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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 ABMR, TCMR, 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95611 | GEO | 2017/04/27

SECONDARY ACCESSION(S): PRJNA377667

REPOSITORIES: GEO

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The effect of cortex/medulla proportions on molecular diagnoses in kidney transplant biopsies: rejection and injury can be assessed in medulla

Project description: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 ABMR, TCMR, 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. We studied 26 pairs of cortex/medulla biopsies from 26 patients (4 unpaired), characterizing the clinical and histological features, and defined the mRNA phenotype with Affymetrix expression microarrays. We also studied 37 pairs of biopsies from biological replicates and 12 pairs from technical replicates. This dataset is part of the TransQST collection.

2017-04-27 | E-GEOD-95611 | biostudies-arrayexpress

Homo sapiens

Project description:The effect of cortex/medulla proportions on molecular diagnoses in kidney transplant biopsies: rejection and injury can be assessed in medulla

| PRJNA377667 | ENA

Microarray profiling of renal medulla / papilla and cortex during postnatal development

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The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study

Project description:Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. Groups differed in median time post-transplant e.g. R3injury 99 days vs. R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts e.g. intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (e.g. hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR, R3injury, and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical ABMR were present in the population, and strategies that previously revealed antibody-mediated rejection (ABMR) in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.

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2016-01-12 | E-GEOD-72128 | biostudies-arrayexpress

Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes

Project description:Previous studies of rejection-associated transcript expression in heart transplant biopsies identified not only rejection but a group of early biopsies with injury but no rejection. The present analysis used an expanded population of biopsies to explore parenchymal injury in all biopsies, with or without rejection, and its relationship to function, and outcome. Archetypal analysis defined five injury clusters: no-injury (N=376); mild (N=526); moderate (N=110); severe (N=87); and late (N=221). The late group, 62% of which had no rejection, had molecular characteristics associated with atrophy-fibrosis, depressed LVEF, and increased graft loss independent of rejection status. In random forest analysis, low LVEF was more strongly associated with injury scores than with rejection scores. Three-year graft failure was best predicted using a combination of injury and rejection scores. In heart transplant biopsies, injury-related molecular scores correlate with dysfunction and risk of failure and identify an important new group of late heart transplants, many with no rejection, that have impaired function and a high risk of graft loss. (ClinicalTrials.gov #NCT02670408).

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