title: The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla.
abstract: Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL, and REN). Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the molecular microscope diagnostic system. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had <50% cortex. Molecular scores for antibody-mediated rejection, T cell-mediated rejection, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection; and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex.
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada.
authors.forename: K S
authors.initials: KS
authors.lastname: Madill-Thomsen
authors.affiliation: Nephrology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
authors.forename: R C
authors.initials: RC
authors.lastname: Wiggins
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Eskandary
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: G A
authors.initials: GA
authors.lastname: Böhmig
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada.|Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: P F
authors.identifier: http://orcid.org/0000-0003-1371-1947
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival; D006801:Humans; D007672:Kidney Cortex / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000601:surgery; D007679:Kidney Medulla / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: biopsy; clinical research/practice; kidney biology; kidney transplantation/nephrology; microarray/gene array; molecular biology; molecular biology: mRNA/mRNA expression; rejection