In a patient with acute kidney injury (serum creatinine 2.28 mg/dL), which of the following medications should be stopped: gliclazide 60 mg once daily, valsartan 160 mg plus hydrochlorothiazide 12.5 mg once daily, carvedilol 25 mg twice daily, sitagliptin 50 mg plus metformin 1 g once daily, aspirin 80 mg once daily, dapagliflozin 10 mg once daily, atorvastatin 40 mg once daily, and pregabalin 75 mg at bedtime?

Medications to Stop in AKI with Creatinine 2.28 mg/dL

In this patient with acute kidney injury, you must immediately stop metformin, valsartan/HCTZ, and dapagliflozin, while temporarily holding the sitagliptin/metformin combination (stopping the metformin component). These medications pose the highest risk for worsening kidney injury and metabolic complications in the acute setting.

Medications to STOP Immediately

1. Metformin (in Sitagliptin/Metformin combination) - STOP

• Contraindicated with creatinine 2.28 mg/dL 1, 2
• Metformin should be discontinued when eGFR falls below 30 mL/min/1.73 m² 1
• With creatinine of 2.28 mg/dL, the estimated eGFR is likely well below 30 mL/min/1.73 m²
• Risk of lactic acidosis increases significantly in AKI 3
• This is a firm contraindication, not a dose adjustment situation

2. Valsartan/HCTZ - STOP

• Both components must be stopped in AKI 4, 5
• ARBs (valsartan) can worsen AKI by reducing glomerular filtration pressure 6
• Thiazide diuretics (HCTZ) contribute to volume depletion and reduced renal perfusion 5
• The 2023 sick day guidance recommends stopping both ARBs and thiazide diuretics during acute illness with volume depletion 5
• Should be held until volume status is optimized and GFR stabilizes 4

3. Dapagliflozin - STOP

• SGLT2 inhibitors should be temporarily stopped during AKI 7, 5, 8
• The 2023 consensus recommends stopping SGLT2i during acute illness with volume depletion 5
• Risk of euglycemic ketoacidosis, especially in patients on insulin 1, 7
• Should be withheld for at least 3 days before procedures or during acute illness 8
• Can be restarted once volume status is restored and kidney function stabilizes

Medications Requiring Dose Adjustment

4. Sitagliptin (in combination) - REDUCE DOSE

• Reduce to 25 mg once daily 1, 2
• With creatinine 2.28 mg/dL (eGFR likely <30 mL/min/1.73 m²), maximum dose is 25 mg daily 1, 2
• The patient is currently on 50 mg, which exceeds the recommended dose for this level of kidney function
• Continue the DPP-4 inhibitor component for glycemic control while metformin is stopped

5. Gliclazide - USE WITH CAUTION

• Continue but monitor closely for hypoglycemia 1, 2
• Sulfonylureas should be initiated conservatively and titrated slowly in reduced kidney function 1
• Risk of prolonged hypoglycemia increases with declining kidney function
• Consider reducing dose if hypoglycemia occurs, especially with reduced oral intake during illness

6. Pregabalin - REDUCE DOSE

• Requires dose adjustment based on creatinine clearance
• Pregabalin is renally excreted and accumulates in kidney dysfunction
• With creatinine 2.28 mg/dL, dose reduction is necessary to prevent toxicity
• Consult specific dosing guidelines based on calculated creatinine clearance

Medications to CONTINUE

7. Carvedilol - CONTINUE

• Beta-blockers do not require routine discontinuation in AKI
• Important for cardiovascular protection in this diabetic patient
• Monitor blood pressure and heart rate

8. Aspirin - CONTINUE

• Continue for cardiovascular protection 5
• Low-dose aspirin (80 mg) is not typically stopped during AKI
• Benefits for secondary prevention outweigh risks in stable AKI

9. Atorvastatin - CONTINUE

• No dose adjustment needed 9
• Recent evidence suggests statins may actually reduce AKI risk in CKD patients 9
• No renal dose adjustment required
• Continue for cardiovascular protection

Critical Management Points

Volume Status Assessment:

• Evaluate for signs of volume depletion (hypotension, tachycardia, decreased urine output)
• Correct volume depletion before considering restarting any stopped medications 4

When to Restart Medications:

• Metformin: Only restart when eGFR recovers to >30 mL/min/1.73 m² and remains stable 1
• Valsartan/HCTZ: Restart within 24-48 hours of normal eating/drinking and stable kidney function 5
• Dapagliflozin: Restart once volume status optimized and kidney function stabilizing 7, 5

Monitoring Requirements:

• Check creatinine and electrolytes daily until stabilized
• Monitor blood glucose closely after stopping metformin and dapagliflozin
• Watch for hypoglycemia with continued gliclazide use
• Reassess volume status and blood pressure regularly

Common Pitfall to Avoid: Do not restart ACE inhibitors/ARBs or SGLT2 inhibitors too early. Wait until volume status is optimized and creatinine is stable or improving. A transient rise in creatinine up to 30% with ARBs is acceptable in chronic use 10, but this does not apply during acute kidney injury.