Post-mortem assessment of vimentin expression as a biomarker for renal tubular regeneration following acute kidney injury
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E.Methods: We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression.Results: Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression.Conclusions: In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.
Abstract
Background: Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E.Methods: We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression.Results: Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression.Conclusions: In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.
참고문헌 (47)
- Eknoyan G, "On improving outcomes and quality of dialysis care, and more", Am J Kidney Dis, 39, pp.889~891 (2002)
- Makris K, "Acute kidney injury : definition, pathophysiology and clinical phenotypes", Clin Biochem Rev, 37, pp.85~98 (2016)
- Akcay A, "Update on the diagnosis and management of acute kidney injury", Int J Nephrol Renovasc Dis, 3, pp.129~140 (2010)
- Basile DP, "Pathophysiology of acute kidney injury", Compr Physiol, 2, pp.1303~1353 (2012)
- Sawhney S, "Epidemiology of AKI : utilizing large databases to determine the burden of AKI", Adv Chronic Kidney Dis, 24, pp.194~204 (2017)
- Siew ED, "The growth of acute kidney injury : a rising tide or just closer attention to detail?", Kidney Int, 87, pp.46~61 (2015)
- Hoste EA, "Global epidemiology and outcomes of acute kidney injury", Nat Rev Nephrol, 14, pp.607~625 (2018)
- Pugh D, "Management of hypertension in chronic kidney disease", Drugs, 79, pp.365~379 (2019)
- Schoolwerth AC, "Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Renal considerations in angiotensin converting enzyme inhibitor therapy:a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association", Circulation, 104, pp.1985~1991 (2001)
- Rosen S, "Acute tubular necrosis is a syndrome of physiologic and pathologic dissociation", J Am Soc Nephrol, 19, pp.871~875 (2008)
- Berger K, "Mechanisms of epithelial repair and regeneration after acute kidney injury", Semin Nephrol, 34, pp.394~403 (2014)
- Wen Y, "A systematic review of clinical characteristics and histologic descriptions of acute tubular injury", Kidney Int Rep, 5, pp.1993~2001 (2020)
- Toback FG, "Regeneration after acute tubular necrosis", Kidney Int, 41, pp.226~246 (1992)
- Bonventre JV., "Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure", J Am Soc Nephrol, 14(Suppl 1), pp.S55~S61 (2003)
- Andrianova NV, "Kidney cells regeneration : dedifferentiation of tubular epithelium, resident stem cells and possible niches for renal progenitors", Int J Mol Sci, 20, pp.6326~ (2019)
- Solez K, "The morphology of"acute tubular necrosis"in man : analysis of 57 renal biopsies and a comparison with the glycerol model", Medicine(Baltimore), 58, pp.362~376 (1979)
- Molitoris BA, "Characterization of ischemia-induced loss of epithelial polarity", J Membr Biol, 106, pp.233~242 (1988)
- Witzgall R, "Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells", J Clin Invest, 93, pp.2175~2188 (1994)
- Fujigaki Y, "Kinetics and characterization of initially regenerating proximal tubules in S3 segment in response to various degrees of acute tubular injury", Nephrol Dial Transplant, 21, pp.41~50 (2006)
- Frazier KS, "Proliferative and nonproliferative lesions of the rat and mouse urinary system", Toxicol Pathol., 40(4 Suppl), pp.14S~86S (2012)
- Schena FP, "Role of growth factors in acute renal failure", Kidney Int Suppl, 66, pp.S11~S15 (1998)
- Devarajan P, "Gene expression in early ischemic renal injury : clues towards pathogenesis, biomarker discovery, and novel therapeutics", Mol Genet Metab, 80, pp.365~376 (2003)
- Joh K, "Renal pathology of ANCA-related vasculitis : proposal for standardization of pathological diagnosis in Japan", Clin Exp Nephrol, 12, pp.277~291 (2008)
- Textor SC, "Vascular medicine: a companion to Braunwald's heart disease", pp.285~295 (2013), W.B. Saunders
- Breshears MA, "Pathologic basis of veterinary disease", pp.617~681 (2017), Elsevier
- Mehendiratta M, "Ghost cells: a journey in the dark", Dent Res J (Isfahan), 9(Suppl 1), pp.S1~S8 (2012)
- Gonlusen G, "The expression of cytoskeletal proteins(alpha-SMA, vimentin, desmin)in kidney tissue : a comparison of fetal, normal kidneys, and glomerulonephritis", Int Urol Nephrol, 33, pp.299~305 (2001)
- Inker LA, "Estimating glomerular filtration rate using the chronic kidney disease-epidemiology collaboration creatinine equation : better risk predictions", Circ Heart Fail, 5, pp.303~306 (2012)
- Smeets B, "Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration", J Pathol, 229, pp.645~659 (2013)
- Robinson-Bennett B, "Handbook of immunohistochemistry and in situ hybridization of human carcinomas", pp.537~545 (2006), Elsevier Academic Press
- Kokkinos MI, "Vimentin and epithelial-mesenchymal transition in human breast cancer : observations in vitro and in vivo", Cells Tissues Organs, 185, pp.191~203 (2007)
- Holthofer H, "Expression of vimentin and cytokeratin types of intermediate filament proteins in developing and adult human kidneys", Lab Invest, 50, pp.552~559 (1984)
- Mezni I, "Tubular expression of vimentin as a biomarker of kidney graft fibrogenesis : invasive and noninvasive measurements : abstract# A22", Transplantation, 98, pp.877~ (2014)
- Vogetseder A, "Tubular cell proliferation in the healthy rat kidney", Histochem Cell Biol, 124, pp.97~104 (2005)
- Chambers BE, "Renal progenitors : roles in kidney disease and regeneration", World J Stem Cells, 8, pp.367~375 (2016)
- Maeshima A, "Identification of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney", J Am Soc Nephrol, 14, pp.3138~3146 (2003)
- Kitamura S, "Establishment and characterization of renal progenitor like cells from S3 segment of nephron in rat adult kidney", FASEB J, 19, pp.1789~1797 (2005)
- Bussolati B, "Isolation of renal progenitor cells from adult human kidney", Am J Pathol, 166, pp.545~555 (2005)
- Kim K, "Adult stem cell-like tubular cells reside in the corticomedullary junction of the kidney", Int J Clin Exp Pathol, 1, pp.232~241 (2008)
- Cheaito KA, "EMT markers in locally-advanced prostate cancer : predicting recurrence?", Front Oncol, 9, pp.131~ (2019)
- Hansson J, "Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney", Hum Pathol, 45, pp.382~393 (2014)
- Vansthertem D, "Label-retaining cells and tubular regeneration in postischaemic kidney", Nephrol Dial Transplant, 23, pp.3786~3797 (2008)
- Wolters PJ, "Pathogenesis of idiopathic pulmonary fibrosis", Annu Rev Pathol, 9, pp.157~179 (2014)
- 이수진, "The expression and secretion of vimentin in the progression of non-alcoholic steatohepatitis", BMB Reports, 47(8), pp.457~462 (2014), 생화학분자생물학회
- Li FJ, "Autoimmunity to vimentin is associated with outcomes of patients with idiopathic pulmonary fibrosis", J Immunol, 199, pp.1596~1605 (2017)
- Danielsson F, "Vimentin diversity in health and disease", Cells, 7, pp.147~ (2018)
- Policy PP., "Minimum period of retention of laboratory records and materials" (2020), College of American Pathologists