Subthreshold rejection activity in many kidney transplants currently classified as having no rejection

. 2025 Jan ; 25 (1) : 72-87. [epub] 20240806

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid39117038
Odkazy

PubMed 39117038
DOI 10.1016/j.ajt.2024.07.034
PII: S1600-6135(24)00461-1
Knihovny.cz E-zdroje

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

1st Department of Nephrology and Transplantation With Dialysis Unit Medical University in Bialystok Poland

Albert Einstein College of Medicine Montefiore Medical Center USA

Alberta Transplant Applied Genomics Centre Canada

Cleveland Clinic Foundation USA

Department of Clinical Interventions Department of Nephrology and Kidney Transplantation SPWSZ Hospital Pomeranian Medical University Poland

Department of Immunology Transplantology and Internal Diseases Warsaw Medical University Poland

Department of Internal Medicine Division of Nephrology Virginia Commonwealth University USA

Department of Kidney Medicine Cleveland Clinic Foundation USA

Department of Kidney Medicine Glickman Urological and Kidney Institute Cleveland Clinic Foundation USA

Department of Laboratory Medicine University of Ulsan College of Medicine Assan Medical Center South Korea

Department of Medicine Division of Nephrology and Transplantation Immunology University of Alberta Canada

Department of Medicine Division of Nephrology University of Maryland USA

Department of Medicine Hennepin County Medical Centre USA

Department of Medicine Johns Hopkins University School of Medicine USA

Department of Medicine University of Wisconsin USA

Department of Nephrology and Kidney Transplantation Pomeranian Medical University Poland

Department of Nephrology and Transplant Center Institute for Experimental and Clinical Medicine Czech Republic

Department of Nephrology and Transplantation Medicine Medical University of Wrocław Poland

Department of Nephrology Charite Medical University of Berlin Germany

Department of Nephrology Institute for Experimental and Clinical Medicine Czech Republic

Department of Nephrology Kidney Transplantation and Hypertension The Children's Memorial Health Institute Poland

Department of Nephrology Medical University of Hannover Germany

Department of Nephrology The Royal Melbourne Hospital Australia

Department of Nephrology Transplant Center Institute for Experimental and Clinical Medicine Czech Republic

Department of Nephrology Transplantation and Internal Medicine Silesian Medical University Poland

Department of Nephrology Transplantology and Internal Diseases Medical University of Gdańsk Poland

Department of Nephrology Transplantology and Internal Medicine Medical University of Gdańsk Poland

Department of Nephrology Transplantology and Internal Medicine Pomeranian Medical University Poland

Department of Nephrology University Hospital Merkur Croatia

Department of Nephrology University of Ljubljana Slovenia

Department of Pathology University of Ljubljana Slovenia

Department of Renal Medicine Manchester Royal Infirmary United Kingdom

Department of Renal Research Manchester Royal Infirmary United Kingdom

Department of Surgery and Transplantation University Hospital Zurich Switzerland

Department of Surgery Division of Transplantation University on Minnesota USA

Department of Surgery Methodist Transplant and Specialty Hospital USA

Department of Surgery PinnacleHealth Transplant Associates USA

Department of Surgery University of Maryland USA

Department of Transplantation Medicine Warsaw Medical University Poland

Department of Transplantology Immunology Nephrology and Internal Diseases Warsaw Medical University Poland

Division of Nephrology and Comprehensive Transplant Center Department of Medicine Johns Hopkins University School of Medicine USA

Division of Nephrology and Dialysis Department of Medicine 3 Medical University of Vienna Austria

Division of Nephrology Department of Medicine University of Alabama at Birmingham USA

Division of Nephrology Department of Medicine University of Alberta USA

Division of Nephrology Department of Medicine Virginia Commonwealth University USA

Division of Nephrology University of Michigan USA

Division of Nephrology Washington University at St Louis USA

Henry Ford Transplant Institute USA

Intermountain Transplant Services USA

Johns Hopkins University School of Medicine USA

Kashi Clinical Laboratories USA

Nephrology and Kidney Transplantation Unit Nephrology Center Vilnius University Hospital Santaros Klinikos Lithuania

Nephrology Department University Hospital Zurich Switzerland

PinnacleHealth Transplant Associates USA

Pomeranian Medical University Poland

Renal Replacement Therapy Department of Nephrology University Hospital Merkur Croatia

St Paul's Hospital Canada

Tampa General Hospital USA

University Hospital Cleveland Medical Center USA

University Hospital no 1 Poland

University of Washington USA

Wojewodzki Hospital Poland

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