Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers

Valeria Mas, Daniel Maluf, Kellie Archer, Kenneth Yanek, Luciana Mas, Anne King, Eric Gibney, Davis Massey, Adrian Cotterell, Robert Fisher, Marc Posner

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Chronic allograft nephropathy (CAN) is a cause of graft loss. The multistage processes that result in CAN are poorly understood. Noninvasive assays for detecting allograft dysfunction and predicting long-term outcomes are a priority in transplantation (Tx). METHODS. Renal tissue from kidney transplant patients (KTP) with CAN (n=11) and normal kidneys (NK; n=7) were studied using microarrays. Markers resulting from the microarray analysis (transforming growth factor [TGF]-β, epidermal growth factor receptor [EGFR], angiotensinogen [AGT]) were tested in urine (Ur) and peripheral blood (PB) samples from the CAN patients (collected at the biopsy time) using reverse-transcriptase real-time polymerase chain reaction. Ur and PB samples from long-term KTP with stable renal function (SRF; n=20) were used as control. RESULTS. Assuming unequal variances between CAN and NK, using a false discovery rate of 0.005, and running 1,000 of all possible permutations, 728 probe sets were differentially expressed. Genes related to fibrosis and extracellular matrix deposition (i.e., TGF-β, laminin, gamma 2, metalloproteinases-9, and collagen type IX alpha 3) were up-regulated. Genes related to immunoglobulins, B cells, T-cell receptor, nuclear factor of activated T cells, and cytokine and chemokines receptors were also upregulated. EGFR and growth factor receptor activity (FGFR)2 were downregulated in CAN samples. AGT, EGFR, and TGF-β levels were statistical different in urine but not in blood samples of CAN patients when compared to KTP with SRF (P<0.001, P=0.04, and P<0.001, respectively). CONCLUSIONS. Genes related to fibrosis, extracellular matrix deposition, and immune response were found up-regulated in CAN. Markers resulting from the microarray analysis were differentially expressed in Ur samples of the CAN patients and in concordance with the microarray profiles.

Original languageEnglish (US)
Pages (from-to)448-457
Number of pages10
JournalTransplantation
Volume83
Issue number4
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

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Allografts
Kidney
Transforming Growth Factors
Epidermal Growth Factor Receptor
Urine
Transplants
Angiotensinogen
Microarray Analysis
Extracellular Matrix
Fibrosis
Collagen Type IX
Genes
NFATC Transcription Factors
Growth Factor Receptors
Chemokine Receptors
Metalloproteases
Laminin
T-Cell Antigen Receptor
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers. / Mas, Valeria; Maluf, Daniel; Archer, Kellie; Yanek, Kenneth; Mas, Luciana; King, Anne; Gibney, Eric; Massey, Davis; Cotterell, Adrian; Fisher, Robert; Posner, Marc.

In: Transplantation, Vol. 83, No. 4, 01.02.2007, p. 448-457.

Research output: Contribution to journalArticle

Mas, V, Maluf, D, Archer, K, Yanek, K, Mas, L, King, A, Gibney, E, Massey, D, Cotterell, A, Fisher, R & Posner, M 2007, 'Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers', Transplantation, vol. 83, no. 4, pp. 448-457. https://doi.org/10.1097/01.tp.0000251373.17997.9a
Mas, Valeria ; Maluf, Daniel ; Archer, Kellie ; Yanek, Kenneth ; Mas, Luciana ; King, Anne ; Gibney, Eric ; Massey, Davis ; Cotterell, Adrian ; Fisher, Robert ; Posner, Marc. / Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers. In: Transplantation. 2007 ; Vol. 83, No. 4. pp. 448-457.
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abstract = "BACKGROUND. Chronic allograft nephropathy (CAN) is a cause of graft loss. The multistage processes that result in CAN are poorly understood. Noninvasive assays for detecting allograft dysfunction and predicting long-term outcomes are a priority in transplantation (Tx). METHODS. Renal tissue from kidney transplant patients (KTP) with CAN (n=11) and normal kidneys (NK; n=7) were studied using microarrays. Markers resulting from the microarray analysis (transforming growth factor [TGF]-β, epidermal growth factor receptor [EGFR], angiotensinogen [AGT]) were tested in urine (Ur) and peripheral blood (PB) samples from the CAN patients (collected at the biopsy time) using reverse-transcriptase real-time polymerase chain reaction. Ur and PB samples from long-term KTP with stable renal function (SRF; n=20) were used as control. RESULTS. Assuming unequal variances between CAN and NK, using a false discovery rate of 0.005, and running 1,000 of all possible permutations, 728 probe sets were differentially expressed. Genes related to fibrosis and extracellular matrix deposition (i.e., TGF-β, laminin, gamma 2, metalloproteinases-9, and collagen type IX alpha 3) were up-regulated. Genes related to immunoglobulins, B cells, T-cell receptor, nuclear factor of activated T cells, and cytokine and chemokines receptors were also upregulated. EGFR and growth factor receptor activity (FGFR)2 were downregulated in CAN samples. AGT, EGFR, and TGF-β levels were statistical different in urine but not in blood samples of CAN patients when compared to KTP with SRF (P<0.001, P=0.04, and P<0.001, respectively). CONCLUSIONS. Genes related to fibrosis, extracellular matrix deposition, and immune response were found up-regulated in CAN. Markers resulting from the microarray analysis were differentially expressed in Ur samples of the CAN patients and in concordance with the microarray profiles.",
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T1 - Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers

