HMG-CoA reductase inhibitors (statins) and acute kidney injury

A secondary analysis of renal study outcomes

for the RENAL Study Investigators and the ANZICS Clinical Trials Group

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG-CoA reductase inhibitors (statins) with variable findings.

    Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all-cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all-cause mortality at 90 days.

    Results: Of the 1462 participants with the available data on statin usage, 187 (12.8%) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95% confidence interval (CI) = 0.784–1.415, P = 0.730) and day 90 (HR = 1.091, 95% CI = 0.836–1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95% CI = 0.734–1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95% CI = 1.132–2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95% CI = 1.296–3.599, P = 0.003), compared with statin withdrawal.

    Conclusion: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005.

    Original languageEnglish
    Pages (from-to)912-918
    Number of pages7
    JournalNephrology
    Volume24
    Issue number9
    DOIs
    Publication statusPublished - Sep 2019

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    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Acute Kidney Injury
    Outcome Assessment (Health Care)
    Kidney
    Mortality
    Confidence Intervals
    Intensive Care Units
    Propensity Score
    Artificial Respiration

    Cite this

    for the RENAL Study Investigators and the ANZICS Clinical Trials Group. / HMG-CoA reductase inhibitors (statins) and acute kidney injury : A secondary analysis of renal study outcomes. In: Nephrology. 2019 ; Vol. 24, No. 9. pp. 912-918.
    @article{ab1412d74e534a7e871e13fcd4b63292,
    title = "HMG-CoA reductase inhibitors (statins) and acute kidney injury: A secondary analysis of renal study outcomes",
    abstract = "Background: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG-CoA reductase inhibitors (statins) with variable findings. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all-cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all-cause mortality at 90 days. Results: Of the 1462 participants with the available data on statin usage, 187 (12.8{\%}) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95{\%} confidence interval (CI) = 0.784–1.415, P = 0.730) and day 90 (HR = 1.091, 95{\%} CI = 0.836–1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95{\%} CI = 0.734–1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95{\%} CI = 1.132–2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95{\%} CI = 1.296–3.599, P = 0.003), compared with statin withdrawal. Conclusion: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005.",
    keywords = "acute kidney injury, dialysis, HMG-COA reductase inhibitors, mortality, sepsis, statins",
    author = "{for the RENAL Study Investigators and the ANZICS Clinical Trials Group} and Wang, {Amanda Y.} and Konlawij Trongtrakul and Rinaldo Bellomo and Qiang Li and Alan Cass and Martin Gallagher and Wang, {Amanda Y.} and Konlawij Trongtrakul and Rinaldo Bellomo and Qiang Li and Alan Cass and Martin Gallagher",
    year = "2019",
    month = "9",
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    }

    for the RENAL Study Investigators and the ANZICS Clinical Trials Group 2019, 'HMG-CoA reductase inhibitors (statins) and acute kidney injury: A secondary analysis of renal study outcomes', Nephrology, vol. 24, no. 9, pp. 912-918. https://doi.org/10.1111/nep.13597

    HMG-CoA reductase inhibitors (statins) and acute kidney injury : A secondary analysis of renal study outcomes. / for the RENAL Study Investigators and the ANZICS Clinical Trials Group.

    In: Nephrology, Vol. 24, No. 9, 09.2019, p. 912-918.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - HMG-CoA reductase inhibitors (statins) and acute kidney injury

    T2 - A secondary analysis of renal study outcomes

    AU - for the RENAL Study Investigators and the ANZICS Clinical Trials Group

    AU - Wang, Amanda Y.

    AU - Trongtrakul, Konlawij

    AU - Bellomo, Rinaldo

    AU - Li, Qiang

    AU - Cass, Alan

    AU - Gallagher, Martin

    AU - Wang, Amanda Y.

    AU - Trongtrakul, Konlawij

    AU - Bellomo, Rinaldo

    AU - Li, Qiang

    AU - Cass, Alan

    AU - Gallagher, Martin

    PY - 2019/9

    Y1 - 2019/9

    N2 - Background: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG-CoA reductase inhibitors (statins) with variable findings. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all-cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all-cause mortality at 90 days. Results: Of the 1462 participants with the available data on statin usage, 187 (12.8%) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95% confidence interval (CI) = 0.784–1.415, P = 0.730) and day 90 (HR = 1.091, 95% CI = 0.836–1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95% CI = 0.734–1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95% CI = 1.132–2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95% CI = 1.296–3.599, P = 0.003), compared with statin withdrawal. Conclusion: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005.

    AB - Background: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG-CoA reductase inhibitors (statins) with variable findings. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all-cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all-cause mortality at 90 days. Results: Of the 1462 participants with the available data on statin usage, 187 (12.8%) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95% confidence interval (CI) = 0.784–1.415, P = 0.730) and day 90 (HR = 1.091, 95% CI = 0.836–1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95% CI = 0.734–1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95% CI = 1.132–2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95% CI = 1.296–3.599, P = 0.003), compared with statin withdrawal. Conclusion: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005.

    KW - acute kidney injury

    KW - dialysis

    KW - HMG-COA reductase inhibitors

    KW - mortality

    KW - sepsis

    KW - statins

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    U2 - 10.1111/nep.13597

    DO - 10.1111/nep.13597

    M3 - Article

    VL - 24

    SP - 912

    EP - 918

    JO - Nephrology

    JF - Nephrology

    SN - 1320-5358

    IS - 9

    ER -