When to Avoid or Use with Caution: ACEi/ARBs, SGLT2 Inhibitors, and Statins in CKD
ACE Inhibitors and ARBs: Continue Through Advanced CKD
Continue ACE inhibitors or ARBs even when eGFR falls below 30 mL/min/1.73 m² and only consider dose reduction or discontinuation at eGFR <15 mL/min/1.73 m² (CKD Stage 5) if specific complications develop. 1, 2
No Absolute GFR Cutoff for Discontinuation
- ACEi/ARBs should be continued through CKD stages 1-4 (eGFR ≥15 mL/min/1.73 m²) regardless of GFR decline 1, 2
- There is no serum creatinine level that automatically contraindicates ACE inhibitor or ARB use 2
- The 2024 KDIGO guidelines explicitly state to continue these medications even when eGFR falls below 30 mL/min/1.73 m² 1, 2
Specific Threshold for Consideration of Discontinuation (CKD Stage 5)
Consider reducing dose or discontinuing ACEi/ARB only when eGFR <15 mL/min/1.73 m² AND one of the following conditions is present: 1, 2
- Symptomatic hypotension
- Uncontrolled hyperkalemia despite medical treatment (dietary restriction, diuretics, sodium bicarbonate, potassium binders)
- Uremic symptoms requiring palliation
Managing Common Concerns Without Stopping Therapy
Acceptable creatinine rise: Continue ACEi/ARB unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 1, 2
- A creatinine rise up to 30% reflects the desired hemodynamic effect of reducing intraglomerular pressure, not acute kidney injury 2
Hyperkalemia management: Implement potassium-lowering measures rather than immediately discontinuing ACEi/ARB 1, 2
- Dietary potassium restriction (limit processed foods rich in bioavailable potassium)
- Loop diuretics (preferred in advanced CKD)
- Sodium bicarbonate supplementation
- Gastrointestinal cation exchangers (potassium binders)
Monitoring Protocol
- Check serum creatinine and potassium within 2-4 weeks after initiation or dose increase 1, 2
- Earlier monitoring (within 1 week) is recommended for patients with baseline eGFR <30 mL/min/1.73 m² or potassium >4.5 mEq/L 2
Critical Pitfall to Avoid
Never combine ACE inhibitor + ARB + direct renin inhibitor - this combination increases adverse events (hyperkalemia, acute kidney injury) without additional benefit 1
SGLT2 Inhibitors: Use Through Advanced CKD
SGLT2 inhibitors should be initiated in patients with CKD and eGFR ≥20 mL/min/1.73 m² and can be continued even if eGFR falls below 20 mL/min/1.73 m² once started. 1
Initiation Thresholds by CKD Stage
Strong recommendation (1A) for initiation when eGFR ≥20 mL/min/1.73 m² in: 1
- Type 2 diabetes with CKD
- Adults with CKD and urine albumin-to-creatinine ratio (ACR) ≥200 mg/g (≥20 mg/mmol)
- Adults with CKD and heart failure, irrespective of albuminuria level
Suggested use (2B) for: 1
- Adults with eGFR 20-45 mL/min/1.73 m² and urine ACR <200 mg/g (<20 mg/mmol)
Continuation Below Initiation Threshold
- Once an SGLT2 inhibitor is initiated, it is reasonable to continue even if eGFR falls below 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1
- The reversible decrease in eGFR on initiation does not necessitate discontinuation 1
When to Temporarily Withhold
Withhold SGLT2 inhibitors during: 1
- Prolonged fasting
- Surgery
- Critical medical illness (when patients may be at greater risk for ketosis)
No Absolute Contraindication at Any CKD Stage
- SGLT2 inhibitors are not contraindicated at any specific CKD stage based on eGFR alone 1
- The primary limitation is initiation below eGFR 20 mL/min/1.73 m², but continuation is acceptable 1
Statins: Different Rules for Dialysis vs. Non-Dialysis CKD
Statins should be used in CKD stages 1-4 but have different recommendations for CKD stage 5 depending on dialysis status. 1, 3
CKD Stages 1-4 (Not on Dialysis)
Initiate statins in adults 40-75 years with LDL-C 70-189 mg/dL and 10-year ASCVD risk ≥7.5% - CKD is a risk-enhancing factor favoring statin initiation 1
- Reduced eGFR (<60 mL/min/1.73 m²) and albuminuria (ACR ≥30 mcg/mg) are independently associated with elevated ASCVD risk 1
- Absolute benefit from statin use is consistent across eGFR stages in non-dialysis CKD 1
CKD Stage 5 Not Yet on Dialysis
All patients aged ≥50 years with CKD Stage 5 (not yet on chronic dialysis) should receive treatment with a statin or statin/ezetimibe combination to reduce cardiovascular mortality 3
- This recommendation applies even with eGFR <15 mL/min/1.73 m² if not yet on dialysis 3
CKD Stage 5 on Dialysis: Do Not Initiate
In adults with advanced kidney disease requiring dialysis treatment, initiation of a statin is NOT recommended (Class III: No Benefit) 1
- Two large-scale randomized controlled trials demonstrated lack of benefit from statin initiation in dialysis patients 1
- The proportion of deaths due to atherosclerotic events is lower in dialysis patients, raising the question of competing risks 1
However, if already on a statin when dialysis starts: It may be reasonable to continue the statin rather than discontinue it 1, 3
- In the SHARP trial, >30% of patients transitioned to dialysis, and proportional effects on major atherosclerotic events were similar in patients on dialysis versus those not on dialysis 1
Monitoring Considerations
Statins carry increased risk of myopathy and rhabdomyolysis in CKD - risk factors include renal impairment, age ≥65 years, and higher statin doses 4
- Monitor for unexplained muscle pain, tenderness, or weakness 4
- Consider testing liver enzymes before initiating therapy and as clinically indicated 4
Summary Algorithm by CKD Stage
CKD Stages 1-3 (eGFR ≥30 mL/min/1.73 m²)
- ACEi/ARBs: Continue without restriction 1
- SGLT2i: Initiate if indicated (diabetes, albuminuria, heart failure) 1
- Statins: Initiate based on cardiovascular risk 1
CKD Stage 4 (eGFR 15-29 mL/min/1.73 m²)
- ACEi/ARBs: Continue without restriction 1
- SGLT2i: Initiate if eGFR ≥20 mL/min/1.73 m² and indicated 1
- Statins: Continue or initiate if not on dialysis 1, 3
CKD Stage 5 (eGFR <15 mL/min/1.73 m²) Not on Dialysis
- ACEi/ARBs: Continue unless symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms 1, 2
- SGLT2i: Continue if already started; consider initiation if eGFR ≥20 mL/min/1.73 m² 1
- Statins: Initiate if age ≥50 years and not yet on dialysis 3