Diagnostic Performance of Fas Ligand mRNA Expression for Acute Rejection after Kidney Transplantation: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>The value of Fas ligand (FASL) as a diagnostic immune marker for acute renal rejection is controversial; this meta-analysis aimed to clarify the role of FASL in acute renal rejection.</p><p>Methods</p><p>The relevant literature was included by systematic searching the MEDLINE, EMBASE, and Cochrane Library databases. Accuracy data for acute rejection (AR) and potential confounding variables (the year of publication, area, sample source, quantitative techniques, housekeeping genes, fluorescence staining, sample collection time post-renal transplantation, and clinical classification of AR) were extracted after carefully reviewing the studies. Data were analyzed by Meta-DiSc 1.4, RevMan 5.0, and the Midas module in Stata 11.0 software.</p><p>Results</p><p>Twelve relevant studies involving 496 subjects were included. The overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio, together with the 95% CI were 0.64 (0.57–0.70), 0.90 (0.85–0.93), 5.66 (3.51–9.11), 0.30 (0.16–0.54), and 30.63 (14.67–63.92), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.9389. Fagan’s nomogram showed that the probability of AR episodes in the kidney transplant recipient increased from 15% to 69% when FASL was positive, and was reduced to 4% when FASL was negative. No threshold effect, sensitivity analyses, meta-regression, and subgroup analyses based on the potential variables had a significant statistical change for heterogeneity.</p><p>Conclusions</p><p>Current evidence suggests the diagnostic potential for FASL mRNA detection as a reliable immune marker for AR in renal allograft recipients. Further large, multicenter, prospective studies are needed to validate the power of this test marker in the non-invasive diagnosis of AR after renal transplantation.</p></div

Basic information extracted from the eligible studies.

<p>Basic information extracted from the eligible studies.</p

Diagnostic performance of FasL for AR.

<p>Forest plots of overall sensitivity(A), specificity(B), positive likelihood ratio (LR)(C), negative LR(D), diagnostic odds ratio (OR) (E), and SROC curve (F).</p

SROC plot of FasL, granzyme B and perforin for AR diagnosis.

<p>SROC plot of FasL, granzyme B and perforin for AR diagnosis.</p

Study search flow for meta-analysis.

<p>Study search flow for meta-analysis.</p

SROC plot of FasL test for AR diagnosis in subgroups analyses.

<p>(A), the year of publication; (B), sample; (C), area; (D), PCR technique; (E), housekeeping gene; (F), fluorescence staining; (G), clinical classification of AR.</p

Deeks’ funnel plot for the assessment of potential bias in FasL analysis.

<p>Deeks’ funnel plot for the assessment of potential bias in FasL analysis.</p

The Fagan's nomograms and post-test probability of FasL detection for developing AR.

<p>The Fagan's nomograms and post-test probability of FasL detection for developing AR.</p

Diagnostic accuracy of FasL for AR after kidney transplantation.

<p>Diagnostic accuracy of FasL for AR after kidney transplantation.</p