Are patients with mild to moderate renal impairment on metformin or other oral anti-hyperglycaemic agents at increased risk of contrast-induced nephropathy and metabolic acidosis after radiocontrast exposure?
Introduction
As the frequency of imaging studies using radiocontrast agents has increased, the frequency of radiocontrast agent use has increased in patients with type 2 diabetes. There is controversy as to whether patients taking metformin should discontinue use of metformin during the use of radiocontrast agents because of concerns about metformin-induced lactic acidosis.1, 2, 3, 4 Although metformin itself is not a nephrotoxic drug, and therefore, does not directly induce lactic acidosis, radiocontrast agents are nephrotoxic and can cause lactic acidosis in patients who develop contrast-induced nephropathy (CIN)5; however, lactic acidosis does not occur in all patients with CIN, and the causal relationship between metformin accumulation and lactic acidosis is unclear.6 There is no clinical evidence suggesting that metformin should be discontinued in patients with normal renal function, especially in patients who undergo single computed tomography (CT) with minimal use of radiocontrast agents.3 Furthermore, the most recent guideline from the Royal College of Radiologists advises that there is no need to stop metformin after use of radiocontrast agents in patients with a serum creatinine level within the normal reference range and/or an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2.7 The American College of Radiology advises that it is not necessary to discontinue the use of metformin during CT with radiocontrast agents, and re-evaluation of renal function is not necessary after the use of radiocontrast agents in patients with an eGFR >30 ml/min/1.73m2.8 The Canadian Association of Radiologists Consensus recommends that metformin should be stopped at the time of radiocontrast injection if the patient's eGFR is <45 ml/min/1.73 m2.9 The Contrast Media Safety Committee of the European Society of Urogenital Radiology also has updated its guidelines about the use of metformin when radiocontrast is given. They recommend discontinuing metformin from the time of contrast medium administration if the eGFR is <30 ml/min/1.73 m2.10 The Royal Australian and New Zealand College of Radiologists also recommends that patients receiving intravenous iodinated contrast media with an eGFR ≥30 ml/min/1.73 m2 should continue taking metformin.11 Although these guidelines vary in their method of evaluating renal function, the timing of the discontinuation of metformin, and the timing of the re-evaluation of renal function after the use of radiocontrast agents, most agree that there is no need to discontinue metformin in patients with an eGFR ≥30–45 ml/min/1.73 m2; however, due to a lack of relevant clinical studies, these guidelines reflect expert opinions or case studies.7, 8, 9, 10, 11 The present study investigated whether the use of metformin during CT with radiocontrast agents increases the risk of CIN and lactic acidosis after CT; however, the lactate concentration is often not measured, so metabolic acidosis was used instead of lactic acidosis. The presence of metabolic acidosis was assessed using serum total CO2 levels. Serum bicarbonate comprises about 95% of the total CO2 content; thus, CO2 is a convenient and informative estimate of serum bicarbonate.12
Section snippets
Materials and methods
The records of patients who visited the emergency room and underwent a single CT examination from January 2015 to December 2017 were reviewed. All patient charts were reviewed by the same impartial physician. A total of 461 type 2 diabetic patients with an eGFR between 30 and 59 ml/min/1.73 m2 underwent CT using iodinated contrast medium. In total, 87 patients were excluded for the following reasons: 51 died immediately after admission because of an underlying disease, five received repeat CT
Baseline characteristics
Table 1 summarises clinical characteristics of the enrolled patients. Significant differences were observed between the metformin group and the other OHAs group in incidence of underlying diseases (cerebrovascular diseases), baseline albumin level, baseline eGFR, and baseline creatinine levels (Table 1). Patients who used metformin had a lower prevalence of cerebrovascular disease than did patients taking other OHAs (Table 1). Furthermore, the baseline eGFR and serum albumin levels were higher
Discussion
The present results show that metabolic acidosis after radiocontrast agent administration in patients with reduced renal function (eGFR between 59 and 30 ml/min/1.73 m2) was not associated with metformin use. Metformin has been recommended as the first-choice drug in patients with type 2 diabetes due to its blood glucose-lowering effect, long-term safety, low hypoglycaemic risk, and low risk of weight gain.14, 15, 16 Metformin has been prohibited in patients with renal dysfunction because
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
This study was supported by a grant from the Institute of Health Sciences (IHS GNU-2016-03) and Biomedical Research Institute Fund (GNUHBRIF-2017-0004).
References (27)
- et al.
Canadian Association of Radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012
Can Assoc Radiol J
(2014) - et al.
Contrast-induced nephropathy: definition, epidemiology, and patients at risk
Kidney Int
(2006) - et al.
Clinical risk associated with contrast angiography in metformin treated patients: a clinical review
Clin Radiol
(1998) - et al.
Contraindications to the use of metformin
BMJ
(2003) - et al.
Incidence of lactic acidosis in metformin users
Diabetes Care
(1999) - et al.
Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin
Radiology
(2010) - et al.
Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis
Diabetes Care
(2008) - et al.
Lactic acidosis in patients with diabetes treated with metformin
N Engl J Med
(1998) - et al.
Role of metformin accumulation in metformin-associated lactic acidosis
Diabetes Care
(1995) Standards for intravascular contrast administration to adult patients
Manual on contrast media, version 10. ACR committee on drugs and contrast media
Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients: recommendations for updated ESUR Contrast Medium Safety Committee guidelines
Eur Radiol
Iodinated contrast media guideline
Cited by (3)
Metformin Can Be Safely Used in Patients Exposed to Contrast Media: A Systematic Review and Meta-Analysis
2022, Cardiology (Switzerland)