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Dose-related effects of metformin on acid–base balance and renal function in patients with diabetes who develop acute renal failure: a cross-sectional study

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Abstract

Aims

The role of metformin in the development of lactic acidosis (LA) in the setting of acute renal failure (ARF) is debated. Moreover, recent experiments suggested that metformin can also be nephrotoxic, but little clinical data exist about this topic. We sought to investigate these possible associations in a large cohort of patients with diabetes who developed ARF.

Methods

We analyzed data from patients with diabetes admitted to our emergency department between 2007 and 2011 with ARF and a previously normal renal function (n = 126). We compared acid–base balance and renal function of patients taking metformin (n = 74) with patients not taking it (n = 52).

Results

Patients taking metformin had decreased pH (7.31 ± 0.16 vs 7.39 ± 0.11, p = 0.008) and higher lactates (4.54 ± 4.30 vs 1.71 ± 1.14 mmol/L, p < 0.001). Both acidosis (pH < 7.35) and LA (lactates >5 mmol/L and pH < 7.35) were more frequently observed in this group (p = 0.0491 and p < 0.001, respectively). Multivariate analysis ruled out the role of some possible confounders, especially decreased renal function. The influence of metformin on pH and lactates grew significantly with higher doses of the drug (p = 0.259 and p = 0.092 for <1 g/day, p = 0.289 and p < 0.001 for 1–2 g/day, p = 0.009 and p < 0.001 for 2–3 g/day, for pH and lactates, respectively). Metformin influenced creatinine levels in a dose-related manner as well (p = 0.925 for <1 g/day, p = 0.033 for 1–2 g/day, p < 0.001 for 2–3 g/day).

Conclusions

In patients with diabetes who were admitted to our emergency department with ARF, the use of metformin was associated in a dose-related fashion with both LA and worse renal function.

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Authors and Affiliations

  1. Nephrology and Dialysis Unit, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, MI, Italy

    David Cucchiari, Manuel Alfredo Podestà, Elisa Merizzoli, Albania Calvetta, Emanuela Morenghi, Claudio Angelini, Claudio Ponticelli & Salvatore Badalamenti

Authors
  1. David Cucchiari
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  2. Manuel Alfredo Podestà
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  3. Elisa Merizzoli
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  4. Albania Calvetta
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  5. Emanuela Morenghi
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  6. Claudio Angelini
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  7. Claudio Ponticelli
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  8. Salvatore Badalamenti
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Correspondence to David Cucchiari.

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The authors declare that they have no conflict of interest.

Ethical standard

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Human and animal rights

The authors have followed the rules of good clinical and scientific practice.

Informed consent

The local ethics committee approved the study and waived informed consent as data were collected retrospectively on an anonymized database.

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Managed by Massimo Porta.

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Cucchiari, D., Podestà, M.A., Merizzoli, E. et al. Dose-related effects of metformin on acid–base balance and renal function in patients with diabetes who develop acute renal failure: a cross-sectional study. Acta Diabetol 53, 551–558 (2016). https://doi.org/10.1007/s00592-016-0836-2

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  • DOI: https://doi.org/10.1007/s00592-016-0836-2

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