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Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy.

Nogare AL, Veronese FV, Carpio VN, Montenegro RM, Pedroso JA, Pegas KL, Gonçalves LF, Manfro RC - BMC Nephrol (2015)

Bottom Line: In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05).Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine.Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.

View Article: PubMed Central - PubMed

Affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. alnogare@gmail.com.

ABSTRACT

Background: Kidney injury molecule-1 (KIM-1) is expressed in tubular epithelial cells after injury and may have a role in the development of renal graft fibrosis. In this study we evaluated the molecular and protein expressions of KIM-1 in dysfunctional allografts and also mRNA KIM-1 expression in urine as potential biomarkers of graft fibrosis.

Methods: Protein and mRNA levels in renal tissue and urinary sediment cells of 69 kidney transplant recipients that undertook for-cause graft biopsies were evaluated by immunohistochemistry and real-time polymerase chain reaction. The histopathology was classified according to the 2007 Banff schema.

Results: KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubular atrophy (IF/TA) compared with biopsies showing acute calcineurin inhibitor nephrotoxicity (CIN) (P <0.05). Kidney tissue KIM-1 mRNA signaling (in) was increased in biopsies with IF/TA compared with all other groups (P <0.05). In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05). Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine.

Conclusions: KIM-1 seems to be a marker of kidney graft fibrosis. Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.

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The dot-plot representation graphics showing the medians and distribution of the quantification levels of normalized KIM-1 mRNA (2-ΔΔCT) according to the Banff diagnostic groups. Panel A: kidney tissue. Panel B: urinary sediment cells. ATN = acute tubular necrosis; AR = acute rejection; CIN = calcineurin inhibitor-induced nephrotoxicity; IFTA = interstitial fibrosis and tubular atrophy.
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Fig1: The dot-plot representation graphics showing the medians and distribution of the quantification levels of normalized KIM-1 mRNA (2-ΔΔCT) according to the Banff diagnostic groups. Panel A: kidney tissue. Panel B: urinary sediment cells. ATN = acute tubular necrosis; AR = acute rejection; CIN = calcineurin inhibitor-induced nephrotoxicity; IFTA = interstitial fibrosis and tubular atrophy.

Mentions: Tissue protein expression, measured semi-quantitatively, presented a higher value in the biopsies with a pathological diagnosis of IF/TA. The median KIM-1 protein expression in the IF/TA group [1.5 (1.0-2.0)] was significantly higher than the expression in the ATN [(1.0 (0.0-1.50)], AR [(1.0 (1.0-2.0)] or acute CIN group [0 (0.0 -0.0)] (P = 0.012). Biopsy staining scores of 2+ and 3+ were present in 50% of the grafts with IF/TA, compared to 11%, 22% and 25% of those with CIN, ATN and AR respectively. Tissue mRNA expression was also found to be significantly increased in the kidney biopsies classified in the IF/TA group as compared to all other groups (P <0.05), as shown in Figure 1A. Expression of the mRNA obtained from the cells of the urinary sediment provided a much less intense signal of expression. However, its expression was again significantly higher in the IF/TA group as compared with the acute CNI group (P <0.05) (Figure 1B). Importantly, it was found that a more intense protein expression is paralleled by a higher intensity of the mRNA signal, both in kidney tissue and USC (Table 2), and also that KIM-1 mRNA expression both in tissue and USC increased from IF/TA category I to III (Table 3).Figure 1


Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy.

Nogare AL, Veronese FV, Carpio VN, Montenegro RM, Pedroso JA, Pegas KL, Gonçalves LF, Manfro RC - BMC Nephrol (2015)

The dot-plot representation graphics showing the medians and distribution of the quantification levels of normalized KIM-1 mRNA (2-ΔΔCT) according to the Banff diagnostic groups. Panel A: kidney tissue. Panel B: urinary sediment cells. ATN = acute tubular necrosis; AR = acute rejection; CIN = calcineurin inhibitor-induced nephrotoxicity; IFTA = interstitial fibrosis and tubular atrophy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359521&req=5

Fig1: The dot-plot representation graphics showing the medians and distribution of the quantification levels of normalized KIM-1 mRNA (2-ΔΔCT) according to the Banff diagnostic groups. Panel A: kidney tissue. Panel B: urinary sediment cells. ATN = acute tubular necrosis; AR = acute rejection; CIN = calcineurin inhibitor-induced nephrotoxicity; IFTA = interstitial fibrosis and tubular atrophy.
Mentions: Tissue protein expression, measured semi-quantitatively, presented a higher value in the biopsies with a pathological diagnosis of IF/TA. The median KIM-1 protein expression in the IF/TA group [1.5 (1.0-2.0)] was significantly higher than the expression in the ATN [(1.0 (0.0-1.50)], AR [(1.0 (1.0-2.0)] or acute CIN group [0 (0.0 -0.0)] (P = 0.012). Biopsy staining scores of 2+ and 3+ were present in 50% of the grafts with IF/TA, compared to 11%, 22% and 25% of those with CIN, ATN and AR respectively. Tissue mRNA expression was also found to be significantly increased in the kidney biopsies classified in the IF/TA group as compared to all other groups (P <0.05), as shown in Figure 1A. Expression of the mRNA obtained from the cells of the urinary sediment provided a much less intense signal of expression. However, its expression was again significantly higher in the IF/TA group as compared with the acute CNI group (P <0.05) (Figure 1B). Importantly, it was found that a more intense protein expression is paralleled by a higher intensity of the mRNA signal, both in kidney tissue and USC (Table 2), and also that KIM-1 mRNA expression both in tissue and USC increased from IF/TA category I to III (Table 3).Figure 1

Bottom Line: In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05).Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine.Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.

View Article: PubMed Central - PubMed

Affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. alnogare@gmail.com.

ABSTRACT

Background: Kidney injury molecule-1 (KIM-1) is expressed in tubular epithelial cells after injury and may have a role in the development of renal graft fibrosis. In this study we evaluated the molecular and protein expressions of KIM-1 in dysfunctional allografts and also mRNA KIM-1 expression in urine as potential biomarkers of graft fibrosis.

Methods: Protein and mRNA levels in renal tissue and urinary sediment cells of 69 kidney transplant recipients that undertook for-cause graft biopsies were evaluated by immunohistochemistry and real-time polymerase chain reaction. The histopathology was classified according to the 2007 Banff schema.

Results: KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubular atrophy (IF/TA) compared with biopsies showing acute calcineurin inhibitor nephrotoxicity (CIN) (P <0.05). Kidney tissue KIM-1 mRNA signaling (in) was increased in biopsies with IF/TA compared with all other groups (P <0.05). In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05). Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine.

Conclusions: KIM-1 seems to be a marker of kidney graft fibrosis. Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.

Show MeSH
Related in: MedlinePlus