Interventions for lowering plasma homocysteine levels in kidney transplant recipients

Amy Kang, Sagar Nigwekar, Vlado Perkovic, Satyarth Kulshrestha, Sophia Zoungas, Sankar Navaneethan, Alan Cass, Martin Gallagher, Giovanni Strippoli, Meg Jardine

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy.

    Objectives: To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants.

    Search methods: We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

    Selection criteria: Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy.

    Data collection and analysis: Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Data was to be pooled using the random effects model.

    Main results: The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 μmol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality.

    Authors' conclusions: There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.
    Original languageEnglish
    Article numberCD007910
    Pages (from-to)1-30
    Number of pages30
    JournalCochrane Database of Systematic Reviews
    Volume2015
    Issue number5
    DOIs
    Publication statusPublished - 4 May 2015

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    Homocysteine
    Kidney
    Confidence Intervals
    Odds Ratio
    Transplant Recipients
    Transplants
    Therapeutics
    Chronic Kidney Failure
    Mortality
    Cardiovascular Diseases
    Renal Replacement Therapy
    Folic Acid
    Patient Selection
    Population
    Randomized Controlled Trials

    Cite this

    Kang, A., Nigwekar, S., Perkovic, V., Kulshrestha, S., Zoungas, S., Navaneethan, S., ... Jardine, M. (2015). Interventions for lowering plasma homocysteine levels in kidney transplant recipients. Cochrane Database of Systematic Reviews, 2015(5), 1-30. [CD007910]. https://doi.org/10.1002/14651858.CD007910.pub2
    Kang, Amy ; Nigwekar, Sagar ; Perkovic, Vlado ; Kulshrestha, Satyarth ; Zoungas, Sophia ; Navaneethan, Sankar ; Cass, Alan ; Gallagher, Martin ; Strippoli, Giovanni ; Jardine, Meg. / Interventions for lowering plasma homocysteine levels in kidney transplant recipients. In: Cochrane Database of Systematic Reviews. 2015 ; Vol. 2015, No. 5. pp. 1-30.
    @article{775d61a42615432885925655824c4593,
    title = "Interventions for lowering plasma homocysteine levels in kidney transplant recipients",
    abstract = "Background: Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy.Objectives: To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants.Search methods: We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.Selection criteria: Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy.Data collection and analysis: Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95{\%} confidence intervals (CI). Data was to be pooled using the random effects model.Main results: The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 μmol/L, 95{\%} CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95{\%} CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95{\%} CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95{\%} CI 0.77 to 1.35), stroke (RR 1.08, 95{\%} CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95{\%} CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95{\%} CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95{\%} CI 0.85 to 1.15). The study was of high quality.Authors' conclusions: There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.",
    author = "Amy Kang and Sagar Nigwekar and Vlado Perkovic and Satyarth Kulshrestha and Sophia Zoungas and Sankar Navaneethan and Alan Cass and Martin Gallagher and Giovanni Strippoli and Meg Jardine",
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    Kang, A, Nigwekar, S, Perkovic, V, Kulshrestha, S, Zoungas, S, Navaneethan, S, Cass, A, Gallagher, M, Strippoli, G & Jardine, M 2015, 'Interventions for lowering plasma homocysteine levels in kidney transplant recipients', Cochrane Database of Systematic Reviews, vol. 2015, no. 5, CD007910, pp. 1-30. https://doi.org/10.1002/14651858.CD007910.pub2

    Interventions for lowering plasma homocysteine levels in kidney transplant recipients. / Kang, Amy; Nigwekar, Sagar; Perkovic, Vlado; Kulshrestha, Satyarth; Zoungas, Sophia; Navaneethan, Sankar; Cass, Alan; Gallagher, Martin; Strippoli, Giovanni; Jardine, Meg.

    In: Cochrane Database of Systematic Reviews, Vol. 2015, No. 5, CD007910, 04.05.2015, p. 1-30.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Interventions for lowering plasma homocysteine levels in kidney transplant recipients

    AU - Kang, Amy

    AU - Nigwekar, Sagar

    AU - Perkovic, Vlado

    AU - Kulshrestha, Satyarth

    AU - Zoungas, Sophia

    AU - Navaneethan, Sankar

    AU - Cass, Alan

    AU - Gallagher, Martin

    AU - Strippoli, Giovanni

    AU - Jardine, Meg

    PY - 2015/5/4

    Y1 - 2015/5/4

    N2 - Background: Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy.Objectives: To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants.Search methods: We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.Selection criteria: Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy.Data collection and analysis: Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Data was to be pooled using the random effects model.Main results: The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 μmol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality.Authors' conclusions: There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.

    AB - Background: Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy.Objectives: To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants.Search methods: We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.Selection criteria: Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy.Data collection and analysis: Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Data was to be pooled using the random effects model.Main results: The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 μmol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality.Authors' conclusions: There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.

    U2 - 10.1002/14651858.CD007910.pub2

    DO - 10.1002/14651858.CD007910.pub2

    M3 - Article

    VL - 2015

    SP - 1

    EP - 30

    JO - Cochrane database of systematic reviews (Online)

    JF - Cochrane database of systematic reviews (Online)

    SN - 1469-493X

    IS - 5

    M1 - CD007910

    ER -

    Kang A, Nigwekar S, Perkovic V, Kulshrestha S, Zoungas S, Navaneethan S et al. Interventions for lowering plasma homocysteine levels in kidney transplant recipients. Cochrane Database of Systematic Reviews. 2015 May 4;2015(5):1-30. CD007910. https://doi.org/10.1002/14651858.CD007910.pub2