Introdução: O transplante renal é amplamente reconhecido como a melhor forma de tratamento para os pacientes que necessitam de terapia de substituição renal. Frequentemente a equipe transplantadora se depara com a difícil questão de determinar se órgãos, provenientes de doadores falecidos e limítrofes ou em parada cardíaca, estão aptos para serem transplantados. É difícil quantificar a intensidade do dano provocado pela isquemia no enxerto a ser utilizado, especialmente se o doador apresentou quadro de instabilidade hemodinâmica com queda significativa da perfusão tecidual e aumento do risco de diminuir a função do enxerto e afetar adversamente sua sobrevida. Desta forma torna-se justificável a utilização da técnica de espectroscopia de fluorescência induzida pelo laser, na tentativa de se avaliar a correlação entre os seus achados e o grau de lesão histológica renal experimental, uma vez que se trata de um método objetivo, não invasivo, rápido e em tempo real que, futuramente, pode ser aplicada nos transplantes renais em humanos. Objetivos: Avaliar a correlação entre os dados da espectroscopia de fluorescência induzida pelo laser e alterações histológicas na isquemia e reperfusão renal em ratos, e se existe diferença significativa na leitura da espectroscopia entre os polos superior, inferior e o terço médio. Materiais e Métodos: Foram utilizados 33 ratos (Rattus norvegicus) machos adultos da linhagem Wistar que, depois de anestesiados, tiveram seus rins esquerdos abordados. Inicialmente os rins foram submetidos à detecção da espectroscopia de fluorescência dos pólos superiores, inferiores e terços médios. As excitações foram geradas por lasers com comprimentos de onda de 408, 442 e 532 nm. Em seguida os pedículos renais esquerdos foram dissecados, isolados e clampeados com auxílio de mini-pinça vascular. Então, os animais foram divididos aleatoriamente em três grupos isquêmicos de 30, 60 e 120 minutos de isquemia quente. Em cada um dos grupos, os rins foram novamente analisados pela espectroscopia de fluorescência, bem como após 5 minutos de reperfusão, utilizando novamente feixes excitatórios com os mesmos comprimentos de onda, nas mesmas regiões renais. Posteriormente os rins esquerdos foram coletados e enviados para estudo histológico. Resultados: O tempo de isquemia mostrou forte influência com a graduação histológica. Com 30 minutos de isquemia, nenhum comprimento de onda (408, 442 e 532 nm) apresentou correlação com a graduação histológica (p = 0,81; p = 0,11; p = 0,21, respectivamente). Com 60 minutos de isquemia, o laser de excitação de 532 nm (na fase de reperfusão) apresentou coeficiente de correlação negativa significativa (r = - 0,61) com a graduação histológica. Na isquemia de 120 minutos, o laser com 442 nm de comprimento de onda (na fase de reperfusão) mostrou o coeficiente de correlação negativa significativa (r = - 0,73) com a graduação histológica. O terço médio renal apresentou média estatística superior à dos polos (p < 0,001) na leitura da espectroscopia de fluorescência. Conclusões: Há correlação entre os dados da espectroscopia de fluorescência induzida pelo laser e as alterações histológicas na isquemia renal em ratos, sendo necessário, durante a investigação, analisar apenas o terço médio renal. / Introduction: Renal transplantation is widely recognized as the best form of treatment for patients who require renal replacement therapy. Often, the transplant team is faced with a difficult question, if organs from deceased marginal donors or non-heart beating donors are able to be transplanted. It is difficult to quantify the intensity of damage caused by ischemia in the graft to be used, especially if the donor had hemodynamic instability with a significant decrease of the tissue perfusion and an increased of the risk of diminishing the graft function which could affect adversely its survival. Thus it is justified to use the technique of laser-induced fluorescence spectroscopy, to assess the correlations between its results and the histological grade in experimental renal injury, since it is an objective, non-invasive, fast and in real-time analysis, which can be applied, in the future, in human kidney transplants. Objectives: To evaluate the correlation between the data of laser-induced fluorescence spectroscopy and histological changes in kidney ischemia and reperfusion in rats, and if there are significant differences of reading between the upper and lower poles and the middle area of such kidneys. Materials and Methods: We used 33 adults male rats (Rattus norvegicus) of Wistar strain, which after anesthetized, had their left kidney addressed. Initially such kidneys were submitted to detection of the fluorescence spectroscopy of the upper pole, lower pole and the middle area. Excitations were generated by lasers having wavelengths of 408, 442 and 532 nm. Then the left renal pedicles were dissected, isolated and clamped. Then the animals were randomized into three ischemic groups of 30, 60 and 120 minutes. In each group, the kidneys were analyzed by fluorescence spectroscopy for the second time, and again after 5 minutes of reperfusion, using excitatory beam with same wavelength, at the poles (upper and lower) and the middle area of the kidneys. Later, the left kidney were collected and sent for histological examination. Results: The ischemia time showed a strong influence on the histological grade. With 30 minutes of ischemia, no wavelength (408, 442 and 532 nm) was correlated with the histological lesions (p = 0.81, p = 0.11, p = 0.21, respectively). With 60 minutes of ischemia, the laser excitation of 532 nm (in the reperfusion phase) showed a significant negative correlation coefficient (r = - 0.61) with the histological grading. In 120 minutes of ischemia, laser with 442 nm wavelength (in the reperfusion phase) showed a significant negative correlation coefficient (r = - 0.73) with the histological grade. The middle area of the kidneys showed a higher average statistically (p< 0,001) than the poles in the reading of fluorescence spectroscopy. Conclusions: There is a strong correlation between the data of laser-induced fluorescence spectroscopy and the histological changes in rats renal ischemia, being necessary, during the investigation, to analyze only the middle area of the kidneys.

