What are the stepwise treatment approaches for a patient with Chronic Kidney Disease (CKD)?

Stepwise Treatment Approach for Chronic Kidney Disease

All patients with CKD should receive SGLT2 inhibitors as foundational first-line therapy combined with maximum-dose RAS inhibition (ACE inhibitor or ARB) when hypertension or albuminuria is present, targeting systolic blood pressure <120 mmHg, alongside statin therapy—this comprehensive strategy forms the core of modern CKD management to reduce kidney disease progression and cardiovascular mortality. 1, 2, 3

Step 1: Foundation - Lifestyle Modifications (All Patients)

• Physical activity: 150 minutes per week of moderate-intensity exercise, adjusted to cardiovascular and physical tolerance 2, 4, 3
• Diet: Adopt a plant-based "Mediterranean-style" diet with higher consumption of plant-based foods and lower consumption of ultra-processed foods 1, 2, 3
• Protein intake: Maintain 0.8 g/kg body weight/day in CKD G3-G5; avoid high protein intake >1.3 g/kg/day as it accelerates progression 2, 3
• Weight management: Achieve optimal body mass index through weight loss if obese 4, 3
• Smoking cessation: Complete cessation of all tobacco products 4

Step 2: First-Line Pharmacologic Therapy (Initiate Immediately)

A. SGLT2 Inhibitors (Universal First-Line)

• Initiate in ALL CKD patients regardless of diabetes status when eGFR ≥20 mL/min/1.73 m² 1, 2, 3
• Continue until dialysis or transplantation 2, 3
• This represents the most significant advancement in CKD management with robust evidence for delaying progression and reducing cardiovascular complications 3

B. RAS Inhibition (ACE Inhibitor or ARB)

• Mandatory when albuminuria is present (any level ≥30 mg/g) 1, 2, 3
• First-line when hypertension exists 2, 3
• Titrate to maximum tolerated dose to maximize kidney protection 3
• Do not discontinue due to modest creatinine elevation (up to 30% increase acceptable) 4

C. Statin Therapy

• All adults ≥50 years with eGFR <60 mL/min/1.73 m² (CKD G3a-G5): Statin or statin/ezetimibe combination 1, 2
• Adults ≥50 years with eGFR ≥60 mL/min/1.73 m² (CKD G1-G2): Statin therapy 1
• Adults 18-49 years: Statin if coronary disease, diabetes, prior ischemic stroke, or 10-year cardiovascular risk >10% 1, 4
• Choose regimens that maximize absolute LDL cholesterol reduction 1, 3

Step 3: Blood Pressure Targets (Aggressive Control)

• Target systolic BP <120 mmHg for most CKD patients 1, 2, 4, 3
• With albuminuria ≥30 mg/24h: Target <130/80 mmHg with ACE inhibitor or ARB as mandatory first-line 3
• Without albuminuria: Target <140/90 mmHg 3
• Add dihydropyridine calcium channel blockers and/or diuretics if needed to achieve targets 4

Step 4: Additional Drugs with Heart and Kidney Protection (Based on Residual Risk)

A. For Type 2 Diabetes Patients

• GLP-1 receptor agonists: Preferred glucose-lowering drug if SGLT2i and metformin insufficient to meet glycemic targets 1, 2, 3
• Metformin: When eGFR ≥30 mL/min/1.73 m² 1
• Nonsteroidal mineralocorticoid receptor antagonists (ns-MRA): Add for patients with persistent albuminuria >30 mg/g (>3 mg/mmol) despite first-line therapy 1, 2

B. Advanced Lipid Management

• Ezetimibe: Add to statin based on ASCVD risk and lipid levels 2
• PCSK9 inhibitors: Consider for patients with indication for use 1, 2

C. Antiplatelet Therapy

• Low-dose aspirin: For secondary prevention in established ischemic cardiovascular disease 1, 2, 3
• P2Y12 inhibitors: Alternative if aspirin intolerance 1

D. Anticoagulation (If Atrial Fibrillation)

• NOACs preferred over warfarin in CKD G1-G4 for thromboprophylaxis 3

Step 5: Regular Monitoring and Reassessment

• Risk factor reassessment every 3-6 months 1, 2
• Monitor serum creatinine, potassium, and albuminuria regularly 4
• Estimate 10-year cardiovascular risk using validated risk tools 1, 2, 3

Step 6: Specialist Referral Criteria

Refer to nephrology when: 3

• ACR ≥30 mg/g (3 mg/mmol) or PCR ≥200 mg/g (20 mg/mmol)
• Persistent hematuria
• Any sustained decrease in eGFR
• eGFR <30 mL/min/1.73 m² (high risk of progression)

Critical Pitfalls to Avoid

• NEVER prescribe NSAIDs in CKD due to nephrotoxicity risk and potential for acute kidney injury—use low-dose colchicine or glucocorticoids instead for inflammatory conditions like acute gout 2, 3
• Do NOT discontinue RAS inhibitors due to modest increases in serum creatinine (up to 30% acceptable) or potassium unless specific contraindications 4, 3
• Do NOT use agents to lower serum uric acid in asymptomatic hyperuricemia to delay CKD progression 2, 3
• Do NOT delay SGLT2 inhibitors—they have shown significant benefits in slowing CKD progression and should be started immediately 4
• Review all medications for appropriate dosing and avoid nephrotoxins 4, 3