Regional citrate anticoagulation ensures safe and effective kidney replacement therapy in metformin-associated lactic acidosis.

Abstract

Background: Metformin-associated lactic acidosis (MALA) is a rare but potentially life-threatening complication of metformin therapy, often associated with acute kidney injury (AKI). Sustained low-efficiency dialysis (SLED) offers both haemodynamic stability and effective metformin clearance. However, during regional citrate anticoagulation (RCA), concerns may arise regarding citrate accumulation due to metformin-induced impairment of cellular metabolism. This study assesses the efficacy and safety of SLED with RCA in the management of MALA, providing direct measurements of serum metformin and citrate levels to evaluate drug clearance and potential citrate accumulation.

Methods: A prospective observational study was conducted on consecutive critically ill patients with severe AKI and suspected MALA undergoing a 16-h SLED session with RCA. Demographic, clinical and laboratory data were collected. Serum metformin and citrate levels were measured via high-performance liquid chromatography and enzymatic spectrophotometric analysis, respectively. Mixed effects linear models were used to analyse serum metformin, lactate, citrate, electrolytes and acid-base parameters over time.

Results: Twenty-three patients (median age 79 years; APACHE II score 29) had metformin levels at intensive care unit (ICU) admission above the therapeutic range (median 29.1 mg/l; normal: 0.5-3). ICU mortality was 22% (n = 5). SLED led to significant haemodynamic and acid-base improvements, with a marked reduction in serum lactate. Metformin levels decreased from 27.75 mg/l at SLED start to 3.95 mg/l, with minimal rebound. Four SLED sessions (17%) were interrupted, with one being due to impending circuit clotting. No biochemical or clinical signs of citrate accumulation were observed, with serum citrate levels consistently <0.5 mmol/l. No significant correlation was found between serum metformin and citrate levels or between lactate and citrate.

Conclusions: SLED with RCA is safe and effective in patients with MALA, ensuring adequate KRT duration, rapid metformin clearance and acid-base status restoration. Direct citrate measurements confirmed the absence of accumulation, reinforcing RCA as a viable anticoagulation strategy in this clinical setting.