What are the 4 pillars of medication for a patient with Chronic Kidney Disease (CKD)?

The 4 Pillars of CKD Medication Management

The four foundational medication pillars for chronic kidney disease are: (1) SGLT2 inhibitors, (2) RAS blockade (ACE inhibitors or ARBs), (3) Statin therapy, and (4) Blood pressure optimization—these form the core therapeutic strategy to reduce cardiovascular events, slow CKD progression, and improve mortality outcomes. 1

Pillar 1: SGLT2 Inhibitors (First-Line for All CKD Patients)

• Initiate SGLT2 inhibitors immediately when eGFR ≥20 mL/min/1.73 m² regardless of diabetes status, as they provide kidney protection, cardiovascular benefits, and reduce heart failure risk independent of glucose control 2, 1
• Continue SGLT2 inhibitors even as eGFR declines below 20 mL/min/1.73 m² until dialysis initiation 1
• For patients with type 2 diabetes and diabetic kidney disease with eGFR ≥20 mL/min/1.73 m² and urinary albumin ≥200 mg/g creatinine, SGLT2 inhibitors reduce CKD progression and cardiovascular events 2
• SGLT2 inhibitors should be the foundational first-line therapy combined with the other pillars 1

Pillar 2: RAS Blockade (ACE Inhibitors or ARBs)

• ACE inhibitors or ARBs are mandatory when albuminuria is present (UACR ≥30 mg/g) and strongly recommended when UACR ≥300 mg/g or eGFR <60 mL/min/1.73 m² 2
• Titrate to the maximum approved tolerated dose for optimal kidney and cardiovascular protection 2, 1
• For patients with diabetes, hypertension, and albuminuria, initiate ACE inhibitor or ARB therapy 2
• Monitor serum creatinine and potassium within 2-4 weeks of initiation or dose increase 2
• Continue therapy unless serum creatinine rises >30% within 4 weeks of initiation—do not discontinue for minor increases (≤30%) in the absence of volume depletion 2
• Manage hyperkalemia with dietary modifications, diuretics, sodium bicarbonate, or GI cation exchangers rather than immediately stopping RAS blockade 2

Pillar 3: Statin Therapy (Cardiovascular Risk Reduction)

• All adults ≥50 years with eGFR <60 mL/min/1.73 m² (CKD G3a-G5) require statin or statin/ezetimibe combination therapy 2, 1
• For adults ≥50 years with eGFR ≥60 mL/min/1.73 m² (CKD G1-G2), initiate statin therapy 2
• For adults 18-49 years with CKD, initiate statin therapy if they have coronary disease, diabetes, prior ischemic stroke, or estimated 10-year cardiovascular risk >10% 2
• Add ezetimibe 10 mg daily if LDL targets are not met or if high ASCVD risk exists 1
• Choose statin-based regimens to maximize absolute LDL cholesterol reduction 2

Pillar 4: Blood Pressure Optimization

• Target systolic BP <120 mmHg for most CKD patients to reduce progression risk and cardiovascular events 2, 1
• When albuminuria is present, ACE inhibitors or ARBs must be the first-line antihypertensive agent 2, 1
• Optimize blood pressure control and reduce blood pressure variability to slow CKD progression 2
• Multiple antihypertensive classes (ACE inhibitor/ARB, dihydropyridine calcium channel blocker, diuretic) are often needed to achieve BP targets 2

Additional Kidney and Heart Protection (Beyond the 4 Pillars)

• Nonsteroidal mineralocorticoid receptor antagonists (finerenone) provide additive kidney and cardiovascular protection beyond SGLT2 inhibitors and RAS blockade for patients at increased cardiovascular risk or unable to use SGLT2 inhibitors 2, 1
• For patients with CKD and UACR ≥300 mg/g, achieve a 30% or greater reduction in urinary albumin to slow CKD progression 2

Critical Medications to Avoid

• NSAIDs (ibuprofen, naproxen, ketorolac) are absolute contraindications in CKD as they cause acute kidney injury and accelerate progression 1, 3
• For symptomatic inflammatory conditions in CKD, use low-dose colchicine or glucocorticoids instead of NSAIDs 2, 3

Monitoring Schedule

• Regular reassessment every 3-6 months includes eGFR, electrolytes, UACR, hemoglobin, and blood pressure 1
• Monitor serum creatinine and potassium within 2-4 weeks after starting or changing RAS blockade dose 2

Essential Lifestyle Modifications

• Smoking cessation is mandatory 1
• Dietary protein intake should be maximum 0.8 g/kg body weight per day for non-dialysis CKD patients 2, 1
• Restrict dietary sodium to <2,300 mg/day 1
• Consider plant-based Mediterranean-style diet to reduce cardiovascular risk 2, 1
• Optimize physical activity and weight management targeting healthy BMI 1

Common Pitfalls to Avoid

• Do not delay initiation of SGLT2 inhibitors—they should be started immediately when eGFR ≥20 mL/min/1.73 m² 1
• Do not discontinue RAS blockade for minor creatinine increases (≤30%)—attempt to manage hyperkalemia medically first 2
• Do not overlook statin therapy as cardiovascular disease is the leading cause of mortality in CKD patients 3, 4
• Do not prescribe NSAIDs even for short-term use in CKD patients 1, 3