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Metformin and contrast induced nephropathy

Authoring team

  • 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:
        • encourage oral hydration before and after procedures using intravenous iodine-based contrast media in adults at increased risk of contrast-associated acute kidney injury (see the recommendation on increased risk in the section on assessing risk factors in adults having iodine-based contrast media)
        • for inpatients having iodine-based contrast media, consider intravenous volume expansion with either isotonic sodium bicarbonate or 0.9% sodium chloride if they are at particularly high risk, for example, if:
          • they have an eGFR less than 30 ml/min/1.73 m2
          • they have had a renal transplant
          • a large volume of contrast medium is being used (for example, higher than the standard diagnostic dose or repeat administration within 24 hours)
          • intra-arterial administration of contrast medium with first-pass renal exposure is being used
        • consider temporarily stopping ACE inhibitors and ARBs in adults having iodine-based contrast media if they have chronic kidney disease with an eGFR less than 30 ml/min/1.73 m2
        • be aware that there is a small but increased risk of acute kidney injury associated with an eGFR less than 30 ml/min/1.73 m2
        • do not delay the use of iodine-based contrast media in an emergency if the risk of delaying the contrast media is likely to be clinically significant
      • with respect to outpatient, non-urgent inpatient and community settings
        • before requesting a non-urgent iodine-based contrast media CT scan, assess whether the person has pre-existing kidney disease
        • If available, use an eGFR measurement from the past 6 months to support decision making about the use of iodine-based contrast media. If the person has been acutely unwell or clinically unstable since their last eGFR test, consider using a more recent eGFR
        • if no eGFR is available from the past 6 months, ask the person, or their family members and carers if appropriate, the following screening questions:
          • do they have kidney disease or a kidney transplant?
          • have they seen or are waiting to see a kidney specialist, or a kidney surgeon or urologist?
          • do they have symptoms of acute illness likely to cause acute kidney injury such as diarrhoea, vomiting, fever, hypovolaemia, infection or difficulty passing urine?
        • if the screening questions indicate a history of kidney disease or acute illness to suggest that acute kidney injury is likely, consider an eGFR test to support decision making
        • if the screening questions do not indicate a history of kidney disease and the person is clinically stable, consider proceeding with iodine-based contrast media CT scan without the need for further blood tests before the scan

  • 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 (November 2024). Acute kidney injury - Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy

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