Which medications should be discontinued in a patient with stage 4 Chronic Kidney Disease (CKD)?

Medications to Discontinue in Stage 4 CKD

In stage 4 CKD (GFR 15-29 mL/min/1.73 m²), you must discontinue metformin, avoid herbal remedies entirely, stop first-generation sulfonylureas, and eliminate NSAIDs unless absolutely necessary with extreme caution. 1

Mandatory Discontinuations

Metformin

• Discontinue metformin when GFR falls below 30 mL/min/1.73 m² (stage 4-5 CKD) due to accumulation risk and potential for lactic acidosis 1
• The FDA black-box warning specifically contraindicates metformin in patients with eGFR <30 mL/min/1.73 m² 2
• While lactic acidosis is rare, toxic metformin accumulation occurs as renal clearance is substantially impaired at this level of kidney function 1, 2

Herbal Remedies

• Stop all herbal remedies completely - KDIGO provides a strong recommendation (1B) against their use in any stage of CKD 1
• These products lack safety data, have unpredictable nephrotoxic potential, and may contain undisclosed ingredients harmful to compromised kidneys 1

First-Generation Sulfonylureas

• Discontinue chlorpropamide, tolazamide, and tolbutamide immediately 1
• These agents and their active metabolites accumulate dangerously in stage 4 CKD, causing prolonged half-lives and severe hypoglycemia risk 1
• The 5-fold increase in severe hypoglycemia episodes in CKD patients with insulin makes this class particularly hazardous 1

High-Risk Medications Requiring Discontinuation or Extreme Caution

NSAIDs

• Discontinue NSAIDs in stage 4 CKD unless pain management alternatives have failed 1, 3
• NSAIDs cause prerenal failure through prostaglandin inhibition, leading to afferent arteriole vasoconstriction and further GFR reduction 3, 4
• Risk of acute kidney injury, electrolyte derangements, hypervolemia, and worsening heart failure/hypertension is substantially elevated at GFR <30 mL/min/1.73 m² 3
• If absolutely necessary, use the lowest effective dose for the shortest duration with close monitoring 3

Nephrotoxic Agents Requiring Review

Aminoglycosides (e.g., gentamicin):

• Should generally be avoided in stage 4 CKD unless no alternative exists 5, 6
• If required, dose adjustment is mandatory with therapeutic drug monitoring of peak (<12 mcg/mL) and trough (<2 mcg/mL) levels 5
• The risk of irreversible ototoxicity and nephrotoxicity increases dramatically with impaired renal function 5, 6

Lithium:

• Requires intensive monitoring of drug levels, eGFR, and electrolytes if continued 1
• Consider alternative mood stabilizers given the narrow therapeutic window and high nephrotoxicity risk 1

Digoxin:

• Dose reduction is essential as renal clearance is impaired 1
• Monitor levels closely due to narrow therapeutic window and increased toxicity risk 1

Medications Requiring Temporary Discontinuation

During Acute Illness or Surgery

Temporarily stop these medications 48-72 hours before elective surgery or during acute illness that increases AKI risk: 1

• ACE inhibitors and ARBs
• Aldosterone antagonists
• Diuretics
• SGLT2 inhibitors
• Metformin (if still on it at higher GFR)

Critical caveat: Document a clear restart plan and communicate it to the patient and all providers, as failure to restart these medications post-procedure causes significant harm 1

Before Contrast Procedures

• Stop metformin (if GFR 30-60) prior to iodinated contrast procedures 2
• Re-evaluate eGFR 48 hours post-procedure before restarting 2
• Withdraw other potentially nephrotoxic agents before and after radiocontrast administration 1

Medications Requiring Dose Adjustment (Not Discontinuation)

Second-Generation Sulfonylureas

• Glipizide is preferred as it lacks active metabolites and doesn't increase hypoglycemia risk in CKD 1
• Glyburide and glimepiride require dose reduction due to active metabolite accumulation 1

Meglitinides

• Repaglinide: Start with low doses at meals, titrate cautiously when GFR <30 mL/min/1.73 m² 1
• Nateglinide: Use 60 mg with meals, titrate cautiously when GFR <30 mL/min/1.73 m² 1

Insulin

• Reduce insulin doses by 25-50% as one-third of insulin degradation occurs in the kidneys, and impaired renal function prolongs insulin half-life 1
• Intensify glucose monitoring to prevent the 5-fold increased risk of severe hypoglycemia 1

Over-the-Counter Medications to Avoid

• All OTC NSAIDs (ibuprofen, naproxen) 1
• Nutritional protein supplements without medical supervision 1
• Magnesium-containing antacids and laxatives (risk of hypermagnesemia) 7
• Phosphate-containing products (risk of hyperphosphatemia) 7

Implementation Strategy

Perform comprehensive medication reconciliation: 1

• Review all prescriptions, OTC medications, supplements, and herbal products
• Assess continued indication for each medication
• Evaluate potential drug-drug interactions
• Check for medications with narrow therapeutic windows requiring level monitoring 1

Establish collaborative care: 1

• Engage clinical pharmacists for medication management
• Coordinate with all prescribing specialists
• Use drug stewardship tools designed for CKD patients 1

Monitor closely: 1

• Check eGFR, electrolytes, and therapeutic drug levels regularly
• Increase monitoring frequency during transitions of care
• Assess for signs of drug toxicity or adverse effects 1