title: A Meta-analysis of the Significance of Granzyme B and Perforin in Noninvasive Diagnosis of Acute Rejection After Kidney Transplantation.
abstract: BACKGROUND
  Previous studies have reported that granzyme B (GZMB) and perforin (PRF) could serve as noninvasive biomarkers in the diagnosis of acute rejection (AR) after kidney transplant. Yet, their noninvasive diagnostic value in clinical practice is still unknown.
  
  
  METHODS
  To assess the noninvasive diagnostic performance of GZMB and PRF for AR, we performed a systematic search. After reviewing published studies in which both GZMB and PRF were detected, data on the diagnostic accuracy of separate and combined evaluation of GZMB and PRF were pooled.
  
  
  RESULTS
  Across 16 studies (680 subjects), summary sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios with 95% confidence intervals were calculated. For overall GZMB analysis, the indices were 0.76 (0.71-0.81), 0.86 (0.82-0.89), 4.58 (3.36-6.25), and 0.32 (0.22-0.47), respectively. For overall PRF analysis, the indices were 0.83 (0.78-0.88), 0.86 (0.82-0.89), 4.82 (3.66-6.35), and 0.26 (0.18-0.37), respectively. Subgroup analyses showed similar results compared to overall study analyses. In analyses of combined evaluation of GZMB and PRF, the above indices were 0.65 (0.53-0.76), 0.96 (0.91-0.98), 12.66 (5.83-27.50), and 0.40 (0.23-0.69), respectively, when both markers were positive. The probability of developing AR in kidney transplant recipients increased from 15% to 73% when both GZMB and PRF tests were positive and was reduced to 2% if that were negative.
  
  
  CONCLUSIONS
  Currently, neither GZMB nor PRF, if evaluated alone, could be a convincing noninvasive diagnostic marker for AR in clinical practice. Combined use of PRF and GZMB post-kidney transplant may be a better choice in AR evaluation to direct allograft biopsy execution and earlier therapeutic intervention.
authors: Department of Urology, the First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People's Republic of China.
authors: Baoli
authors: B
authors: Heng
authors: Yunfei
authors: Y
authors: Li
authors: Liping
authors: L
authors: Shi
authors: Xinghua
authors: X
authors: Du
authors: Caiyong
authors: C
authors: Lai
authors: Long
authors: L
authors: Cheng
authors: Zexuan
authors: Z
authors: Su
mesh_terms: D000208:Acute Disease; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D006084:Graft Rejection / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D053804:Granzymes / Q000032:analysis* / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D016013:Likelihood Functions; D016017:Odds Ratio; D054353:Perforin / Q000032:analysis* / Q000235:genetics; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes