What are the pillars of Chronic Kidney Disease (CKD) management?

The Four Pillars of CKD Management

Modern CKD management rests on four evidence-based pillars: (1) SGLT2 inhibitor therapy, (2) RAAS inhibition with ACE inhibitors or ARBs, (3) blood pressure control targeting <120 mmHg systolic, and (4) statin-based cardiovascular risk reduction. 1

Pillar 1: SGLT2 Inhibitor Therapy (First-Line for Most Patients)

SGLT2 inhibitors are now first-line therapy for most CKD patients and should be continued until dialysis or transplant. 1

Specific Indications:

• Strongly recommended (Grade 1A) for patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² 2
• Strongly recommended (Grade 1A) for adults with eGFR ≥20 mL/min/1.73 m² with urine ACR ≥200 mg/g (≥20 mg/mmol), regardless of diabetes status 2
• Strongly recommended (Grade 1A) for patients with heart failure, irrespective of albuminuria level 2
• Suggested (Grade 2B) for adults with eGFR 20-45 mL/min/1.73 m² with urine ACR <200 mg/g 2

Key Implementation Points:

• Once initiated, continue SGLT2i even if eGFR falls below 20 mL/min/1.73 m² unless not tolerated or kidney replacement therapy is initiated 2
• Withhold temporarily during prolonged fasting, surgery, or critical illness due to ketosis risk 2
• The reversible eGFR decrease on initiation is not an indication to discontinue 2

Pillar 2: RAAS Inhibition (ACE Inhibitor or ARB)

ACE inhibitors or ARBs at maximum tolerated dose are mandatory when albuminuria is present and first-line when hypertension exists. 1

Specific Indications by Albuminuria Level:

• Strongly recommended (Grade 1B) for severely increased albuminuria (A3, >300 mg/24 hours) in both diabetic and non-diabetic patients 2
• Suggested (Grade 2C) for moderately increased albuminuria (A2, 30-299 mg/g) without diabetes 2
• Strongly recommended (Grade 1B) for moderately-to-severely increased albuminuria (A2 and A3) with diabetes 2

Critical Dosing and Monitoring:

• Administer the highest approved dose tolerated, as proven benefits were achieved using these doses in trials 2
• Check BP, serum creatinine, and potassium within 2-4 weeks of initiation or dose increase 2
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation 2
• Continue even when eGFR falls below 30 mL/min/1.73 m² 2
• Never combine ACE inhibitor + ARB + direct renin inhibitor (Grade 1B) as dual/triple RAAS blockade increases adverse events without benefit 2

Managing Common Concerns:

• Hyperkalemia can often be managed with potassium-lowering measures rather than stopping RAAS inhibition 2
• Consider dose reduction or discontinuation only for symptomatic hypotension, uncontrolled hyperkalemia despite treatment, or uremic symptoms with eGFR <15 mL/min/1.73 m² 2

Pillar 3: Blood Pressure Control

Target systolic BP <120 mmHg for most CKD patients. 1

BP Targets by Albuminuria Status:

• For albuminuria <30 mg/24 hours: Maintain BP ≤140/90 mmHg (Grade 1B) 2
• For albuminuria ≥30 mg/24 hours: Maintain BP ≤130/80 mmHg (Grade 2D) 2
• Current optimal target: <120 mmHg systolic for most patients 1

First-Line Agent Selection:

• When albuminuria is present, ACE inhibitor or ARB must be first-line 1
• RAAS interruption slows progression of both diabetic and non-diabetic nephropathy 2

Lifestyle Interventions Supporting BP Control:

• Sodium restriction to <2 g per day 2
• Achieve BMI 20-25 kg/m² 2
• Exercise 30 minutes 5 times per week (or 150 minutes weekly moderate-intensity) 2, 1
• Smoking cessation 2

Pillar 4: Statin-Based Cardiovascular Risk Reduction

Moderate-to-high intensity statin therapy is recommended for all adults ≥50 years with eGFR <60 mL/min/1.73 m² (CKD G3a-G5). 1

Rationale:

• CKD patients are more likely to experience cardiovascular events than progress to end-stage renal disease 2
• They have worse prognosis with higher mortality after acute MI and increased risk for recurrent MI, heart failure, and sudden cardiac death 2

Lipid Management Strategy:

• Use statin or statin/ezetimibe combination 1
• Add ezetimibe and PCSK9 inhibitors based on ASCVD risk and lipid levels 1

Additional Critical Management Components

Nonsteroidal Mineralocorticoid Receptor Antagonists (ns-MRA):

• Suggested (Grade 2A) for adults with type 2 diabetes, eGFR >25 mL/min/1.73 m², normal potassium, and albuminuria >30 mg/g despite maximum tolerated RAAS inhibition 2
• Most appropriate for high-risk patients with persistent albuminuria despite standard-of-care therapies 2
• Can be added to RASi and SGLT2i for treatment of type 2 diabetes and CKD 2

Diabetes Management:

• Target HbA1c of 7% 2
• Use GLP-1 receptor agonists where indicated 1

Dietary Modifications:

• Protein intake 0.8 g/kg body weight/day for CKD G3-G5 1
• Adopt plant-based diets with lower consumption of ultraprocessed foods 1

Cardiovascular Disease Management:

• Low-dose aspirin for secondary prevention in established ischemic cardiovascular disease 1
• NOACs preferred over warfarin for atrial fibrillation in CKD G1-G4 1

Monitoring and Risk Stratification

Monitoring Frequency by GFR and Albuminuria:

• The intensity of monitoring increases with worsening GFR category and albuminuria level 2
• Regular risk factor reassessment every 3-6 months 1
• For severely increased albuminuria (≥300 mg/g): monitor 3-4 times per year 2

Defining CKD Progression:

• Requires both a change in GFR category AND ≥25% decrease in eGFR to avoid misinterpreting small fluctuations 2
• Increasing albuminuria suggests progression and associates with increased risk for adverse outcomes 2

Critical Pitfalls to Avoid

Nephrotoxin Avoidance:

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. 1

Medication Errors:

• Do NOT use agents to lower serum uric acid in asymptomatic hyperuricemia to delay CKD progression 1
• Avoid high protein intake (>1.3 g/kg/day) as it accelerates progression 1
• Never combine ACE inhibitor + ARB as evidence is insufficient and adverse events increase 2

AKI Awareness:

• All people with CKD are at increased risk of AKI (Grade 1A) 2
• CKD remains an independent risk factor for AKI even after adjustment for comorbidities 2
• AKI is itself a risk factor for both incident CKD and CKD progression 2

Cardiovascular Care Equity:

• The level of care for ischemic heart disease offered to CKD patients should not be prejudiced by their CKD (Grade 1A) 2
• Despite higher cardiovascular risk, CKD patients frequently receive suboptimal care 2