Vol.:(0123456789) 1 3 Journal of Nephrology https://doi.org/10.1007/s40620-018-00562-2 ORIGINAL ARTICLE Sustained low-efciency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury Paolo Greco 1  · Giuseppe Regolisti 1  · Umberto Maggiore 2  · Elena Ferioli 1  · Filippo Fani 1  · Carlo Locatelli 3  · Elisabetta Parenti 1  · Caterina Maccari 1  · Ilaria Gandolfni 2  · Enrico Fiaccadori 1 Received: 21 August 2018 / Accepted: 14 November 2018 © Italian Society of Nephrology 2018 Abstract Background The choice of the specifc modality and treatment duration of renal replacement therapy (RRT) to adopt in metformin-associated lactic acidosis (MALA) is still debated. We aimed to verify if sustained low-efciency dialysis (SLED) is a rational choice in patients with MALA and acute kidney injury (AKI). Methods We collected serial serum metformin measurements, clinical parameters, and outcome data in ten consecutive patients (mean age 77 years [range 58–88], 5 males) admitted to our renal intensive care unit for suspected MALA associ- ated with AKI and hemodynamic instability. Patients underwent a 16-h SLED session performed with either conventional dialysis machines or machines for continuous RRT (CRRT). A 2-compartment open-infusion pharmacokinetic model with frst-order elimination was ftted to each subject’s serum concentration–time data to model post-SLED rebound and predict the need for further treatments. Results Two patients died within 24 h after SLED start. Three patients needed one further dialysis session. Surviving patients (n = 8) were dialysis-free at discharge. Metformin levels were in the toxic range at baseline (median [range] 32.5 mg/l [13.6–75.6]) and decreased rapidly by the end of SLED (8.1 mg/l [4.5–15.8], p < 0.001 vs. baseline), without diferences according to the dialysis machine used (p = 0.84). We observed a slight 4-h post-SLED rebound (9.7 mg/l [3.5–22.0]), which could be predicted by our pharmacokinetic model. Accordingly, we predicted that the majority of patients would need one additional dialysis session performed the following day to restore safe metformin levels. Conclusions A 16-h SLED session, performed with either conventional dialysis machines or CRRT machines, allows efec- tive metformin removal in patients with MALA and AKI. However, due to possible post-SLED rebound in serum metformin levels, one additional dialysis treatment is required the following day in the majority of patients. Keywords Metformin · Lactic acidosis · Acute kidney injury · Sustained low-efciency dialysis · Pharmacokinetics Introduction Metformin is recommended as first-line treatment in patients with a new diagnosis of type-2 diabetes mellitus (T2DM) [1, 2] as it is efective, inexpensive, has a low risk of hypoglycemia, and may reduce the risk of cardiovas- cular events [3]. A rare but dangerous side efect of met- formin treatment is lactic acidosis (LA), usually observed with inappropriate dose prescriptions in the presence of coexistent risk factors, in particular chronic kidney disease (CKD) [4]. Metformin-associated lactic acidosis (MALA) bears a high mortality risk, especially when diagnosis and/ or treatment are missed or delayed [5]. No specifc antidote is available to reverse the toxic efects of metformin, and Paolo Greco, Giuseppe Regolisti and Umberto Maggiore contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40620-018-00562-2) contains supplementary material, which is available to authorized users. * Giuseppe Regolisti giuregolisti@gmail.com 1 Acute and Chronic Renal Failure Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy 2 Renal Transplant Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy 3 Poison Control Centre and National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifci Maugeri Spa-SB, IRCCS Pavia Hospital and University of Pavia, Pavia, Italy