Metformin and contrast induced nephropathy

• Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality (1)
  • chronic kidney disease is the primary predisposing factor for CIN (estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk)
  • nephropathy induced by contrast medium is defined as an impairment in renal function that occurs within 72 hours of giving contrast medium (2)
    • characterised by an increase in serum creatinine of at least 44 µmol/litre (or 25% above the baseline)
      • the peak in creatinine level is typically three to five days after administration of contrast medium - the creatinine level returns to baseline values within two weeks
      • CIN accounts for about 12% of all cases of hospital acquired renal failure
        • risk factors for CIN include:
          • pre-existing renal insufficiency
          • diabetes mellitus
          • age > 75 years
          • concurrent use of nephrotoxic drugs (non-steroidal anti-inflammatory drugs, biguanides, aminoglycosides)
          • dehydration
          • hypertension
          • hypotension
          • heart failure
          • cirrhosis
          • nephrotic syndrome
        • modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration
          • cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion
          • in patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal
    • NICE state:
      • before offering iodine-based contrast media to adults, assess their risk of acute kidney injury but do not delay emergency imaging. Be aware that increased risk is associated with:
        • chronic kidney disease (adults with an eGFR less than 40 ml/min/1.73 m2 are at particular risk)
        • diabetes but only with chronic kidney disease (adults with an eGFR less than 40 ml/min/1.73 m2 are at particular risk)
        • heart failure
        • renal transplant
        • age 75 years or over
        • hypovolaemia
        • increasing volume of contrast agent
        • intra-arterial administration of contrast medium with first-pass renal exposure (when the contrast medium reaches the renal arteries in a relatively undiluted form, for example, through injection into the left heart, thoracic and suprarenal abdominal aorta, or the renal arteries)
      • for adults needing non-emergency imaging who are assessed as being at increased risk of kidney injury, investigate for chronic kidney disease before offering iodine-based contrast media: measure eGFR or check an eGFR result obtained within the past 3 months
        
        
• with respect to metformin:
  • acute renal failure is a well known complication of procedures that involve iodinated contrast media in diabetic patients
    • type 2 diabetic patients are often treated with the biguanide metformin, which is excreted by the kidney
      • metformin may be withheld for 48 hours from the time of the radiological study if intravenous iodinated contrast media is to be given, with close monitoring of renal function before restarting
        • this is to prevent, in the context of CIN, high serum metformin concentrations, which could lead to lactic acidosis (2)
          • 8% of cases of metformin induced lactic acidosis occur in presence of contrast induced nephropathy (3)
            • risk increases in diabetic patients with preexisting renal impairment
          • nearly 4% of patients with diabetes mellitus and normal renal function may develop CIN (4)
    • The Royal College of Radiologists state (5)
      • Metformin is not nephrotoxic but is exclusively excreted via the kidneys
        • patients on metformin who develop acute kidney injury (AKI) are at risk of developing lactic acidosis
        • advice from the Royal College of Radiologists is that there is no need to stop metformin after receiving contrast if the serum creatinine is within the normal range and/or eGFR > 60 ml/min/1.73m2
        • if serum creatinine is above the normal reference range or eGFR is < 60 ml/min/1.73m2, any decision to stop it for 48 hours should be made in consultation with the referring clinician

Reference:

1. Schweiger MJ et al.Prevention of contrast induced nephropathy: recommendations for the high risk patient undergoing cardiovascular procedures. Catheter Cardiovasc Interv. 2007 Jan;69(1):135-40.
2. Mathew R et al. Acute renal failure induced by contrast medium: steps towards prevention. BMJ 2006:333: 539-40
3. Thomsen HS, Morcos SK. Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines. Br J Radiol 2003:76: 513-8.
4. Parra D et al. Metformin monitoring and change in serum creatinine levels in patients undergoing radiologic procedures involving administration of intravenous contrast media. Pharmacotherapy. 2004 Aug;24(8):987-93. Erratum in: Pharmacotherapy. 2004 Oct;24(10):1489.
5. Faculty of the Royal College of Radiologists. Standards for intravascular contrast administration to adult patients (Accessed 30/12/2019).
6. NICE (September 2023). Acute kidney injury - Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy