What to do with the dose of sacubitril/valsartan (arni) if creatinine (cr) increases and urea levels rise, indicating impaired renal function?

Management of ARNI Dose with Rising Creatinine and Urea

Continue sacubitril/valsartan at the current dose and closely monitor renal function, as the creatinine rise from 1.5 to 1.7 mg/dL (13% increase) falls well within acceptable limits and does not require dose reduction.

Assessment of Renal Function Changes

The observed changes in your patient's renal parameters need to be evaluated against established thresholds for RAAS inhibitor management:

• The creatinine increase from 1.5 to 1.7 mg/dL represents approximately a 13% rise, which is well below the 50% threshold that would trigger intervention 1.
• An increase in creatinine up to 50% above baseline, or to 266 μmol/L (3 mg/dL), whichever is smaller, is acceptable when treating with ACE inhibitors, ARBs, or sacubitril/valsartan 1.
• The elevated urea (from 50 to 134) requires attention but some rise in urea and creatinine is expected and acceptable after initiation of RAAS-blocking agents if the increase is small and asymptomatic 1.

Immediate Actions to Take

Before making any dose adjustments to sacubitril/valsartan, systematically address reversible factors:

• Check for and discontinue nephrotoxic medications, particularly NSAIDs, which are common culprits 1, 2.
• Assess volume status: If there are no signs or symptoms of congestion, consider reducing diuretic dose, as overdiuresis can cause prerenal azotemia 1.
• Review other potassium-sparing agents (amiloride, triamterene) and potassium supplements that may be contributing 1.
• Evaluate hydration status, as dehydration is a common reversible cause of creatinine elevation 2.
• Check serum potassium levels to ensure they remain ≤5.5 mmol/L 1.

Monitoring Protocol

Implement close surveillance without stopping therapy:

• Recheck renal function (creatinine, urea, eGFR) and potassium within 1-2 weeks 1, 3.
• Monitor blood chemistry frequently and serially until creatinine and potassium plateau 1.
• Continue sacubitril/valsartan at current dose during this monitoring period unless specific thresholds are crossed 3.

Thresholds for Dose Reduction

Halve the dose of sacubitril/valsartan only if 1:

• Creatinine increases by >100% from baseline, OR
• Creatinine rises to >310 μmol/L (3.5 mg/dL), OR
• eGFR falls to <20 mL/min/1.73 m², OR
• Potassium rises to >5.5 mmol/L

Stop sacubitril/valsartan immediately and seek specialist advice if 1:

• Creatinine rises to ≥310 μmol/L (3.5 mg/dL), OR
• Potassium rises to >6.0 mmol/L, OR
• eGFR deteriorates by >30% during titration 3

Evidence Supporting Continuation

Recent high-quality evidence strongly supports maintaining sacubitril/valsartan despite modest renal function changes:

• In patients experiencing eGFR deterioration to <30 mL/min/1.73 m², continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk compared to discontinuation 4.
• Sacubitril/valsartan has similar effects on kidney function compared to RAS inhibitors alone, with meta-analyses showing it may actually increase eGFR (MD = 1.90,95% CI 0.30-3.50) 5.
• The decline of eGFR with sacubitril/valsartan is slower than with ACEI/ARB alone in patients with chronic kidney disease 6.
• Over 12 months, sacubitril/valsartan has similar effects on kidney function to irbesartan in patients with moderate to severe CKD (eGFR 20-60 mL/min/1.73 m²) 7.

Critical Pitfalls to Avoid

• Do not prematurely discontinue sacubitril/valsartan, as clinical deterioration is likely if treatment is withdrawn, and it is very rarely necessary to stop therapy 1.
• Do not rely solely on absolute creatinine values; calculate the percentage change from baseline and eGFR 2.
• Recognize that a slight increase in serum creatinine (up to 20-30%) when on RAAS inhibitors doesn't necessarily indicate progressive renal deterioration 2.
• The FDA labeling for sacubitril/valsartan emphasizes close monitoring and down-titration rather than immediate discontinuation when renal function declines 8.

Summary Algorithm

1. Current creatinine rise of 13% → No dose change needed
2. Eliminate reversible factors (NSAIDs, volume depletion, excessive diuresis)
3. Recheck labs in 1-2 weeks
4. Continue current dose unless creatinine doubles, exceeds 3.5 mg/dL, or potassium >5.5 mmol/L
5. If thresholds crossed → Halve dose and recheck in 1-2 weeks
6. Seek specialist advice before discontinuation