Introdução: O transplante renal é amplamente reconhecido como a melhor forma de tratamento para os pacientes que necessitam de terapia de substituição renal. Frequentemente a equipe transplantadora se depara com a difícil questão de determinar se órgãos, provenientes de doadores falecidos e limítrofes ou em parada cardíaca, estão aptos para serem transplantados. É difícil quantificar a intensidade do dano provocado pela isquemia no enxerto a ser utilizado, especialmente se o doador apresentou quadro de instabilidade hemodinâmica com queda significativa da perfusão tecidual e aumento do risco de diminuir a função do enxerto e afetar adversamente sua sobrevida. Desta forma torna-se justificável a utilização da técnica de espectroscopia de fluorescência induzida pelo laser, na tentativa de se avaliar a correlação entre os seus achados e o grau de lesão histológica renal experimental, uma vez que se trata de um método objetivo, não invasivo, rápido e em tempo real que, futuramente, pode ser aplicada nos transplantes renais em humanos. Objetivos: Avaliar a correlação entre os dados da espectroscopia de fluorescência induzida pelo laser e alterações histológicas na isquemia e reperfusão renal em ratos, e se existe diferença significativa na leitura da espectroscopia entre os polos superior, inferior e o terço médio. Materiais e Métodos: Foram utilizados 33 ratos (Rattus norvegicus) machos adultos da linhagem Wistar que, depois de anestesiados, tiveram seus rins esquerdos abordados. Inicialmente os rins foram submetidos à detecção da espectroscopia de fluorescência dos pólos superiores, inferiores e terços médios. As excitações foram geradas por lasers com comprimentos de onda de 408, 442 e 532 nm. Em seguida os pedículos renais esquerdos foram dissecados, isolados e clampeados com auxílio de mini-pinça vascular. Então, os animais foram divididos aleatoriamente em três grupos isquêmicos de 30, 60 e 120 minutos de isquemia quente. Em cada um dos grupos, os rins foram novamente analisados pela espectroscopia de fluorescência, bem como após 5 minutos de reperfusão, utilizando novamente feixes excitatórios com os mesmos comprimentos de onda, nas mesmas regiões renais. Posteriormente os rins esquerdos foram coletados e enviados para estudo histológico. Resultados: O tempo de isquemia mostrou forte influência com a graduação histológica. Com 30 minutos de isquemia, nenhum comprimento de onda (408, 442 e 532 nm) apresentou correlação com a graduação histológica (p = 0,81; p = 0,11; p = 0,21, respectivamente). Com 60 minutos de isquemia, o laser de excitação de 532 nm (na fase de reperfusão) apresentou coeficiente de correlação negativa significativa (r = - 0,61) com a graduação histológica. Na isquemia de 120 minutos, o laser com 442 nm de comprimento de onda (na fase de reperfusão) mostrou o coeficiente de correlação negativa significativa (r = - 0,73) com a graduação histológica. O terço médio renal apresentou média estatística superior à dos polos (p < 0,001) na leitura da espectroscopia de fluorescência. Conclusões: Há correlação entre os dados da espectroscopia de fluorescência induzida pelo laser e as alterações histológicas na isquemia renal em ratos, sendo necessário, durante a investigação, analisar apenas o terço médio renal. / Introduction: Renal transplantation is widely recognized as the best form of treatment for patients who require renal replacement therapy. Often, the transplant team is faced with a difficult question, if organs from deceased marginal donors or non-heart beating donors are able to be transplanted. It is difficult to quantify the intensity of damage caused by ischemia in the graft to be used, especially if the donor had hemodynamic instability with a significant decrease of the tissue perfusion and an increased of the risk of diminishing the graft function which could affect adversely its survival. Thus it is justified to use the technique of laser-induced fluorescence spectroscopy, to assess the correlations between its results and the histological grade in experimental renal injury, since it is an objective, non-invasive, fast and in real-time analysis, which can be applied, in the future, in human kidney transplants. Objectives: To evaluate the correlation between the data of laser-induced fluorescence spectroscopy and histological changes in kidney ischemia and reperfusion in rats, and if there are significant differences of reading between the upper and lower poles and the middle area of such kidneys. Materials and Methods: We used 33 adults male rats (Rattus norvegicus) of Wistar strain, which after anesthetized, had their