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Overexpression of BAX, NOL3, and XIAP Apoptotic Genes Participates in Calcineurin Inhibitors Nephrotoxicity: New Insights into Chronic Allograft Dysfunction

L. Garcia-Covarrubias,1 G. Queipo,2 M. Fonseca,2 D. Alcantara,1 P. Prieto,1 H. Diliz,1 A. Garcia,1 H. Hinojosa,1 A. Cicero,1 G. Melendez,3 M. Alamilla,3 R. Lascurain,4 V. Soto.5

1Transplantation, Hospital General de Mexico, Mexico City, Mexico
2Genetics, Hospital General de Mexico, Mexico City, Mexico
3Research, Hospital General de Mexico, Mexico City, Mexico
4Faculty of Medicine, UNAM, Mexico City, Mexico
5Pathology, Hospital General de Mexico, Mexico City, Mexico.

Meeting: 2018 American Transplant Congress

Abstract number: A84

Keywords: Apoptosis, Calcineurin, Gene expression, Nephrotoxicity

Session Information

Session Name: Poster Session A: Innate Immunity; Chemokines, Cytokines, Complement

Session Type: Poster Session

Date: Saturday, June 2, 2018

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

Introduction: Calcineurin inhibitors toxicity (CNIT) is a factor that limit the outcome of renal transplantation graft. The hypoxia causes histological data as nodular hyalinosis, hyalinosis, fibrosis, thrombotic microangiopathy, and isometric tubular vacuolization. The diagnosis requires an invasive procedure, an expert pathologist,and it is an exclusion diagnosis. Aim: Exploratory and descriptive study of the gene expression behavior of representative extrinsic and intrinsic apoptotic pathways in renal biopsies. Subjects and Methods: An Observational, descriptive cross sectional study was conducted. A convenience size of 7 renal biopsies samples was included from January to March 2017. The mRNA expression of renal tissue biopsies was analyzed using the RT2 Profiler PCR Array platform. Results: Two of five patients presented acute renal dysfunction with clinical and biochemical data with creatinine values of 2.5 mg/dl and CNIT values before the biopsy of 16ng/ml and 21 mg/ml respectively. The expression analyses of the genes associated directly with the inflammatory process (interleukins 2, 4, 6, 8, 10, TNF alpha, and TNF beta) showed in all the cases and also in the controls the absence of any detectable transcript in all the cytokines studied. The QPCR arrays showed that Bcl-2-associated X protein (BAX), Nucleolar Protein 3 (NOL3) and X-Linked Inhibitor of Apoptosis (XIAP) were consistent only in the CNIT patients. This result suggests that in the group of patients with CNIT BAX is activated, this gene is a key player in the intrinsic apoptosis pathway, suggesting that apoptosis via mitochondria is turn on probably due to the arteriolar vasoconstriction and the hypoxic state. Conclusions: We proposed that intrinsic apoptotic pathway plays a relevant role in the physiopathology of the CNIT.

CITATION INFORMATION: Garcia-Covarrubias L., Queipo G., Fonseca M., Alcantara D., Prieto P., Diliz H., Garcia A., Hinojosa H., Cicero A., Melendez G., Alamilla M., Lascurain R., Soto V. Overexpression of BAX, NOL3, and XIAP Apoptotic Genes Participates in Calcineurin Inhibitors Nephrotoxicity: New Insights into Chronic Allograft Dysfunction Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Garcia-Covarrubias L, Queipo G, Fonseca M, Alcantara D, Prieto P, Diliz H, Garcia A, Hinojosa H, Cicero A, Melendez G, Alamilla M, Lascurain R, Soto V. Overexpression of BAX, NOL3, and XIAP Apoptotic Genes Participates in Calcineurin Inhibitors Nephrotoxicity: New Insights into Chronic Allograft Dysfunction [abstract]. https://atcmeetingabstracts.com/abstract/overexpression-of-bax-nol3-and-xiap-apoptotic-genes-participates-in-calcineurin-inhibitors-nephrotoxicity-new-insights-into-chronic-allograft-dysfunction/. Accessed May 12, 2025.

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