Antihypertensive Medications for Chronic Kidney Disease
For patients with CKD and albuminuria, start with an ACE inhibitor or ARB at the highest tolerated dose, targeting a systolic blood pressure <120 mmHg when tolerated. 1
First-Line Therapy: RAS Inhibitors
ACE inhibitors or ARBs are the cornerstone of antihypertensive therapy in CKD patients with albuminuria:
- For CKD with severely increased albuminuria (A3) without diabetes: Start RAS inhibitors (ACEi or ARB) - this is a strong recommendation 1
- For CKD with moderately increased albuminuria (A2) without diabetes: Start RAS inhibitors (ACEi or ARB) 1
- For CKD with moderately-to-severely increased albuminuria (A2 or A3) with diabetes: Start RAS inhibitors (ACEi or ARB) - this is a strong recommendation 1
Dosing strategy: Use the highest approved dose that is tolerated, as proven benefits in clinical trials were achieved at these doses 1
For CKD Without Albuminuria
- For CKD patients with normal to mildly increased albuminuria (A1): Consider RAS inhibitors for specific indications such as treating hypertension or heart failure with reduced ejection fraction 1
Blood Pressure Targets
Target systolic blood pressure <120 mmHg using standardized office BP measurement when tolerated 1, 2
Important caveats:
- Consider less intensive BP-lowering in patients with frailty, high fall risk, very limited life expectancy, or symptomatic postural hypotension 1
- Check for postural hypotension regularly when treating with BP-lowering drugs 1
Monitoring RAS Inhibitor Therapy
Check BP, serum creatinine, and potassium within 2-4 weeks of initiation or dose increase 1, 3
Continue therapy unless:
- Serum creatinine rises >30% within 4 weeks of initiation or dose increase 1, 3
- Symptomatic hypotension occurs 1
- Uncontrolled hyperkalemia persists despite medical management 1
- eGFR <15 mL/min/1.73 m² with uremic symptoms requiring dose reduction 1
Key practice point: Hyperkalemia can often be managed by measures to reduce serum potassium levels rather than stopping the RAS inhibitor 1, 3
Continue ACEi or ARB even when eGFR falls below 30 mL/min/1.73 m² 1
Critical Contraindication
Never combine ACE inhibitor + ARB + direct renin inhibitor in any patient with CKD - this is strongly contraindicated 1, 3
Second-Line and Add-On Therapy
When additional BP lowering is needed beyond RAS inhibitors:
Add dihydropyridine calcium channel blockers or thiazide/thiazide-like diuretics 3, 4, 5
For resistant hypertension:
- Consider adding low-dose spironolactone with close monitoring of potassium and renal function 1, 3, 5
- Chlorthalidone is effective in stage 4 CKD with uncontrolled hypertension and can mitigate hyperkalemia risk 5
Non-dihydropyridine calcium channel blockers consistently reduce albuminuria and slow kidney function decline, but should not be used as monotherapy in proteinuric CKD - always combine with a RAS blocker 4
Special Populations
Kidney Transplant Recipients
Use dihydropyridine calcium channel blocker or ARB as first-line therapy 1, 3
Pediatric CKD
- Target 24-hour mean arterial pressure ≤50th percentile for age, sex, and height using ambulatory BP monitoring 1
- Use ACEi or ARB as first-line therapy 1
Patients with Hepatic Impairment
- Start losartan at 25 mg once daily in mild-to-moderate hepatic impairment 6
Lifestyle Modifications
Sodium restriction to <2 g/day (<90 mmol/day or <5 g sodium chloride/day) 1, 2
Exception: Avoid sodium restriction in patients with sodium-wasting nephropathy 1
Additional measures: Moderate-intensity physical activity for at least 150 minutes per week 2
Common Pitfalls to Avoid
- Don't stop RAS inhibitors prematurely for mild creatinine elevations - up to 30% increase within 4 weeks is acceptable 1, 3
- Don't discontinue RAS inhibitors solely for hyperkalemia - implement potassium-lowering strategies first 1, 3
- Don't use dual or triple RAS blockade - this increases adverse events without additional benefit 1, 3
- Don't use dihydropyridine CCBs as monotherapy in proteinuric CKD - always combine with RAS inhibitor 4