left kidney addressed. Initially such kidneys were submitted to detection of the fluorescence spectroscopy of the upper pole, lower pole and the middle area. Excitations were generated by lasers having wavelengths of 408, 442 and 532 nm. Then the left renal pedicles were dissected, isolated and clamped. Then the animals were randomized into three ischemic groups of 30, 60 and 120 minutes. In each group, the kidneys were analyzed by fluorescence spectroscopy for the second time, and again after 5 minutes of reperfusion, using excitatory beam with same wavelength, at the poles (upper and lower) and the middle area of the kidneys. Later, the left kidney were collected and sent for histological examination. Results: The ischemia time showed a strong influence on the histological grade. With 30 minutes of ischemia, no wavelength (408, 442 and 532 nm) was correlated with the histological lesions (p = 0.81, p = 0.11, p = 0.21, respectively). With 60 minutes of ischemia, the laser excitation of 532 nm (in the reperfusion phase) showed a significant negative correlation coefficient (r = - 0.61) with the histological grading. In 120 minutes of ischemia, laser with 442 nm wavelength (in the reperfusion phase) showed a significant negative correlation coefficient (r = - 0.73) with the histological grade. The middle area of the kidneys showed a higher average statistically (p< 0,001) than the poles in the reading of fluorescence spectroscopy. Conclusions: There is a strong correlation between the data of laser-induced fluorescence spectroscopy and the histological changes in rats renal ischemia, being necessary, during the investigation, to analyze only the middle area of the kidneys.

Dissertation (MD)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: Acute renal failure still is, with the exception of cardiac deaths, the most important pathological process associated with perioperative mortality in patients operated for abdominal aortic aneurysms. The intraoperative change in renal blood flow (RBF) and glomerular function have been investigated in human and animal models, particularly over the past 15 years. Despite large variation in study populations, measurement techniques and study designs in general, a significant body of evidence has developed which suggests infrarenal aortic clamp-induced renal ischemia to be the cause of postoperative acute renal failure when this complication does occur. It is rather surprizing then that, despite some recent studies which have reported on various pharmacological interventions to prevent intraoperative renal ischemia (with variable success), very little has apparently been done to unravel the pathogenesis and exact pathophysiology of this potentially lethal complication. Although a number of investigators suggest the possibility of hormonal involvement (particularly reninangiotensin, antidiuretic hormone (ADH) and catecholamines) in the process, the exact role of these mediators have not been explored (or reported) in a structured fashion. In an initial human study, renal hemodynamics and function were measured from the preoperative period, during the intraoperative phase and at least until 4 hours after aortic unclamping. To investigate the possibility of a temporal relationship between renal changes and fluctuations in hormonal concentrations, plasma concentrations of relevant hormones were determined at every sampling period where renal parameters were measured. The decrease in RBF and glomerular filtration rate (GFR) which we demonstrated to coincide with infrarenal aortic cross clamping, is consistent with results previously published. We demonstrated persistence of the impairment of these parameters as long as 4 hours into the postoperative phase; which has previously only been reported for the period until immediately after aortic unclamping with the abdomen still open. The persistence of a depressed GFR until the time of discharge of patients is cause for concern, particularly in patients with compromised renal function prior to surgery. Of the measured hormones with a potential influence on RBF and nephron function, renin was the only mediator where changes in plasma concentrations coincided with the depression of RBF and GFR after aortic cross clamping. The design of our study did not allow us to conclude whether the concomitant increase in angiotensin II was primarily responsible for the change in renal hemodynamics, or whether the raised renin (and angiotensin) levels were stimulated by the decrease in RBF induced by another mechanism. In another patient group, we demonstrated that the combination of mannitol