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?

Highlights

• Metformin use was not related with contrast-induced nephropathy in type 2 diabetic patients.

• Metformin use was not related to metabolic acidosis after radiocontrast agent use in type 2 diabetic patients.

• Low serum albumin level, and low serum total CO2 level were associated with metabolic acidosis after radiocontrast agent use.

AIM

To investigate whether the use of metformin during computed tomography (CT) with radiocontrast agents increases the risk of contrast-induced nephropathy (CIN) and metabolic acidosis after CT in type 2 diabetes patients with mild to moderate renal failure.

MATERIALS AND METHODS

Patient records from January 2015 to December 2017 were reviewed retrospectively. A total of 374 patients were included in the final analysis. Of them, 157 patients received metformin, and 217 patients were taking other oral hypoglycaemic agents (OHAs) during radiocontrast administration.

RESULTS

No significant difference in CIN incidence was observed between the metformin use group and the other OHAs group (p=0.085). Metabolic acidosis after CT was seen in 91 (58%) patients who used metformin and 141 (65%) patients who were taking other OHAs. There was no relationship between metabolic acidosis after CT and the use of metformin (p=0.195). Metabolic acidosis after radiocontrast agent exposure was associated with malignant disease, low serum albumin level, and low serum total CO₂ level at baseline.

CONCLUSION

These data show that other factors, but not metformin use, are associated with metabolic acidosis after radiocontrast agent exposure in patients with reduced renal function. These data support current recommendations that there is no need to discontinue metformin before CT using radiocontrast agents in patients with mild to moderate renal failure.

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