Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study.
O'Connell PJ, Zhang W, et al.Lancet 2016; 388(10048): 983-993.
Aims
To develop a predictive gene set that is able to identify renal allografts at risk of progressive injury to prevent the development of interstitial fibrosis and tubular atrophy.
Interventions
Protocol biopsies were collected at 3 months after transplantation. Microarray analysis was done on the first 159 biopsies (discovery set), and the remaining 45 biopsies were used for validation.
Participants
204 adult kidney transplant recipients aged ≥ 18 years.
Outcomes
The primary measured outcomes were fibrosis and allograft loss. Secondary measured outcomes included donor age, recipient race and sex, donor vital status, expanded-criteria donor status, cold ischaemia time, induction therapy, presence of human leucocyte antigen (HLA) antibodies, eGFR at 3 months post-transplantation, acute cellular rejection at or before 3 months, delayed graft function, HLA mismatch, and CADI-3 score.
Follow-up
12 months
CET Conclusions
This is an excellent study in which the authors have identified a set of 13 genes that independently predicted the development of fibrosis at one year after renal transplantation. The genes set had a high predictive capacity and the gene set was superior to that predicted by clinical and pathological variables. This study very impressively shows that the set of 13 genes that the authors have identified could be used to identify kidney transplant recipients at risk of allograft loss before the development of irreversible damage and, in theory, would allow therapy to be modified to prevent progression to fibrosis. Many of the same authors have also shown that biopsies at three months after transplantation with indications of early fibrosis are associated with poorer graft outcome (Nankivell et al., NEJM 2003; 349:2326) and hence the importance of this particular study which might allow those patients to be identified before fibrosis actually develops.
Quality notes
Quality assessment not appropriate
Trial registration
ClinicalTrials.gov - NCT00611702