLT2 inhibitor during prolonged fasting, surgery, or critical medical illness when patients may be at greater risk for ketosis 1

For Non-Diabetic Patients

• Treat adults with CKD stage 4 and urine albumin-to-creatinine ratio ≥200 mg/g with an SGLT2 inhibitor 1
• Treat adults with heart failure with an SGLT2 inhibitor irrespective of albuminuria level 1
• Consider SGLT2 inhibitor for adults with urine albumin-to-creatinine ratio <200 mg/g 1

Monitoring

• SGLT2 inhibitor initiation does not necessitate alteration of CKD monitoring frequency 1
• The reversible decrease in eGFR on initiation is generally not an indication to discontinue therapy 1

Nonsteroidal Mineralocorticoid Receptor Antagonist

• Consider nonsteroidal MRA for adults with type 2 diabetes, eGFR >25 mL/min/1.73 m², normal serum potassium, and albuminuria >30 mg/g despite maximum tolerated RAS inhibitor 1
• Most appropriate for adults with type 2 diabetes at high risk of CKD progression and cardiovascular events, demonstrated by persistent albuminuria despite other standard-of-care therapies 1

Hyperkalemia Management

• Treat hyperkalemia with dietary potassium restriction and potassium-binding agents rather than reducing or stopping ACE inhibitor/ARB to preserve renoprotective effects 1, 2
• Hyperkalemia associated with RAS inhibitor use can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping therapy 1

Metabolic Acidosis Management

• Consider base-producing fruits and vegetables or oral sodium bicarbonate for metabolic acidosis with plasma total CO₂ <22 mM 3
• Both approaches improve metabolic acidosis and reduce urine indices of kidney injury without producing hyperkalemia in stage 4 CKD 3

Monitoring and Follow-Up

• Use validated GFR estimating equations to guide decision-making, not simply serum creatinine measurement 1
• Monitor for characteristic complications of kidney failure including malnutrition, fluid overload, bleeding, serositis, depression, cognitive impairment, peripheral neuropathy, and increased infection susceptibility 1

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitor/ARB for modest creatinine rises up to 30%—this reflects hemodynamic effect, not renal injury 2
• Switch from thiazide to loop diuretics when eGFR falls below 30 mL/min/1.73 m² because thiazides are ineffective at this level 2
• Do not use thiazide diuretics as monotherapy in CKD stage 4 2
• Intensive BP targets (<120 mmHg) should only be applied when standardized measurement techniques are used 2