Novel non-invasive biomarkers diagnostic of acute rejection in renal transplant recipients: A systematic review.

Abstract

Acute rejection is a significant complication detrimental to kidney transplant function. Current accepted means of diagnosis is percutaneous renal biopsy, a costly and invasive procedure. There is an urgent need to detect and validate non-invasive biomarkers capable of replacing the biopsy. Comprehensive literature searches of Medline, EMBASE and Cochrane Central Register of Controlled Trials databases were performed. Eligible studies were included as per inclusion criteria and assessed for quality using the GRADE quality of evidence tool. Outcomes evaluated included biomarker diagnostic performance, number of patients/samples, mean age and gender ratio, immunosuppression regime, in addition to clinical applications of the biomarker(s) tested. PRISMA guidelines were followed. Where possible, statistical analysis of comparative performance data was performed. 23 studies were included in this review, including 19 adult, 3 paediatric and 1 mixed studies. A total of 2858 participants and 50 candidate non-invasive tests were identified. Sensitivity, specificity and area under the curve performance values ranged 36%-100%, 30%-100% and 0.55-0.98, respectively. Although larger, more robust multi-centre validation studies are needed before non-invasive biomarkers can replace the biopsy, numerous candidate tests have demonstrated significant promise for various facets of postoperative management. Suggested uses include: ruling out patients with a low risk of acute rejection to avoid the need for biopsy, non-invasive testing where the biopsy is contraindicated and a prompt diagnosis is needed, and integration into a serial blood monitoring protocol in conjunction with serum creatinine.