Diabetic Medications and Post-Operative AKI Risk
Metformin is the primary diabetic medication that increases post-operative AKI risk, but this risk is specifically related to lactic acidosis rather than direct kidney injury, and current evidence suggests metformin should be stopped the evening before surgery and withheld for 48 hours post-operatively in major surgery. 1
Metformin: The Key Concern
Risk Profile and Mechanism
Metformin does not directly cause AKI but poses a risk of lactic acidosis when AKI develops from other causes. 1, 2 The incidence of metformin-associated lactic acidosis is 2-9 per 100,000 patients/year, with mortality rates of 30-50%. 1, 3 In France, analysis showed acute renal failure was present in almost all cases of lactic acidosis, with 20% mortality. 1
Critical Risk Factors for Lactic Acidosis
The following conditions dramatically increase risk when combined with metformin use perioperatively: 1
- Renal impairment (creatinine clearance <60 mL/min)
- Dehydration or fasting (common perioperatively)
- Iodinated contrast administration
- Severe heart failure (LVEF <30%)
- Concomitant nephrotoxic medications (ACE inhibitors, diuretics, NSAIDs)
Evidence-Based Perioperative Management
Stop metformin the evening before surgery for all procedures. 1 This recommendation comes from French anesthesia guidelines recognizing the risk of perioperative volume depletion and renal dysfunction. 1
For major surgery: Do not restart metformin until 48 hours post-operatively AND after confirming adequate renal function. 1
For minor/ambulatory surgery: Metformin can be continued except in cases of severe renal failure. 1
Important Nuance: Metformin May Actually Be Protective
This creates an interesting paradox. Recent high-quality research shows: 4
- In diabetic patients undergoing CABG, preoperative metformin use was associated with REDUCED AKI incidence (IPTW-adjusted p<0.001)
- Protective effects were most significant in patients with eGFR <60 mL/min/1.73 m² and eGFR 60-90 mL/min/1.73 m²
- No increase in lactic acidosis, bleeding, or mortality was observed
A 2020 study of STEMI patients undergoing primary PCI found no difference in CI-AKI between continuous versus discontinued metformin groups (12.6% vs 10.3%, p=0.545), with no cases of lactic acidosis. 5
Other Diabetic Medications
Sulfonylureas and Glinides
Hold on the morning of surgery (both minor and major procedures). 1 These medications cause hypoglycemia risk, not AKI. If taken before emergency surgery with prolonged fasting, glucose infusion should be initiated. 1
Other Non-Insulin Agents
Hold on the morning of minor or major surgery; can be continued for ambulatory surgery. 1 These agents (DPP-4 inhibitors, GLP-1 agonists, SGLT2 inhibitors) do not directly increase AKI risk.
SGLT2 Inhibitors: Addressing the Concern
There was initial concern that SGLT2 inhibitors might promote AKI through volume depletion, particularly when combined with diuretics. However, randomized clinical trials in both advanced kidney disease and high CVD risk populations have NOT found increased AKI risk. 1 Nonsteroidal mineralocorticoid receptor antagonists similarly do not increase AKI risk. 1
Insulin
Never stop basal insulin in Type 1 diabetes due to ketoacidosis risk within hours. 1 Insulin itself does not increase AKI risk and should be continued with appropriate dose adjustments. 1
The Real AKI Risk Factors in Diabetic Surgical Patients
Diabetes itself—not the medications—is the primary risk factor for post-operative AKI. 1 People with diabetes have higher baseline AKI risk than non-diabetics. 1
Diabetes-Related AKI Risk Factors
- Pre-existing diabetic kidney disease (the greatest single risk factor) 1
- Insulin-requiring diabetes (3.92-fold increased AKI risk vs non-diabetics after CABG) 6
- Oral agent-treated diabetes (1.26-fold increased risk) 6
- Concomitant use of ACE inhibitors/ARBs and diuretics (reduce renal blood flow) 1
Perioperative Factors Increasing AKI Risk
- Iodinated contrast exposure (as in cardiac catheterization) 1
- Volume depletion from fasting 1, 2
- Hemodynamic instability 1
- Nephrotoxic medications (NSAIDs, aminoglycosides) 1
Practical Perioperative Algorithm
Pre-Operative Assessment (All Diabetic Patients)
- Measure eGFR and albuminuria to assess baseline kidney function 1
- Screen for diabetic nephropathy (aggravates perioperative AKI risk) 1
- Identify risk factors: age >65, pre-existing CKD, heart failure, planned contrast use 1
Medication Management Protocol
Metformin-specific: 1
- Stop the evening before surgery
- Major surgery: restart after 48h + confirmed adequate renal function
- Minor/ambulatory surgery: can continue unless severe renal failure present
Other oral agents: 1
- Hold morning of surgery
- Continue for ambulatory procedures
Insulin: 1
- Continue basal insulin at usual evening dose
- Never stop in Type 1 diabetes
Intraoperative/Post-Operative Monitoring
- Monitor serum creatinine within 48 hours post-operatively 1
- Maintain adequate hydration (isotonic fluids if NPO and on insulin) 1
- Avoid nephrotoxins (NSAIDs, aminoglycosides) 1
- Target MAP >60 mmHg (>70 mmHg if hypertensive) to maintain renal perfusion 1
Common Pitfalls to Avoid
Do not restart metformin too quickly post-operatively without confirming renal function, especially after major surgery with potential volume shifts or contrast exposure. 1
Do not assume metformin directly causes AKI—the risk is lactic acidosis when AKI develops from other causes (volume depletion, contrast, sepsis). 1, 2
Do not overlook the protective cardiovascular effects of continuing ACE inhibitors/ARBs—small trials show no increased CI-AKI risk from continuing these medications, though they should be held in acute hemodynamic instability. 1
Do not confuse a 30% creatinine rise with ACE inhibitors/ARBs as AKI—this is expected hemodynamic effect and should not prompt discontinuation in the absence of volume depletion. 1
Do not ignore pre-existing diabetic kidney disease—this is the dominant risk factor for post-operative AKI, far exceeding medication effects. 1