AU - Mas, Valeria

AU - Maluf, Daniel

AU - Archer, Kellie

AU - Yanek, Kenneth

AU - Mas, Luciana

AU - King, Anne

AU - Gibney, Eric

AU - Massey, Davis

AU - Cotterell, Adrian

AU - Fisher, Robert

AU - Posner, Marc

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N2 - BACKGROUND. Chronic allograft nephropathy (CAN) is a cause of graft loss. The multistage processes that result in CAN are poorly understood. Noninvasive assays for detecting allograft dysfunction and predicting long-term outcomes are a priority in transplantation (Tx). METHODS. Renal tissue from kidney transplant patients (KTP) with CAN (n=11) and normal kidneys (NK; n=7) were studied using microarrays. Markers resulting from the microarray analysis (transforming growth factor [TGF]-β, epidermal growth factor receptor [EGFR], angiotensinogen [AGT]) were tested in urine (Ur) and peripheral blood (PB) samples from the CAN patients (collected at the biopsy time) using reverse-transcriptase real-time polymerase chain reaction. Ur and PB samples from long-term KTP with stable renal function (SRF; n=20) were used as control. RESULTS. Assuming unequal variances between CAN and NK, using a false discovery rate of 0.005, and running 1,000 of all possible permutations, 728 probe sets were differentially expressed. Genes related to fibrosis and extracellular matrix deposition (i.e., TGF-β, laminin, gamma 2, metalloproteinases-9, and collagen type IX alpha 3) were up-regulated. Genes related to immunoglobulins, B cells, T-cell receptor, nuclear factor of activated T cells, and cytokine and chemokines receptors were also upregulated. EGFR and growth factor receptor activity (FGFR)2 were downregulated in CAN samples. AGT, EGFR, and TGF-β levels were statistical different in urine but not in blood samples of CAN patients when compared to KTP with SRF (P<0.001, P=0.04, and P<0.001, respectively). CONCLUSIONS. Genes related to fibrosis, extracellular matrix deposition, and immune response were found up-regulated in CAN. Markers resulting from the microarray analysis were differentially expressed in Ur samples of the CAN patients and in concordance with the microarray profiles.

AB - BACKGROUND. Chronic allograft nephropathy (CAN) is a cause of graft loss. The multistage processes that result in CAN are poorly understood. Noninvasive assays for detecting allograft dysfunction and predicting long-term outcomes are a priority in transplantation (Tx). METHODS. Renal tissue from kidney transplant patients (KTP) with CAN (n=11) and normal kidneys (NK; n=7) were studied using microarrays. Markers resulting from the microarray analysis (transforming growth factor [TGF]-β, epidermal growth factor receptor [EGFR], angiotensinogen [AGT]) were tested in urine (Ur) and peripheral blood (PB) samples from the CAN patients (collected at the biopsy time) using reverse-transcriptase real-time polymerase chain reaction. Ur and PB samples from long-term KTP with stable renal function (SRF; n=20) were used as control. RESULTS. Assuming unequal variances between CAN and NK, using a false discovery rate of 0.005, and running 1,000 of all possible permutations, 728 probe sets were differentially expressed. Genes related to fibrosis and extracellular matrix deposition (i.e., TGF-β, laminin, gamma 2, metalloproteinases-9, and collagen type IX alpha 3) were up-regulated. Genes related to immunoglobulins, B cells, T-cell receptor, nuclear factor of activated T cells, and cytokine and chemokines receptors were also upregulated. EGFR and growth factor receptor activity (FGFR)2 were downregulated in CAN samples. AGT, EGFR, and TGF-β levels were statistical different in urine but not in blood samples of CAN patients when compared to KTP with SRF (P<0.001, P=0.04, and P<0.001, respectively). CONCLUSIONS. Genes related to fibrosis, extracellular matrix deposition, and immune response were found up-regulated in CAN. Markers resulting from the microarray analysis were differentially expressed in Ur samples of the CAN patients and in concordance with the microarray profiles.

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