and dopamine provided no protection against the deleterious effects of aortic cross clamping. In fact, the high urine volumes produced under the influence of these agents (which did not correlate with RBF at the corresponding periods), is likely to prompt a false sense of security. Given the lack of any objective benefit afforded by these agents, their use in these clinical circumstances should be discouraged. The animal studies were aimed at elucidation of the exact role of angiotensin in the pathogenesis and pathophysiology of the renal changes associated with infrarenal aortic clamping, as well as the interaction of angiotensin with other modulators for which an interactive relationship had been described previously under other experimental and/or clinical circumstances. The first study showed that, although renin (and thus angiotensin) concentrations were high after aortic unclamping, the hormone had no pathogenic or pathophysiological role of significance in the observed renal changes during this period (since blocking angiotensin II activation by the prevention of renin release, or by inhibiting the conversion enzyme, did not prevent a substantial decrease in RBF or GFR during that period). Preventing angiotensin II activation did, however, prevent renal changes during aortic clamping. This beneficial effect did not establish a primary role for angiotensin during that period, since the favourable influence could also (at least partially) be explained by prevention of the permissive influence of angiotensin on other vasoconstrictors and/or other vasodilatory influences of ACE inhibition and [1- blockade which are unrelated to angiotensin. This study did indicate that (at least partially) different mechanisms are responsible for the renal changes seen during aortic clamping, and after aortic unclamping. The second study explored the role of calcium in the renal pathophysiological changes during aortic clamping and after unclamping. The protective influence effected by the administration of a Ca2 + -blocker suggest the dependence of the renal vasoconstrictive and glomerular pathophysiological process( es) on the cellular influx of Ca2 + through voltage-gated channels. It unfortunately provides no definitive insight into the primary instigators of these processes. However, it does offer a clinically useful method of preventing these changes and protecting the kidney against ischemic injury during abdominal aortic surgery. The third component of the animal studies demonstrates the importance of the protective effect of renal prostaglandins during the specific experimental (and probably also the clinical) circumstances. Again, it does not provide definitive information on the mediators responsible for the renal changes, since the deleterious effects of numerous endogenous substances have previously been shown to be counterbalanced by intrarenal synthesis of prostaglandins under various experimental and clinical circumstances. The extent of the pathophysiological and ultrastructural changes which occurred under the influence of a NSAID does, however, suggest that these drugs should not be used under these clinical circumstances. The last component of the study provides evidence that angiotensin only plays a secondary/supplementary role in the renal pathophysiological process even during aortic clamping. This may explain the contradictory evidence regarding the potential beneficial effect of ACE inhibition (on renal hemodynamics and glomerular function) during abdominal aortic surgery (Licker et al. 1996, Colson et al. 1992a). Based on our studies, ACE inhibition can not be supported for this purpose. / AFRIKAANSE OPSOMMING: Akute nierversaking is met die uitsondering van kardiale sterftes, steeds die belangrikste patologiese proses wat geassosieer is met perioperatiewe mortaliteit in pasiënte wat opereer word vir abdominale aorta aneurismes. Die intraoperatiewe veranderinge in renale bloedvloei (NBV) en glomerulêre funksie is die afgelope 15 jaar ondersoek en gerapporteer in pasiënte- sowel as diere-modelle. Ten spyte van groot variasies in studie-populasies, meettegnieke en ontwerp van studies in die algemeen, dui 'n wesenlike hoeveelheid getuienis daarop dat infrarenale klemming van die aorta renale isgemie induseer, wat die oorsaak is van postoperatiewe akute nierversaking wanneer hierdie komplikasie voorkom. Dit is verbasend dat, ten spyte van sommige onlangse studies wat rapporteer oor 'n verskeidenheid farmakologiese ingrepe om intraoperatiewe renale isgemie te voorkom (met wisselende sukses), baie min oënskynlik gedoen is om die patogenese