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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)297-306
Number of pages10
JournalJournal of Nephrology
Volume32
Issue number2
DOIs
Publication statusPublished - Apr 12 2019

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Lactic Acidosis
Metformin
Acute Kidney Injury
Dialysis
Renal Replacement Therapy
Pharmacokinetics
Serum
Poisons

Keywords

  • Acute kidney injury
  • Lactic acidosis
  • Metformin
  • Pharmacokinetics
  • Sustained low-efficiency dialysis

ASJC Scopus subject areas

  • Nephrology

Cite this

Sustained low-efficiency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury. / Greco, Paolo; Regolisti, Giuseppe; Maggiore, Umberto; Ferioli, Elena; Fani, Filippo; Locatelli, Carlo; Parenti, Elisabetta; Maccari, Caterina; Gandolfini, Ilaria; Fiaccadori, Enrico.

In: Journal of Nephrology, Vol. 32, No. 2, 12.04.2019, p. 297-306.

Research output: Contribution to journalArticle

Greco, P, Regolisti, G, Maggiore, U, Ferioli, E, Fani, F, Locatelli, C, Parenti, E, Maccari, C, Gandolfini, I & Fiaccadori, E 2019, 'Sustained low-efficiency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury', Journal of Nephrology, vol. 32, no. 2, pp. 297-306. https://doi.org/10.1007/s40620-018-00562-2
Greco, Paolo ; Regolisti, Giuseppe ; Maggiore, Umberto ; Ferioli, Elena ; Fani, Filippo ; Locatelli, Carlo ; Parenti, Elisabetta ; Maccari, Caterina ; Gandolfini, Ilaria ; Fiaccadori, Enrico. / Sustained low-efficiency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury. In: Journal of Nephrology. 2019 ; Vol. 32, No. 2. pp. 297-306.
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AU - Greco, Paolo

AU - Regolisti, Giuseppe

AU - Maggiore, Umberto

AU - Ferioli, Elena

AU - Fani, Filippo

AU - Locatelli, Carlo

AU - Parenti, Elisabetta

AU - Maccari, Caterina

AU - Gandolfini, Ilaria

AU - Fiaccadori, Enrico

PY - 2019/4/12

Y1 - 2019/4/12

N2 - 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.

AB - 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.

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KW - Sustained low-efficiency dialysis

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