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Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

Overview of attention for article published in Cochrane database of systematic reviews, July 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (51st percentile)

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1 blog
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13 tweeters
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1 Facebook page

Citations

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63 Dimensions

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124 Mendeley
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Title
Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients
Published in
Cochrane database of systematic reviews, July 2017
DOI 10.1002/14651858.cd006750.pub2
Pubmed ID
Authors

Krishna M Karpe, Girish S Talaulikar, Giles D Walters

Abstract

Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death. We searched the Cochrane Kidney and Transplant Specialised Register to 11 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs) where drug regimens containing CNI were compared to alternative drug regimens (CNI withdrawal, tapering or low dose) in the post-transplant period were included, without age or dosage restriction. Two authors independently assessed studies for eligibility, risk of bias, and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). We included 83 studies that involved 16,156 participants. Most were open-label studies; less than 30% of studies reported randomisation method and allocation concealment. Studies were analysed as intent-to-treat in 60% and all pre-specified outcomes were reported in 54 studies. The attrition and reporting bias were unclear in the remainder of the studies as factors used to judge bias were reported inconsistently. We also noted that 50% (47 studies) of studies were funded by the pharmaceutical industry.We classified studies into four groups: CNI withdrawal or avoidance with or without substitution with mammalian target of rapamycin inhibitors (mTOR-I); and low dose CNI with or without mTOR-I. The withdrawal groups were further stratified as avoidance and withdrawal subgroups for major outcomes.CNI withdrawal may lead to rejection (RR 2.54, 95% CI 1.56 to 4.12; moderate certainty evidence), may make little or no difference to death (RR 1.09, 95% CI 0.96 to 1.24; moderate certainty), and probably slightly reduces graft loss (RR 0.85, 95% CI 0.74 to 0.98; low quality evidence). Hypertension was probably reduced in the CNI withdrawal group (RR 0.82, 95% CI 0.71 to 0.95; low certainty), while CNI withdrawal may make little or no difference to malignancy (RR 1.10, 95% CI 0.93 to 1.30; low certainty), and probably makes little or no difference to cytomegalovirus (CMV) (RR 0.87, 95% CI 0.52 to 1.45; low certainty)CNI avoidance may result in increased acute rejection (RR 2.16, 95% CI 0.85 to 5.49; low certainty) but little or no difference in graft loss (RR 0.96, 95% CI 0.79 to 1.16; low certainty). Late CNI withdrawal increased acute rejection (RR 3.21, 95% CI 1.59 to 6.48; moderate certainty) but probably reduced graft loss (RR 0.84, 95% CI 0.72 to 0.97, low certainty).Results were similar when CNI avoidance or withdrawal was combined with the introduction of mTOR-I; acute rejection was probably increased (RR 1.43; 95% CI 1.15 to 1.78; moderate certainty) and there was probably little or no difference in death (RR 0.96; 95% CI 0.69 to 1.36, moderate certainty). mTOR-I substitution may make little or no difference to graft loss (RR 0.94, 95% CI 0.75 to 1.19; low certainty), probably makes little of no difference to hypertension (RR 0.86, 95% CI 0.64 to 1.15; moderate), and probably reduced the risk of cytomegalovirus (CMV) (RR 0.60, 95% CI 0.44 to 0.82; moderate certainty) and malignancy (RR 0.69, 95% CI 0.47 to 1.00; low certainty). Lymphoceles were increased with mTOR-I substitution (RR 1.45, 95% CI 0.95 to 2.21; low certainty).Low dose CNI combined with mTOR-I probably increased glomerular filtration rate (GFR) (MD 6.24 mL/min, 95% CI 3.28 to 9.119; moderate certainty), reduced graft loss (RR 0.75, 95% CI 0.55 to 1.02; moderate certainty), and made little or no difference to acute rejection (RR 1.13 ; 95% CI 0.91 to 1.40; moderate certainty). Hypertension was decreased (RR 0.98, 95% CI 0.80 to 1.20; low certainty) as was CMV (RR 0.41, 95% CI 0.16 to 1.06; low certainty). Low dose CNI plus mTOR-I makes probably makes little of no difference to malignancy (RR 1.22, 95% CI 0.42 to 3.53; low certainty) and may make little of no difference to death (RR 1.16, 95% CI 0.71 to 1.90; moderate certainty). CNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.

Twitter Demographics

The data shown below were collected from the profiles of 13 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 124 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 124 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 34 27%
Student > Bachelor 14 11%
Researcher 14 11%
Student > Ph. D. Student 11 9%
Student > Postgraduate 7 6%
Other 22 18%
Unknown 22 18%
Readers by discipline Count As %
Medicine and Dentistry 50 40%
Nursing and Health Professions 14 11%
Pharmacology, Toxicology and Pharmaceutical Science 7 6%
Biochemistry, Genetics and Molecular Biology 5 4%
Agricultural and Biological Sciences 3 2%
Other 19 15%
Unknown 26 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 September 2018.
All research outputs
#1,407,446
of 15,690,347 outputs
Outputs from Cochrane database of systematic reviews
#3,714
of 11,257 outputs
Outputs of similar age
#37,795
of 270,237 outputs
Outputs of similar age from Cochrane database of systematic reviews
#127
of 262 outputs
Altmetric has tracked 15,690,347 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,257 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.3. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 270,237 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 262 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.