en die presiese patofisiologie van hierdie potensieel dodelike komplikasie te ontrafel. Hoewel verskeie outeurs die moontlikheid van hormonale betrokkenheid (veral renienangiotensien, antidiuretiese hormoon en katekolamiene) in hierdie proses suggereer, is die presiese rol van hierdie mediators nog nie op 'n gestruktureerde wyse ondersoek (of rapporteer) nie. In ons aanvanklike pasiënte-studie is renale hemodinamika en -funksie gemeet vanaf die preoperatiewe periode, gedurende die intra-operatiewe fase en tot minstens vier uur na ontklemming van die aorta. Serumkonsentrasies van relevante hormone is bepaal tydens elke metingsperiode waar renale parameters gemeet is, ten einde die moontlikheid van 'n temporale verwantskap tussen renale veranderinge en variasies in hormoonkonsentrasies te ondersoek. Die vermindering in NBV en glomerulêre filtrasiespoed (GFS) wat ons aangetoon het om saam te val met infrarenale aortaklemming, stem ooreen met resultate wat tevore deur ander navorsers publiseer is. Ons het aangetoon dat die inkorting van hierdie parameters voortduur tot minstens vier uur na aorta-ontklemming. Hierdie veranderinge is tevore slegs rapporteer vir periodes tot kort na aorta-ontklemming voor sluiting van die buikwond. Die feit dat die GFS steeds verlaag is met ontslag van hierdie pasiënte, skep rede tot kommer, veral in pasiënte wat alreeds ingekorte nierfunksie het voor die chirurgiese prosedure. Van die gemete hormone wat moontlik 'n invloed sou kon uitoefen op NBV eh nefronfunksie, was renien die enigste waarvan verandering in plasmakonsentrasies saamgeval het met die onderdrukking van NBV en GFS na aortaklemming. Die ontwerp van ons studie het ons nie toegelaat om 'n besliste uitspraak te maak of die geassosieerde verhoging in angiotensien II primêr verantwoordelik was vir die verandering in renale hemodinamika, of dat die verhoogde renien (en angiotensien) bloedvlakke moontlik sekondêr stimuleer is deur die verandering in NBV wat deur 'n ander meganisme induseer is. In 'n ander pasiëntegroep het ons aangetoon dat die kombinasie van mannitol en dopamien geen beskerming verleen het teen die nadelige effekte van aorta-klemming nie. Die groot volumes uriene wat uitgeskei is onder die invloed van hierdie middels (wat nie korreleer het met NBV tydens ooreenstemmende periodes nie), het inderwaarheid 'n ontoepaslike gerustheid uitgelok. Weens die ooglopende gebrek aan objektiewe voordeel wat verleen word deur hierdie middels, behoort hulle gebruik tydens hierdie kliniese omstandighede ontmoedig te word. Die doel van die diere studies was die identifisering van die presiese rol van angiotensien in die patogenese en patofisiologie van die renale veranderinge geassosieer met infrarenale aortaklemming, sowel as die interaksie van angiotensien met ander modulators waarvoor 'n interaktiewe verwantskap voorheen beskryf is onder eksperimentele en/of kliniese omstandighede. Die eerste studie het getoon dat alhoewel renien (en dus angiotensien) konsentrasies hoog was na aorta-ontklemming, die hormone geen betekenisvolle patogenetiese of patofisiologiese rol in die waargenome renale veranderinge gedurende hierdie periode het nie (aangesien blokkade van angiotensien aktivering deur voorkoming van renien vrystelling, of deur inhibisie van angiotensien omsettingsensiem (AOE), nie 'n daling in NBV of GFS kon voorkom nie). Voorkoming van angiotensien II aktivering het egter wel renale verandering voorkom gedurende aortaklemming. Dié voordelige effek het nie 'n primêre rol vir angiotensien gedurende die periode bevestig nie, aangesien die gunstige invloed ook (ten minste gedeeltelik) verduidelik kon word deur die voorkoming van die fassiliterende invloed van angiotensien op ander vasokonstriktore en/of ander vasodilator-invloede van die onderdrukking van AOE en ïs-blokkers (wat geen verband het met angiotensien of die blokkade daarvan nie). Die studie het aangetoon dat (ten minste gedeeltelik) verskillende meganismes verantwoordelik is vir renale veranderinge wat gesien is gedurende aortaklemming en na -ontklemming. Die tweede studie het die rol van kalsium in die renale patofisiologiese veranderinge gedurende aortaklemming en na ontklemming ondersoek. Die beskermende invloed wat deur die toediening van Ca2 + -blokkers bewerkstellig is, het bevestig dat die renale vasokonstriktoriese en glomerulêre patofisiologiese prosesse afhanklik is van sellulêre influks van kalsium deur spannings-afhanklike kannale. Dit het ongelukkig geen definitiewe insig verleen ten opsigte van die primêre inisieerders van die proses nie. Dit verskaf nogtans 'n bruikbare kliniese metode om