Efeito da isquemia renal unilateral no rim contralateral avaliada pela expressão de Caspase 3
Effect of unilateral renal ischemia on the contralateral kidney assessed by Caspase 3 expression
Carolina Rodrigues Dal Bo; Vitória Penido de Paula; Anna Paula Weinhardt Baptista Strazzi; Nelson Wolosker; Thiago Pinheiro Arrais Aloia; Angela Mazzeo; Oskar Grau Kaufmann
Background: Studies have demonstrated with histological analysis and Doppler flow measurement analysis that unilateral renal ischemia, which is performed in some surgeries, interfered with the contralateral kidney, identifying the phenomenon of kidney-kidney crosstalk. Objectives: To identify the effects on the ischemic and contralateral kidney of renal ischemia induced by two types of clamping technique by analyzing the volume of kidney cells positive for Caspase 3. Methods: Sixteen pigs were divided into 2 groups, as follows: A (n = 8) – clamping of left renal artery only and AV (n = 8) – clamping of left renal artery and vein. Immunohistochemical analyses (anti Caspase 3) were conducted with biopsy specimens collected from the ischemic and contralateral kidney at 0, 30, 60, and 90 minutes of ischemia and morphometric analysis was performed, taking the mean to represent the volume of the Caspase 3 positive area (%). Results: Morphometric analysis of specimens collected at 30, 60, and 90 minutes of ischemia showed that the mean area marked for Caspase 3 was statistically larger in the contralateral kidney than the ischemic kidney in both groups: clamped renal artery (A) and clamped renal artery and vein (AV). Comparing the ischemic and contralateral kidney, there was no statistically significant difference in the area marked for Caspase 3 between the two types of clamping. Conclusions: In the experimental model of unilateral renal ischemia, the non-ischemic kidney exhibited cell damage, demonstrated by Caspase 3 expression. The type of hilum clamping does not appear to influence the area marked for Caspase 3
1 Abuelo JG. Normotensive ischemic acute renal failure. N Engl J Med. 2007;357(8):797-805.
2 Badr KF, Ichikawa I. Prerenal failure: a deleterious shift from renal compensation to decompensation. N Engl J Med. 1988;319(10):623-9.
3 Simmons MN, Schreiber MJ, Gill IS. Surgical renal ischemia: a contemporary overview. J Urol. 2008;180(1):19-30.
4 Himmelfarb J, Joannidis M, Molitoris B, et al. Evaluation and initial management of acute kidney injury. Clin J Am Soc Nephrol. 2008;3(4):962-7.
5 Orvieto MA, Zorn KC, Mendiola F, et al. Recovery of renal function after complete renal hilar versus artery alone clamping during open and laparoscopic surgery. J Urol. 2007;177(6):2371-4.
6 Kerbl K, Chandhoke PS, Clayman RV, McDougall E, Stone AM, Figenshau RS. Ligation of the renal pedicle during laparoscopic nephrectomy: a comparison of staples, clips, and sutures. J Laparoendosc Surg. 1993;3(1):9-12.
7 Gardner DS, De Brot S, Dunford LJ, et al. Remote effects of acute kidney injury in a porcine model. Am J Physiol Renal Physiol. 2016;310(4):F259-71.
8 Crane NJ, Huffman SW, Alemozaffar M, Gage FA, Levin IW, Elster EA. Evidence of a heterogeneous tissue oxygenation: renal ischemia/reperfusion injury in a large animal model. J Biomed Opt. 2013;18(3):035001.
9 Oishi Y, Manabe I. Organ system crosstalk in cardiometabolic disease in the age of multimorbidity. Front Cardiovasc Med. 2020;7:64.
10 Baptista Sincos AP, Mazzeo A, Sincos IR, et al. Duplex scan and histologic assessment of acute renal injury in a kidney-kidney crosstalk swine experimental model. J Vasc Surg. 2018;68(2):588-95.
11 Mazzeo A, Sincos APB, Leite KRM, Goes MA Jr, Pavão OFS, Kaufmann OG. Study of kidney morphologic and structural changes related to different ischemia times and types of clamping of the renal vascular pedicle. Int Braz J Urol. 2019;45(4):754-62.
12 Yanagihara T, Yoshimine T, Morimoto K, Yamamoto K, Homburger HA. Immunohistochemical Investigation of Cerebral Ischemia in Gerbils. J Neuropathol Exp Neurol. 1985;44(2):204-15.
13 Mondello C, Cardia L, Ventura-Spagnolo E. Immunohistochemical detection of early myocardial infarction: a systematic review. Int J Legal Med. 2017;131(2):411-21.
14 Aljakna A, Fracasso T, Sabatasso S. Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers. Int J Legal Med. 2018;132(2):425-38.
15 Mondello C, Cardia L, Bartoloni G, Asmundo A, Ventura Spagnolo E. Immunohistochemical study on dystrophin expression in CAD-related sudden cardiac death: a marker of early myocardial ischaemia. Int J Legal Med. 2018;132(5):1333-9.
16 Faubel S, Edelstein CL. Caspases as drug targets in ischemic organ injury. Curr Drug Target Immune Endocr Metabol Disord. 2005;5(3):269-87.
17 Belczak SQ. Tratamento endovascular de trauma arterial periférico com o uso de stents revestidos: estudo experimental em porcos [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2011.
18 Lederman A. Indução de aneurisma em aorta abdominal de porcos: um modelo endovascular [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2015.
19 R Core Team. R: A language and environment for statistical computing [software]. New Zeland: R Foundation for Statistical Computing; 2017. [cited 2021 jan 18]. https://www.R-project.org/.
20 Morettin PA, Bussab WO. Medidas-Resumo. In: Morettin PA, Bussab WO, editors. Estatística básica. São Paulo: Saraiva; 2010. p. 35-56.
21 Faraway JJ. Multinomial Data. In: Faraway JJ, editor. Extending the linear model with R: generalized linear, mixed effects and nonparametric regression models. Boca Raton: Chapman & Hall/CRC; 2016. p. 129-50.
22 Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol. 2003;14(8):2199-210.
23 Secin FP. Importance and limits of ischemia in renal partial surgery: experimental and clinical research. Adv Urol. 2008;2008:102461.
24 Goes N, Urmson J, Ramassar V, Halloran PF. Ischemic acute tubular necrosis induces an extensive local cytokine response. Evidence for induction of interferon-gamma, transforming growth factor-beta 1, granulocyte-macrophage colony-stimulating factor, interleukin-2, and interleukin-10. Transplantation. 1995;59(4):565-72.
25 Jablonski P, Howden B, Rae D, et al. The influence of the contralateral kidney upon recovery from unilateral warm renal ischemia. Pathology. 1985;17(4):623-7.
26 Armutcu F. Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions. Inflamm Res. 2019;68(10):825-39.
27 Giraud S, Favreau F, Chatauret N, Thuillier R, Maiga S, Hauet T. Contribution of large pig for renal ischemia-reperfusion and transplantation studies: the preclinical model. J Biomed Biotechnol. 2011;532127.