What is the gold‑standard prescription for an adult with chronic kidney disease?

Gold Standard Prescription for Chronic Kidney Disease

The gold standard prescription for adults with chronic kidney disease consists of SGLT-2 inhibitors combined with renin-angiotensin system inhibitors (ACE inhibitors or ARBs), with risk-stratified addition of nonsteroidal mineralocorticoid receptor antagonists for high-risk patients. 1

Core Foundational Therapy (All CKD Patients)

SGLT-2 Inhibitors - First-Line Therapy

SGLT-2 inhibitors are now the cornerstone of CKD management and should be prescribed for all adults with CKD and eGFR ≥20 ml/min/1.73 m², regardless of diabetes status. 1

• Strong recommendation (1A) for patients at high or very high risk of CKD progression (those with eGFR ≥20 ml/min/1.73 m² with urine albumin-to-creatinine ratio ≥200 mg/g, or concurrent heart failure at any albuminuria level) 1
• Weak recommendation (2B) for patients with eGFR 20-45 ml/min/1.73 m² and urine ACR <200 mg/g 1
• Continue SGLT-2 inhibitors even if eGFR falls below 20 ml/min/1.73 m² after initiation, unless not tolerated or kidney replacement therapy is started 1, 2
• Temporarily withhold during prolonged fasting, surgery, or critical illness due to ketosis risk 1, 2

Renin-Angiotensin System Inhibitors (ACE-I or ARB)

ACE inhibitors or ARBs form the second pillar of CKD therapy and should be prescribed at maximum tolerated doses. 1, 2

• Strong recommendation (1B) for patients with severely increased albuminuria (A3) without diabetes 1
• Strong recommendation (1B) for patients with moderately-to-severely increased albuminuria (A2 and A3) with diabetes 1
• Use the highest approved dose tolerated, as trial benefits were achieved at these doses 1, 2
• Continue even when eGFR falls below 30 ml/min/1.73 m² 1, 2

Monitoring and Dose Adjustment Algorithm

Initial Monitoring (Within 2-4 Weeks of Starting or Dose Increase)

• Check blood pressure, serum creatinine, and serum potassium 1, 2
• Continue therapy unless serum creatinine rises >30% within 4 weeks 1, 2
• SGLT-2 inhibitor initiation causes reversible eGFR decrease—this is NOT an indication to discontinue 1

Managing Hyperkalemia Without Stopping Therapy

Do not automatically discontinue ACE-I/ARB for hyperkalemia—attempt management strategies first. 1, 2

• Implement potassium binders, dietary potassium restriction, and diuretics 2
• Only reduce dose or discontinue if hyperkalemia remains uncontrolled despite these measures 1, 2

Indications to Reduce or Stop ACE-I/ARB

• Symptomatic hypotension 1, 2
• Uncontrolled hyperkalemia despite medical management 1, 2
• eGFR <15 ml/min/1.73 m² with uremic symptoms requiring symptom control 1

Risk-Stratified Add-On Therapy

Nonsteroidal Mineralocorticoid Receptor Antagonists

For high-risk patients with type 2 diabetes, add nonsteroidal MRA (such as finerenone) when specific criteria are met. 1, 2

• Indication criteria: Type 2 diabetes, eGFR >25 ml/min/1.73 m², normal serum potassium, and persistent albuminuria (>30 mg/g) despite maximum tolerated RAS inhibitor dose 1, 2
• Recent evidence demonstrates that simultaneous initiation of finerenone with SGLT-2 inhibitors produces greater albuminuria reduction than either agent alone (29-32% greater reduction) 3
• Combination therapy does not lead to unexpected adverse events, with uncommon rates of symptomatic hypotension, acute kidney injury, or hyperkalemia requiring discontinuation 3

Additional Essential Therapies

Cardiovascular Risk Reduction

Statin therapy is mandatory for cardiovascular protection in CKD patients. 2, 4

• Prescribe statins for all adults ≥50 years with eGFR <60 ml/min/1.73 m² 2
• Rosuvastatin 5 mg daily (maximum 10 mg daily) is appropriate for CKD stage 3B 4

Volume Management

• Loop diuretics are preferred when eGFR <30 ml/min 2
• Diuretics should be administered in addition to ACE-I/ARB, not as replacement 2

Critical Pitfalls to Avoid

Never prescribe NSAIDs in CKD patients—they significantly increase acute kidney injury risk and accelerate CKD progression. 4

• For inflammatory conditions, use low-dose colchicine or short-course glucocorticoids instead 4
• Do not discontinue RAS inhibitors prematurely for mild hyperkalemia—implement management strategies first 1, 2
• Do not stop SGLT-2 inhibitors due to initial eGFR dip—this is expected and reversible 1

Emerging Combination Therapy Paradigm

The new standard of care involves multi-drug combination therapy targeting different mechanisms of CKD progression. 5, 6

• Each therapeutic class (SGLT-2 inhibitors, RAS inhibitors, nonsteroidal MRAs) offers independent and additive benefits 5
• SGLT-2 inhibitors reduce hyperkalaemia and fluid retention, enhancing tolerability of other treatments 5
• This approach is supported by randomized data showing each class works effectively regardless of background therapy 5