What is the stepwise management approach for chronic kidney disease, including recommended drugs and doses?

Chronic Kidney Disease: Stepwise Management with Drugs and Doses

All CKD patients should immediately receive SGLT2 inhibitors as foundational first-line therapy when eGFR ≥20 mL/min/1.73 m², combined with RAS inhibition (ACE inhibitor or ARB) when hypertension or albuminuria is present, plus statin therapy—forming the core triad of kidney and cardiovascular protection. 1

Step 1: Initiate SGLT2 Inhibitors (First-Line for All CKD)

SGLT2 inhibitors are mandatory first-line therapy regardless of diabetes status:

• Canagliflozin 100 mg daily OR Dapagliflozin 10 mg daily OR Empagliflozin 10 mg daily 1, 2
• Start when eGFR ≥20 mL/min/1.73 m² and continue until dialysis initiation or transplantation 1, 3
• Continue even as eGFR declines below 20 mL/min/1.73 m² until dialysis 1
• These agents slow GFR decline, reduce albuminuria, and provide cardiovascular protection independent of glucose-lowering effects 2

Step 2: Add RAS Inhibition for Blood Pressure and Proteinuria Control

ACE inhibitors or ARBs are mandatory when albuminuria ≥30 mg/24 hours is present:

• ACE inhibitors (e.g., lisinopril, enalapril, ramipril) OR ARBs (e.g., losartan, valsartan, irbesartan) 4
• Titrate to maximum tolerated dose for optimal kidney and cardiovascular protection 1
• Use in all patients with urine albumin excretion >300 mg/24 hours (1B recommendation) 4

Blood pressure targets based on albuminuria status:

• If albuminuria <30 mg/24 hours: Target BP ≤140/90 mmHg 4
• If albuminuria ≥30 mg/24 hours: Target BP ≤130/80 mmHg 4
• Optimal target for most CKD patients: Systolic BP <120 mmHg to reduce progression risk 1

Critical warning: Do NOT combine ACE inhibitors with ARBs—insufficient evidence supports this combination and may increase harm 4

Step 3: Add Statin Therapy for Cardiovascular Protection

All CKD patients ≥50 years require statin therapy:

• If eGFR <60 mL/min/1.73 m² (stages G3a-G5): Statin or statin/ezetimibe combination (1A recommendation) 4, 1
• If eGFR ≥60 mL/min/1.73 m² (stages G1-G2): Statin alone (1B recommendation) 4
• Moderate-to-high intensity dosing: Atorvastatin 40-80 mg daily OR Rosuvastatin 20-40 mg daily 3
• Add ezetimibe 10 mg daily if LDL targets not met or high ASCVD risk 1, 3

For patients 18-49 years: Consider statin if coronary disease, diabetes, prior stroke, or 10-year cardiovascular risk >10% 4

Step 4: Consider Advanced Kidney Protection

Nonsteroidal mineralocorticoid receptor antagonists (MRAs):

• Finerenone provides additive kidney and cardiovascular protection beyond SGLT2 inhibitors and RAS blockade 1
• Consider in patients with persistent albuminuria despite SGLT2i and RAS inhibition 1

Step 5: Implement Mandatory Lifestyle Modifications

These interventions are linked to reduced proteinuria and slowed CKD progression:

• Sodium restriction: <2 g (2,000 mg) per day 4, 1
• Protein intake: 0.8 g/kg body weight per day for non-dialysis CKD patients; avoid high protein intake >1.3 g/kg/day 1
• Target BMI: 20-25 kg/m² through weight management 4, 1
• Exercise: 30 minutes, 5 times per week 4
• Smoking cessation: Mandatory 4, 1
• Diabetes control: Target HbA1c 7% 4
• Plant-based Mediterranean-style diet to reduce cardiovascular risk 4, 1

Step 6: Manage CKD-Specific Complications

Anemia management:

• Monitor hemoglobin regularly; treat when below target levels 1
• Iron supplementation before or with erythropoiesis-stimulating agents 1

Metabolic acidosis:

• Monitor serum bicarbonate regularly 1
• Oral alkali supplementation to maintain normal serum bicarbonate 1

Electrolyte management:

• Monitor serum potassium, especially with RAS inhibitors, diuretics, or MRAs 1
• Individualize dietary potassium restrictions based on serum levels 1

Step 7: Cardiovascular Disease Prevention

Secondary prevention (established cardiovascular disease):

• Aspirin 81 mg daily for lifelong secondary prevention (1C recommendation) 4, 1
• Consider P2Y12 inhibitors if aspirin intolerance 4

All CKD patients are at increased risk for acute kidney injury (AKI): Awareness and prevention strategies are critical (1A recommendation) 4

Step 8: Monitoring Schedule

Regular reassessment every 3-6 months includes: 1

• eGFR and serum creatinine
• Electrolytes (sodium, potassium, bicarbonate)
• Urine albumin-to-creatinine ratio
• Hemoglobin
• Blood pressure
• Lipid panel

Progression is defined as: Change in GFR category PLUS ≥25% decline in eGFR 4

Step 9: Nephrology Referral Criteria

Immediate referral to nephrology when: 1, 5

• eGFR <30 mL/min/1.73 m² (stages 4-5)
• Albuminuria ≥300 mg per 24 hours
• Rapid decline in eGFR
• Uncontrolled hypertension despite multiple agents
• Persistent electrolyte abnormalities

Delaying nephrology referral for advanced CKD leads to poor outcomes 1

Critical Medications to AVOID in CKD

Absolute contraindications: 1

• NSAIDs (ibuprofen/Advil, naproxen/Aleve, ketorolac/Toradol)—cause acute kidney injury and accelerate progression
• Metformin when eGFR <30 mL/min/1.73 m²—risk of lactic acidosis 3, 2

Use with extreme caution:

• Sulfonylureas—increased hypoglycemia risk in CKD 3, 2
• All opioids—reduce doses and frequency in renal impairment 4
• Fentanyl and buprenorphine are safest opioids in CKD stages 4-5 (eGFR <30 mL/min) 4

Special Considerations for Diabetes and CKD

If patient has diabetes:

• SGLT2 inhibitors remain first-line for both glycemic control and kidney protection 2
• Metformin can be used if eGFR ≥30 mL/min/1.73 m²; reduce to 1000 mg daily if eGFR 30-44 mL/min/1.73 m² 2
• GLP-1 receptor agonists for patients not meeting glycemic targets or with obesity 2
• Avoid sulfonylureas when possible due to hypoglycemia risk; if needed, glipizide is preferred 2
• Insulin doses may require 25-50% reduction when eGFR <45 mL/min/1.73 m² 3, 2

Common Pitfalls to Avoid

• Overlooking lifestyle modifications alongside pharmacotherapy leads to suboptimal outcomes 1
• Failing to prepare patients for renal replacement therapy in a timely manner 1
• Neglecting to screen for and manage CKD complications until severe 1
• Not adjusting medication doses for kidney function 1
• Continuing nephrotoxic medications (especially NSAIDs) 5

Integrated Team Approach

Implement multidisciplinary care with: 1

• Nephrologists
• Primary care providers
• Dietitians
• Pharmacists
• Other specialists as needed

Prioritize patient concerns, values, and preferences in all treatment decisions 1