Evidence map›Paper›PMID 31584924›Full record

ReviewTransplantation2019

Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention.

David K Metz, Nick Holford, Joshua Y Kausman, Amanda Walker, Noel Cranswick, Christine E Staatz, Katherine A Barraclough, Francesco Ierino

Erratum issuedOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.

  1. Pooled it
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  6. Review
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  13. Review
  14. Does Age Influence Immunosuppressant Drug Pharmacokinetics in Kidney Transplant Recipients?European journal of drug metabolism and pharmacokinetics · 2024
    Article
  15. Article
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  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

David K MetzDepartment of Nephrology, Royal Children's Hospital, Melbourne, VIC, Australia.
Nick HolfordDepartment of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand.
Joshua Y KausmanDepartment of Nephrology, Royal Children's Hospital, Melbourne, VIC, Australia.
Amanda WalkerDepartment of Nephrology, Royal Children's Hospital, Melbourne, VIC, Australia.
Noel CranswickDepartment of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia.
Christine E StaatzSchool of Pharmacy, University of Queensland, Brisbane, QLD, Australia.
Katherine A BarracloughDepartment of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia.
Francesco IerinoDepartment of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia.
University of Melbourne · AUMurdoch Children's Research Institute · AUThe Royal Melbourne Hospital · AUUniversity of Auckland · NZUniversity of Queensland · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The immunosuppressive agent mycophenolate is used extensively in kidney transplantation, yet dosing strategy applied varies markedly from fixed dosing ("one-dose-fits-all"), to mycophenolic acid (MPA) trough concentration monitoring, to dose optimization to an MPA exposure target (as area under the concentration-time curve [MPA AUC0-12]). This relates in part to inconsistent results in prospective trials of concentration-controlled dosing (CCD). In this review, the totality of evidence supporting mycophenolate CCD is examined: pharmacological characteristics, observational data linking exposure to efficacy and toxicities, and randomized controlled trials of CCD, with attention to dose optimization method and exposure achieved. Fixed dosing of mycophenolate consistently leads to underexposure associated with rejection, as well as overexposure associated with toxicities. When CCD is driven by pharmacokinetic calculation to a target concentration (target concentration intervention), MPA exposure is successfully controlled and clinical benefits are seen. There remains a need for consensus on practical aspects of mycophenolate target concentration intervention in contemporary tacrolimus-containing regimens and future research to define maintenance phase exposure targets. However, given ongoing consequences of both overimmunosuppression and underimmunosuppression in kidney transplantation, impacting short- and long-term outcomes, these should be a priority. The imprecise "one-dose-fits-all" approach should be replaced by the clinically proven MPA target concentration strategy.

Indexed as

AllograftsArea Under CurveConsensusDose-Response Relationship, DrugEvidence-Based MedicineGraft RejectionHumansImmunosuppression TherapyImmunosuppressive AgentsKidneyKidney TransplantationMycophenolic AcidObservational Studies as TopicTime FactorsImmunosuppressive AgentsMycophenolic Acid

Identifiers

PMID31584924
PMCPMC6756255
OpenAlexW2942232198

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.