Can ARBs Cause BUN Elevation?
Yes, ARBs can cause BUN elevation through their hemodynamic effects on the kidney, but this is an expected physiological response—not kidney injury—and should not prompt discontinuation of therapy in most cases.
Mechanism and Expected Changes
ARBs alter intrarenal hemodynamics by reducing glomerular filtration pressure, which leads to predictable increases in both BUN and serum creatinine 1. This occurs because ARBs reduce efferent arteriolar tone, decreasing intraglomerular pressure and consequently lowering the glomerular filtration rate 1. These changes reflect the drug's mechanism of action rather than true acute kidney injury 1.
What Degree of Elevation is Acceptable?
Creatinine increases up to 30% from baseline with ARB therapy are expected, acceptable, and should not be confused with acute kidney injury 1. The 2023 American Diabetes Association guidelines explicitly state that ARBs should not be discontinued for increases in serum creatinine less than 30% in the absence of volume depletion 1.
Key thresholds from the 2012 European Society of Cardiology guidelines 1:
- Acceptable: Creatinine increase up to 50% above baseline or up to 266 μmol/L (3 mg/dL), whichever is smaller
- Acceptable: Potassium ≤5.5 mmol/L
- Action required: Creatinine increase >100% or >310 μmol/L (3.5 mg/dL) or eGFR <20 mL/min/1.73 m²
Clinical Evidence Supporting Continuation
The ACCORD BP trial demonstrated that patients with up to 30% increases in serum creatinine during intensive blood pressure lowering (which included ARB use) had no increase in mortality or progressive kidney disease 1. Importantly, markers of true acute kidney injury did not increase despite the creatinine elevation 1.
When to Be Concerned
Do not confuse hemodynamic changes with true kidney injury 1. Investigate and potentially adjust therapy if:
- Volume depletion is present 1
- Concomitant nephrotoxic medications (NSAIDs, contrast) are being used 1
- Creatinine increases exceed 30% from baseline 1
- Bilateral renal artery stenosis is suspected 1
- Hyperkalemia develops (>5.5 mmol/L) 1
Management Algorithm
For creatinine/BUN increases <30% 1:
- Continue ARB therapy
- Ensure adequate hydration
- Discontinue NSAIDs if possible 1
- Monitor potassium and creatinine periodically 1
For creatinine increases 30-50% 1:
- Exclude volume depletion
- Stop potassium supplements and potassium-sparing diuretics
- Consider reducing diuretic dose if no congestion present 1
- Recheck chemistry in 1-2 weeks 1
For creatinine increases >50% or >266 μmol/L (3 mg/dL) 1:
- Halve the ARB dose
- Seek specialist consultation if no improvement 1
Critical Clinical Pitfall
The most common error is underdosing or discontinuing ARBs due to fear of creatinine elevation 1. All clinical trials demonstrating efficacy of ARBs in slowing kidney disease progression used maximally tolerated doses—not low doses that provide minimal benefit 1. Even patients with eGFR <30 mL/min/1.73 m² show mortality and CKD progression benefits when ARBs are continued at appropriate doses 1.
The 2018 ACC/AHA guidelines note that a 10-25% increase in serum creatinine may occur in patients with CKD as a result of ARB therapy, and this is considered acceptable 1.
Monitoring Requirements
For patients with eGFR <60 mL/min/1.73 m² receiving ARBs 1:
- Measure serum potassium periodically
- Monitor creatinine and eGFR
- Verify appropriate medication dosing
- Minimize exposure to nephrotoxins
Annual monitoring of both albuminuria and eGFR is essential after initiating ARB therapy to maximum tolerated doses 1.