What are the treatment options for Stage 2 Chronic Kidney Disease (CKD)?

Stage 2 CKD Treatment

For Stage 2 CKD (eGFR 60-89 mL/min/1.73 m² with kidney damage), treatment focuses on comprehensive cardiovascular-kidney risk reduction through lifestyle modifications, blood pressure control, and addressing underlying causes, with pharmacotherapy guided by the presence of diabetes, hypertension, and albuminuria. 1

Risk Assessment and Monitoring

• Assess for albuminuria using spot urine albumin-to-creatinine ratio (UACR) at least annually, as this determines treatment intensity and guides medication selection 2, 3
• Monitor eGFR, electrolytes, and blood pressure every 3-6 months to track disease progression and medication effects 1, 4
• Calculate 10-year cardiovascular risk using validated tools, as cardiovascular disease is the leading cause of mortality in CKD patients 4

Lifestyle Modifications (Foundation for All Patients)

• Implement moderate-intensity physical activity for at least 150 minutes per week (e.g., brisk walking, cycling), avoiding sedentary behavior 1
• Adopt a plant-based Mediterranean-style diet with sodium restriction to <2,300 mg/day (<5 g sodium chloride) 1, 4
• Maintain protein intake at 0.8 g/kg body weight per day, avoiding high protein intake >1.3 g/kg/day which accelerates kidney function decline 4
• Achieve and maintain healthy body weight through diet and exercise, particularly if BMI is elevated 1, 4
• Mandatory smoking cessation for all tobacco users, as smoking accelerates CKD progression 1, 4
• Limit alcohol intake to reduce inflammatory burden and cardiovascular risk 4, 5

Pharmacotherapy Based on Clinical Characteristics

For Patients WITH Diabetes and Stage 2 CKD

First-line therapy requires a comprehensive multi-drug approach:

• Initiate SGLT2 inhibitor immediately (e.g., empagliflozin, dapagliflozin, canagliflozin) when eGFR ≥20 mL/min/1.73 m², regardless of glycemic control, for kidney and cardiovascular protection 1, 4
• Start metformin for glycemic control when eGFR ≥30 mL/min/1.73 m², beginning with 500-850 mg once daily and titrating upward every 7 days to maximum tolerated dose 1
• Add GLP-1 receptor agonist (e.g., dulaglutide, semaglutide, liraglutide) if glycemic targets are not met with metformin and SGLT2i, or if these agents cannot be used, as GLP-1 RAs reduce cardiovascular events and slow albuminuria progression 1

If hypertension AND/OR albuminuria (UACR >30 mg/g) are present:

• Initiate ACE inhibitor or ARB (e.g., lisinopril 10-40 mg daily, losartan 50-100 mg daily) and titrate to maximum tolerated dose 1
• Monitor serum creatinine and potassium 2-4 weeks after initiation or dose change; continue therapy unless creatinine increases >30% or uncontrolled hyperkalemia develops 1
• Target blood pressure <130/80 mmHg when albuminuria is present 1

For persistent albuminuria despite SGLT2i and RAS blockade:

• Consider adding nonsteroidal mineralocorticoid receptor antagonist (finerenone 10-20 mg daily) for additional kidney and cardiovascular protection in type 2 diabetes with UACR >30 mg/g 1, 4

For Patients WITHOUT Diabetes and Stage 2 CKD

If hypertension AND albuminuria (UACR >30 mg/g) are present:

• Initiate ACE inhibitor or ARB as first-line antihypertensive and titrate to maximum tolerated dose 1, 6
• Target blood pressure <130/80 mmHg when albuminuria is present 1, 4
• Monitor serum creatinine and potassium 2-4 weeks after initiation or dose change 1

If hypertension WITHOUT albuminuria:

• Use any antihypertensive agent (ACE inhibitor, ARB, calcium channel blocker, or thiazide diuretic), as RAS inhibitors have not proven kidney-protective benefits without albuminuria 1
• Target blood pressure <140/90 mmHg when albuminuria is absent 1

If albuminuria WITHOUT hypertension:

• Consider ACE inhibitor or ARB given the strong association between albuminuria and kidney disease progression, despite limited clinical trial evidence in normotensive patients 1

For non-diabetic CKD with eGFR ≥20 mL/min/1.73 m²:

• Consider SGLT2 inhibitor for kidney protection, as recent evidence supports use regardless of diabetes status 4

Cardiovascular Risk Reduction (All Stage 2 CKD Patients)

• Initiate statin therapy (e.g., atorvastatin 20-40 mg daily, rosuvastatin 5-10 mg daily) for all adults ≥50 years with CKD, regardless of baseline LDL cholesterol 1, 4
• Add ezetimibe 10 mg daily if LDL targets are not met or if high ASCVD risk exists 4
• Aspirin 81 mg daily for secondary prevention in established cardiovascular disease (lifelong); consider for primary prevention in high ASCVD risk patients 4

Medications to Absolutely Avoid

• Never prescribe NSAIDs (ibuprofen, naproxen, ketorolac) even for short-term use, as they cause acute kidney injury and accelerate CKD progression 7, 4, 3
• Avoid combination ACE inhibitor + ARB therapy, as this is harmful and increases adverse events without additional benefit 1

Management of RAS Inhibitor Side Effects

If cough develops with ACE inhibitor:

• Switch to ARB as an acceptable alternative 1

If hyperkalemia develops (potassium >5.5 mEq/L):

• Moderate dietary potassium intake, initiate diuretic, use sodium bicarbonate if metabolic acidosis present, or add gastrointestinal cation exchanger before discontinuing RAS inhibitor 1

If serum creatinine increases during initiation/titration:

• Continue RAS inhibitor unless creatinine increases >30% from baseline 1

Discontinue or reduce dose if:

• Symptomatic hypotension, uncontrolled hyperkalemia despite interventions, or acute kidney injury occurs 1

Common Pitfalls to Avoid

• Delaying SGLT2 inhibitor initiation in diabetic CKD until glycemic control worsens, when it should be started immediately for kidney and cardiovascular protection regardless of HbA1c 1
• Failing to titrate RAS inhibitors to maximum tolerated dose, which is necessary for optimal kidney protection 1
• Prematurely discontinuing RAS inhibitors for mild creatinine elevations (<30% increase) or mild hyperkalemia that can be managed with dietary modification or adjunctive therapies 1
• Overlooking statin therapy, which is mandatory for cardiovascular risk reduction in all CKD patients ≥50 years 1, 4
• Neglecting lifestyle modifications while focusing solely on pharmacotherapy, when diet, exercise, and smoking cessation are foundational 1, 4
• Using RAS inhibitors as first-line therapy in hypertensive patients without albuminuria, when other antihypertensives are equally effective for cardiovascular risk reduction 1