Antihypertensive Dosing in CKD Based on eGFR
Use the highest approved dose of ACE inhibitors or ARBs that is tolerated in CKD patients, as proven benefits were achieved at target doses in clinical trials, and continue these medications even when eGFR falls below 30 mL/min/1.73 m², only considering dose reduction or discontinuation at eGFR <15 mL/min/1.73 m² if symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms develop. 1
First-Line Agent Selection by CKD Stage and Albuminuria
For CKD Stages G1-G4 (eGFR ≥15 mL/min/1.73 m²)
ACE inhibitors or ARBs are first-line therapy for the following patient groups 1:
- Severely increased albuminuria (A3, >300 mg/g) without diabetes: Strong recommendation to start RASi 1
- Moderately increased albuminuria (A2, 30-300 mg/g) without diabetes: Suggested to start RASi 1
- Moderately-to-severely increased albuminuria (A2 or A3) with diabetes: Strong recommendation to start RASi 1
- No albuminuria (A1): May reasonably use RASi for specific indications like hypertension or heart failure 1
SGLT2 Inhibitors as Add-On Therapy
SGLT2 inhibitors should be added for patients meeting these criteria 1:
- Type 2 diabetes with eGFR ≥20 mL/min/1.73 m²: Strong recommendation 1
- eGFR ≥20 mL/min/1.73 m² with urine ACR ≥200 mg/g: Strong recommendation 1
- Heart failure, irrespective of albuminuria level: Strong recommendation 1
- eGFR 20-45 mL/min/1.73 m² with urine ACR <200 mg/g: Suggested 1
Once initiated, continue SGLT2 inhibitors even if eGFR falls below 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1.
Specific Dosing by eGFR Category
eGFR >30 mL/min/1.73 m²
No dose adjustment required for ACE inhibitors or ARBs 2. Use standard dosing:
- Lisinopril: Start 10 mg daily for hypertension, titrate to 20-40 mg daily as tolerated 2
- Target the highest approved dose that is tolerated to achieve maximum renoprotective benefits 1
eGFR 10-30 mL/min/1.73 m² (Stage G4)
Reduce initial dose to half of the usual recommended dose 2:
- Lisinopril for hypertension: Start 5 mg daily, titrate up to maximum 40 mg daily as tolerated 2
- Lisinopril for heart failure: Start 2.5 mg daily, titrate up to maximum 40 mg daily as tolerated 2
- Continue ACE inhibitor/ARB therapy even at this eGFR level unless contraindications develop 1
eGFR <10 mL/min/1.73 m² or Hemodialysis (Stage G5)
Start with 2.5 mg daily for lisinopril 2. Consider reducing dose or discontinuing if 1:
- Symptomatic hypotension occurs
- Uncontrolled hyperkalemia despite medical management
- Uremic symptoms need reduction while treating kidney failure
Critical Monitoring Parameters
Timing of Laboratory Checks
Check serum creatinine and potassium within 2-4 weeks of initiation or dose increase of RASi, with timing dependent on current GFR and baseline potassium 1.
Acceptable Changes After RASi Initiation
Continue ACE inhibitor or ARB unless 1:
- Serum creatinine rises by >30% within 4 weeks of initiation or dose increase
- Symptomatic hypotension develops
- Uncontrolled hyperkalemia persists despite treatment
Hyperkalemia Management Strategy
Manage hyperkalemia with potassium-lowering measures rather than automatically reducing or stopping RASi 1:
- Avoid potassium supplements and potassium-based salt substitutes 3
- Counsel on limiting high-potassium foods 3
- Consider potassium binders if needed
- Only reduce RASi dose if hyperkalemia remains uncontrolled despite these measures 1
Blood Pressure Targets by eGFR
For eGFR ≥30 mL/min/1.73 m²
Target systolic BP <120 mm Hg when tolerated, using standardized office BP measurement 1. This intensive target applies when 1:
- Patient can tolerate the lower target
- BP measurements are obtained in a standardized manner
- Patient does not have very limited life expectancy or symptomatic postural hypotension
For eGFR <30 mL/min/1.73 m²
Target systolic BP 120-130 mm Hg is reasonable, with individualization based on tolerability 1, 4. Less intensive BP-lowering is appropriate for patients with 1:
- Very limited life expectancy
- Symptomatic postural hypotension
Add-On Therapy for Inadequate Control
Second-Line Agents
Add a long-acting dihydropyridine calcium channel blocker or thiazide-like diuretic if BP remains uncontrolled on RASi 4.
For eGFR <30 mL/min/1.73 m²: Use loop diuretics instead of thiazides, as thiazides become ineffective at this level of kidney function 4.
Mineralocorticoid Receptor Antagonists
Nonsteroidal MRA (finerenone) may be added for patients with 1:
- Type 2 diabetes
- eGFR >25 mL/min/1.73 m²
- Normal serum potassium
- Albuminuria >30 mg/g despite maximum tolerated RASi dose
Do not use nonsteroidal MRA at eGFR <25 mL/min/1.73 m² 3. Monitor potassium closely, as MRAs increase hyperkalemia risk, particularly at lower eGFR 1.
Critical Contraindications
Dual or Triple RAS Blockade
Never combine ACE inhibitor + ARB + direct renin inhibitor 1. This triple combination increases adverse events without benefit 4.
Avoid dual RASi therapy (ACE inhibitor + ARB) due to increased risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit 1, 4.
Special Populations
Kidney Transplant Recipients
Use dihydropyridine calcium channel blocker or ARB as first-line antihypertensive in adult kidney transplant recipients 1. Target BP <130/80 mm Hg using standardized office measurement 1.
Pediatric Patients (≥6 years)
For eGFR >30 mL/min/1.73 m²: Start lisinopril 0.07 mg/kg once daily (up to 5 mg total), titrate to maximum 0.61 mg/kg (up to 40 mg) once daily 2.
Lisinopril is not recommended in pediatric patients with eGFR <30 mL/min/1.73 m² 2.
Common Pitfalls to Avoid
Do not automatically discontinue RASi when eGFR declines below 30 mL/min/1.73 m², as continuation provides ongoing cardiovascular and renal protection 1. Only consider discontinuation at eGFR <15 mL/min/1.73 m² if specific complications arise 1.
Do not withhold SGLT2 inhibitors during routine care once initiated, but temporarily withhold during prolonged fasting, surgery, or critical illness when ketosis risk is elevated 1.
Do not apply intensive BP target of <120 mm Hg to non-standardized BP measurements, as this creates potential hazards 1.