Transplant Trial Watch

Down-regulation of inflammatory signaling pathways despite up-regulation of Toll-like receptors; the effects of corticosteroid therapy in brain-dead kidney donors, a double-blind, randomized, controlled trial.

Jafari R, Aflatoonian R, et al.

Molecular immunology 2017; 94: 36-44.


Aims
To determine the effects of methylprednisolone (MPN) on pattern recognition receptors and their associated signalling pathway molecules in brain-dead (BD) kidney donors.

Interventions
BD donors were randomised to one of three groups and received either normal donation (control group), or common MPN therapy at 15 mg/kg/d (T1 group), or MPN at 15 mg/kg/d after consent for kidney donation and an additional 100 mg/2 h until organ harvesting (T2 group).

Participants
51 BD kidney donors aged 18–60 years.

Outcomes
Measured outcomes included Toll-like receptors (TLRs) 1-9 and their signalling pathway molecules, inflammatory cytokines and creatinine and cystatin C serum levels.

Follow-up
12 months

CET Conclusions
This was primarily a biochemical study of serum samples from brain dead donors prior to organ retrieval. The paper describes the different panel of Toll-like receptors and downstream molecules variably expressed in the two treatment arms compared to the control group. There are over 20 molecules assessed and so it becomes a little difficult to assess the significance of the picture presented as a whole. The first treatment group had increased levels of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha. As these levels were lower in the second treatment arm (which received more methylprednisolone) the authors have concluded that treatment with non-standard methylprednisolone reduces inflammation close to the level seen in live donors, but standard treatment increases the immunogenicity of organs prior to retrieval. In the clinical results the serum creatinine of recipients is presented to 6 months after transplant, showing a significantly higher creatinine in those whose donor received 15mg/kg/day of methylprednisolone, but similar levels between kidneys from live donors and brain dead donors who received additional methylprednisolone 100mg/2 hours. The method of randomisation and allocation concealment (or blinding) was not described so we cannot be sure that these standards were met. There is no flowsheet showing excluded numbers of donors, nor a description of these. The overall quality score is therefore low.

Jadad score
1

Data analysis
Per protocol analysis

Allocation concealment
No

Trial registration
Iranian Registry of Clinical Trials - IRCT2015071323192N1

Funding source
Non-industry funded