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Sustained low-efficiency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury

  • Paolo Greco
  • Giuseppe Regolisti
  • Umberto Maggiore
  • Elena Ferioli
  • Filippo Fani
  • Carlo Locatelli
  • Elisabetta Parenti
  • Caterina Maccari
  • Ilaria Gandolfini
  • Enrico Fiaccadori
Original Article
  • 10 Downloads

Abstract

Background

The choice of the specific 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-efficiency 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 associated 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 first-order elimination was fitted 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 differences 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 effective 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-efficiency dialysis Pharmacokinetics 

Notes

Author contributions

Research idea and study design: PG, GR, UM, EnFi; data acquisition: PG, ElFe, FF, EP, CM, IG; data analysis/interpretation: UM, GR, PG; statistical analysis: UM, GR; supervision and mentorship: EnFi, GR. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study, involving human participants, were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

40620_2018_562_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 KB)
40620_2018_562_MOESM2_ESM.doc (34 kb)
Supplementary material 2 (DOC 34 KB)
40620_2018_562_MOESM3_ESM.doc (29 kb)
Supplementary material 3 (DOC 29 KB)

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Copyright information

© Italian Society of Nephrology 2018

Authors and Affiliations

  • 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 Gandolfini
    • 2
  • Enrico Fiaccadori
    • 1
  1. 1.Acute and Chronic Renal Failure Unit, Department of Medicine and SurgeryUniversity of ParmaParmaItaly
  2. 2.Renal Transplant Unit, Department of Medicine and SurgeryUniversity of ParmaParmaItaly
  3. 3.Poison Control Centre and National Toxicology Information Centre, Toxicology UnitIstituti Clinici Scientifici Maugeri Spa-SB, IRCCS Pavia Hospital and University of PaviaPaviaItaly

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