Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Eikmans, Michael; Baelde, Hans J.; Hagen, E. C.; Paul, Leendert C.; Eilers, Paul H.C.; Heer, Emile de; Bruijn, Jan A.

doi:10.1097/01.asn.0000056611.92730.7b

Cited by 39 publications

(33 citation statements)

References 39 publications

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“…Despite the high number of published references on single gene analysis and chronic allograft injury (25)(26)(27)(28)(29)(30)(31), mechanisms and predictors of progressive alloimmune scarring remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Maluf

Mas

Archer

et al. 2008

Mol Med

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Loss of kidney graft function with tubular atrophy (TA) and interstitial fibrosis (IF) causes most kidney allograft losses. We aimed to identify the molecular pathways involved in IF/TA progression. Kidney biopsies from normal kidneys (n = 24), normal allografts (n = 6), and allografts with IF/TA (n = 17) were analyzed using high-density oligonucleotide microarray. Probe set level tests of hypotheses tests were conducted to identify genes with a significant trend in gene expression across the three groups using Jonckheere-Terpstra test for trend. Interaction networks and functional analysis were used. An unsupervised hierarchical clustering analysis showed that all the IF/TA samples were associated with high correlation. Gene ontology classified the differentially expressed genes as related to immune response, inflammation, and matrix deposition. Chemokines (CX), CX receptor (for example, CCL5 and CXCR4), interleukin, and interleukin receptor (for example, IL-8 and IL10RA) genes were overexpressed in IF/TA samples compared with normal allografts and normal kidneys. Genes involved in apoptosis (for example, CASP4 and CASP5) were importantly overexpressed in IF/TA. Genes related to angiogenesis (for example, ANGPTL3, ANGPT2, and VEGF) were downregulated in IF/TA. Genes related to matrix production-deposition were upregulated in IF/TA. A distinctive gene expression pattern was observed in IF/TA samples compared with normal allografts and normal kidneys. We were able to establish a trend in gene expression for genes involved in different pathways among the studied groups. The top-scored networks were related to immune response, inflammation, and cellto-cell interaction, showing the importance of chronic inflammation in progressive graft deterioration.

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Section: Discussionmentioning

confidence: 99%

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Maluf

Mas

Archer

et al. 2008

Mol Med

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“…The extent of interstitial fibrosis was assessed in Sirius red-stained paraffin sections, according to methods that have been described elsewhere (19). The percentage of the Sirius red-positive area of the total tubulointerstitial surface was quantified by digital image analysis (20). Histology of all biopsies was evaluated according to Banff 1997 criteria (21).…”

Section: Assessment Of Morphologic Alterationsmentioning

confidence: 99%

Expression of Surfactant Protein-C, S100A8, S100A9, and B Cell Markers in Renal Allografts

Eikmans¹,

Groningen²,

Sijpkens³

et al. 2005

Journal of the American Society of Nephrology

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The intent of this study was to identify genes of which expression during acute rejection is associated with progression to chronic allograft nephropathy using gene expression profiling. Ten patients who had graft loss through chronic allograft nephropathy (progression [PR] group) and 18 patients who had stable graft function over time (nonprogression [NP] group) were studied. Rejection severity and extent of infiltrating leukocytes in acute rejection biopsies were similar for both groups. Microarray analysis and real-time PCR validation showed that surfactant protein-C (SP-C), S100 calcium-binding protein A8 (S100A8), S100A9, and ␤-globin levels distinguished the two groups. Relationship between expression of B cell markers and prognosis was also examined. Location in the graft of the protein and mRNA expression of candidate genes was investigated. The prognostic value of mRNA transcripts was tested in an independent cohort of 43 rejection biopsies. mRNA and protein expression of S100A8 and S100A9 in infiltrating cells was significantly higher in the NP group compared with the PR group. Expression of SP-C was four-fold higher in the PR group and was detected in glomeruli. No association between B cell clusters and outcome was found. In the second group of acute rejection biopsies, SP-C mRNA levels predicted renal function course beyond 6 mo in multivariate analysis. Relatively high expression of S100A8 and S100A9 during acute rejection is associated with a favorable prognosis, and high SP-C expression is associated with an unfavorable prognosis. Messenger RNA transcripts complement the biopsy in the prediction of graft function deterioration.

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“…This method has been shown to be rapid and accurate in other clinical settings. 11,12 We therefore hypothesized that this technique may be an alternative way to diagnose preeclampsia.…”

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confidence: 99%

Quantitative Polymerase Chain Reaction–Based Analysis of Podocyturia Is a Feasible Diagnostic Tool in Preeclampsia

Kelder

Penning

et al. 2012

Hypertension

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Abstract-Preeclampsia is a significant cause of maternal and fetal morbidity and mortality worldwide. A clinically useful screening test that can predict development of preeclampsia at an early stage is urgently needed. The detection of podocyturia by immunohistochemistry after cell culture has been noted as a reliable marker for preeclampsia. However, this method is laborious and carries the risk of cell culture contamination. The aim of this study was to investigate the diagnostic value of quantitative polymerase chain reaction as a rapid method to detect preeclampsia. Clean-catch urine samples were collected from preeclamptic (n=35), healthy pregnant (n=34), and healthy nonpregnant (n=12) women. Furthermore, a control group of women with gestational hypertension (n=5) was included. Quantitative polymerase chain reaction analysis was performed for podocyte-specific markers. Receiver operating characteristic curve analyses were performed. Significantly elevated mRNA levels of nephrin, podocin, and vascular endothelial growth factor were detected in preeclamptic women compared with healthy pregnant and healthy nonpregnant controls. In addition, significantly elevated levels of nephrin mRNA were detected in urine of preeclamptic women compared with women with gestational hypertension. A positive correlation (ρ=0.82; P<0.0001) was observed between nephrin and vascular endothelial growth factor mRNA levels in preeclamptic women. Receiver operating characteristic curve analyses demonstrated a strong ability of this method to discriminate between the different study groups. Quantitative polymerase chain reaction analysis of podocyte-specific molecules in urine samples is a rapid and reliable method to quantify podocyturia. We demonstrate that this method distinguishes preeclamptic patients from healthy controls and women with gestational hypertension. This method may be a tool for the detection of preeclampsia at an earlier stage, thereby preventing maternal and fetal morbidity and mortality.

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Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Cited by 39 publications

References 39 publications

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Molecular Pathways Involved in Loss of Kidney Graft Function with Tubular Atrophy and Interstitial Fibrosis

Expression of Surfactant Protein-C, S100A8, S100A9, and B Cell Markers in Renal Allografts

Quantitative Polymerase Chain Reaction–Based Analysis of Podocyturia Is a Feasible Diagnostic Tool in Preeclampsia

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