Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices

Author:

Ettenger Robert B.1ORCID,Seifert Michael E.2ORCID,Blydt‐Hansen Tom3ORCID,Briscoe David M.4ORCID,Holman John5ORCID,Weng Patricia L.1ORCID,Srivastava Rachana1ORCID,Fleming James5ORCID,Malekzadeh Mohammed1,Pearl Meghan1

Affiliation:

1. Division of Nephrology, Department of Pediatrics UCLA Mattel Children's Hospital, David Geffen School of Medicine at UCLA Los Angeles California USA

2. Division of Pediatric Nephrology, Department of Pediatrics University of Alabama at Birmingham Birmingham Alabama USA

3. Multi‐Organ Transplant Program, British Columbia Children's Hospital University of British Columbia Vancouver British Columbia Canada

4. Division of Nephrology, Department of Pediatrics Boston Children's Hospital Harvard Medical School Boston Massachusetts USA

5. Transplant Genomics Inc. Framingham Massachusetts USA

Abstract

ABSTRACTIntroductionThe successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short‐term graft survival. However, improvements in longer‐term outcomes have been much less apparent. One important contributor has been the phenomenon of low‐level rejection in the absence of clinical manifestations—so‐called subclinical rejection (SCR).MethodsTraditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.ResultsSerum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived‐cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.ConclusionSpecific emphasis is placed on studies carried out in pediatric kidney transplant recipients.Trial Registration: ClinicalTrials.gov: NCT03719339

Publisher

Wiley

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