daardie veranderinge te voorkom en die niere teen isgemiese besering gedurende abdominale aorta-chirurgie te beskerm. Die derde komponent van die diere-studies demonstreer die belangrikheid van die beskermende effek van renale prostaglandiene tydens die spesifieke eksperimentele (en waarskynlik ook die kliniese) omstandighede. Weereens gee dit nie definitiewe inligting oor die bemiddelaars wat verantwoordelik is vir die renale veranderinge nie, aangesien die skadelike effekte van verskeie endogene stowwe voorheen aangetoon is om beperk of voorkom te word deur die intrarenale vrystelling van prostaglandiene. Die omvang van die patofisiologiese en ultrastrukturele veranderinge wat ontstaan het onder die invloed van nie-steroïed anti-inflammatoriese middels (wat gebruik is om prostaglandien sintese te inhibeer), dui aan dat hierdie middels vermy moet word onder soortelyke kliniese omstandighede. Die laaste komponent van die studie verskaf 'n sterk aanduiding dat angiotensien slegs 'n sekondêre/aanvullende rol speel in die renale patofisiologiese proses, selfs gedurende aortaklemming. Dit mag die weersprekende getuienis oor die potensiële voordeel van AOE onderdrukking (op renale hemodinamika en glomerulêre funksie) gedurende abdominale aortachirurgie (Licker et al. 1996, Colson et al. 1992a) verklaar. Gebaseer op ons studies, kan AOE onderdrukking nie ondersteun word vir hierdie doel nie.

Le syndrome d'ischémie-reperfusion (IR), inhérent à la transplantation rénale, est caractérisé par un infiltrat leucocytaire important et des lésions tissulaires graves dont les signaux initiateurs restent à ce jour peu décrits. Postulant que la libération d'alarmines par les cellules en nécrose est décisive dans ce processus, l'objectif principal du présent travail a été d'étudier la contribution de l'alarmine IL-33 dans la genèse des lésions tissulaires dans un modèle murin d'IR rénale. Nos résultats montrent que l'IL-33 est rapidement libérée du rein après IR comme protéine circulante, dès une heure de reperfusion. Les souris IL-33gt/gt, déficientes en IL-33, sont moins sensibles aux lésions induites par l’IR, comme l'attestent le maintien de la fonction rénale et des lésions histologiques atténuées avec un recrutement de polynucléaires neutrophiles (PNN) diminué par rapport aux souris contrôles. Ceci est associé à la perte du recrutement de cellules iNKT productrices d'IFN-γ/IL-17A. Parallèlement, les souris Jα18KO, déficientes en cellules iNKT et protégées contre les lésions d'IR, possèdent également des niveaux élevés d'IL-33 circulante. Nous proposons donc que l'IL-33 endogène contribue aux lésions d'IR en favorisant le recrutement de cellules iNKT, conduisant ainsi à un recrutement amplifié de PNN au niveau du rein lésé. Notre étude, en identifiant l'alarmine IL-33 comme un médiateur précoce de la réponse immunitaire innée induite par l'IR rénale, mettant en jeu les cellules iNKT, contribue à la compréhension des mécanismes impliqués dans la genèse des lésions associées à la greffe rénale et permet de proposer de nouvelles stratégies thérapeutiques. / Ischemia-reperfusion (IR) injury in renal transplantation is characterized by leukocyte infiltration and tissue damage. However, the signals that initiate these events remain poorly understood. Assuming that alarmin release by necrotic cells during IRI is critical, the main objective of the present study was to investigate the role of alarmin IL-33 in kidney injury using a mouse model of renal IR. We observed release of IL-33 shortly after kidney IR concomitantly with an increase in plasma levels of IL-33 within one hour of reperfusion. IL-33 deficient mice (IL-33gt/gt) exhibited reduced renal IR-induced injury, as attested by function preservation, reduced histological change and attenuation of neutrophil recruitment compared to control mice. This was associated with the loss of IFN-γ/IL-17A-producing iNKT cell recruitment. In the meantime, iNKT cell-deficient (Jα18KO) mice, also protected against IRI, have increased levels of circulating IL-33.These findings lead us to propose that endogenous IL-33 contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, thereby promoting amplified neutrophil recruitment to the injured kidney. The present study identifies the nuclear alarmin interleukin (IL)-33 as an important and early mediator of innate immune response, involving iNKT cells, following experimental kidney ischemia-reperfusion in mice. Our findings contribute to a better understanding of IR-induced injury and may lead to new therapeutic insights into renal-induced injury associated with renal transplantation.