Your browser doesn't support javascript.
loading
Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.
Gupta, Gaurav; Moinuddin, Irfan; Kamal, Layla; King, Anne L; Winstead, Ryan; Demehin, Moses; Kang, Le; Kimball, Pamela; Levy, Marlon; Bhati, Chandra; Massey, H Davis; Kumar, Dhiren; Halloran, Philip F.
Afiliação
  • Gupta G; Division of Nephrology, Virginia Commonwealth University, Richmond, VA.
  • Moinuddin I; Division of Nephrology, Virginia Commonwealth University, Richmond, VA.
  • Kamal L; Division of Nephrology, Virginia Commonwealth University, Richmond, VA.
  • King AL; Division of Nephrology, Virginia Commonwealth University, Richmond, VA.
  • Winstead R; Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA.
  • Demehin M; Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA.
  • Kang L; Department of Biostatistics, Virginia Commonwealth University, Richmond, VA.
  • Kimball P; Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA.
  • Levy M; Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA.
  • Bhati C; Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA.
  • Massey HD; Department of Pathology, Virginia Commonwealth University, Richmond, VA.
  • Kumar D; Division of Nephrology, Virginia Commonwealth University, Richmond, VA.
  • Halloran PF; Alberta Transplant Applied Genomics Center, Edmonton, AB, Canada.
Transplantation ; 106(5): 1061-1070, 2022 05 01.
Article em En | MEDLINE | ID: mdl-34075006
ABSTRACT

BACKGROUND:

Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology.

METHODS:

In this single-center prospective study of 208 biopsies (median = 5.8 mo) posttransplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cutoffs ≤ 0.21% to "rule-out" rejection and ≥1% to "rule-in" rejection.

RESULTS:

There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T cell-mediated rejection [TCMR; histology 27 (13%) versus MMDx 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC for cfDNA and prediction of rejection were slightly better with MMDx (AUC = 0.80; 95% CI 0.74-0.86) versus histology (AUC = 0.75; 95% CI 0.69-0.81). A cfDNA ≤ 0.21% had similar sensitivity (~91%) to "rule-out" rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to "rule-in" rejection using cfDNA criterion ≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury for both "rejection" and "nonrejection" biopsies.

CONCLUSIONS:

Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular acute kidney injury suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Injúria Renal Aguda / Ácidos Nucleicos Livres Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Injúria Renal Aguda / Ácidos Nucleicos Livres Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article