Mouse Model Of Renal Ischemia-reperfusion Injury Research Articles

Renal Ischemia-reperfusion Injury Attenuated by Exosomes Extracted From Splenic Ischemic Preconditioning Models.

To investigate the protective effects of exosomes extracted from splenic ischemic preconditioning (sIPC) models on renal ischemia-reperfusion injury (IRI). sIPC was conducted on mice before renal IRI, and exosomes derived from sIPC mice were infused into a mouse model of renal IRI. The kidney tissue and serum were collected 24 h later. The morphological changes, inflammation and apoptosis in IR kidneys were determined by hematoxylin-eosin (HE), terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and Ki-67 immunohistochemical staining. In addition, the proinflammatory cytokines in serum and cell supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). Then, we administered exosomes to mouse renal epithelial cells. TUNEL assays and flow cytometry were used to evaluate cell apoptosis. Bax and Bcl-2 levels were measured via Western blotting. HE staining showed that the renal IRI was attenuated after sIPC. TUNEL results showed that renal tissue apoptosis was greatly reduced after sIPC or injection of exosomes. ELISAs showed that the serum creatinine (sCr), tumor necrosis factor alpha, and interleukin-1 β levels induced by IRI decreased with sIPC. In vitro, exosomes extracted from the hypoxia/reoxygenation (H/R) splenic fibroblast model had the same protective effect. TUNEL and flow cytometry results showed that the exosomes reduced apoptosis. ELISAs showed that tumor necrosis factor alpha and interleukin-1 β were significantly increased in the H/R group but decreased due to the exosomes treated with starvation. WB results showed that Bax expression was increased and Bcl-2 expression was decreased in the H/R group. However, exosomes decreased the Bax level and increased the Bcl-2 level. Exosomes extracted from sIPC models exerted a protective effect to attenuate renal IRI.

MiR-181d-5p Targets KLF6 to Improve Ischemia/Reperfusion-Induced AKI Through Effects on Renal Function, Apoptosis, and Inflammation.

Renal tubular epithelial cell (RTEC) death and renal interstitial inflammation are the most crucial pathophysiological changes in acute kidney ischemia/reperfusion injury (IRI). The microRNA (miR)-181d family plays diverse roles in cell proliferation, apoptosis and inflammation, but its renal target and potential role in IRI are unknown. Here, we showed that the expression of miR-181d-5p decreased and Krueppel-like factor 6 (KLF6) increased in a renal cell (HK-2) model of hypoxia/reoxygenation (H/R) injury and a mouse model of renal IRI. They were mainly distributed in the renal tubules. After renal IRI, miR-181d-5p overexpression significantly inhibited inflammatory mediators, reduced apoptosis and further improved renal function. KLF6 exacerbated RTEC damage and acted as a NF-κB co-activator to aggravate the renal IRI inflammatory response. Mechanistically, KLF6 was predicted as a new potential target gene of miR-181d-5p through bioinformatic analysis and luciferase reporter assay verification. After overexpressing miR-181d-5p and inhibiting KLF6, the role of miR-181d-5p was weakened on the renal damage improvement. In conclusion, miR-181d-5p upregulation produced protective antiapoptotic and anti-inflammatory effects against IRI in kidneys in vivo and H/R injury in HK-2 cells in vitro, and these effects were achieved by targeted inhibition of KLF6. Thus, our results provide novel insights into the molecular mechanisms associated with IRI and a potential novel therapeutic target.

Evaluation of Glutaredoxin 1 as a Novel Marker of Renal Damage after Ischemia‐Reperfusion Injury in Mice

Renal ischemia‐reperfusion injury (IRI) is a significant cause of acute renal failure and delayed graft function in clinical patients. Tissue damage in renal IRI is caused in part by the activation of the immune response and the generation of reactive oxygen species (ROS), both taking place mainly during the reperfusion phase, once the blood supply to the tissue is restored. Glutaredoxin 1 (Grx1), a cytosolic protein that reduces protein disulfides as well as glutathionylated proteins, plays a protective role in ROS‐mediated damage to the cell. In a previous work, we detected increased levels of Grx1 in the urine of mice 24h after renal IRI 1. Recently, Grx1 was shown to be elevated in the serum of patients with chronic kidney disease 2. To determine the usefulness of Grx1 as a possible biomarker of ischemic renal damage we evaluated serum, urinary, as well as intra‐renal levels of Grx1 in a mouse model of renal IRI. Different reperfusion times (4h, 8h, 16h, 24h, 48h, 96h, and 168h) were compared in order to follow Grx1 fluctuation levels in the kidney, serum, and urine. Serum Grx1 levels, analyzed by ELISA, were correlated with several renal function parameters such as serum creatinine, proteinuria, glomerular diameter, and tubular thickness. After IRI, Grx1 serum levels increased much earlier than creatinine (4h versus 24h). Western blot analyses showed a decrease of Grx1 in the kidney of mice with surgically induced IRI, compared to the sham group. Additionally, immunohistochemistry revealed an increased apical localization of Grx1 in cells of the distal convoluted tubules of the mice exhibiting IRI. Urinary levels of Grx1, even if increased in the first hours after renal IRI, were not significantly altered. These findings provide initial supporting evidence for the use of a redox protein such as Grx1 as a novel biomarker for assessing renal damage under experimental conditions. Further studies are necessary to validate these results.Support or Funding InformationThis work was funded by the Center of Integrative Mammalian Research of Ross University School of Veterinary Medicine.

Isoquercitrin Attenuates Renal Ischemia/Reperfusion Injury Through Antioxidation, Anti-inflammation, and Antiapoptosis in Mice

Renal ischemia-reperfusion injury (RIRI) occurs after several surgical procedures such as kidney transplantation and partial nephrectomy. Isoquercitrin (IQ) exhibited protective effects in cerebral ischemia-reperfusion injury. In the present study, we aimed to evaluate the effects of IQ on the prevention of RIRI. The mouse model of RIRI was induced by 30-minute clamping of the left renal pedicle after excising of the right kidney, followed by 24-hour reperfusion. Thirty mice were randomly divided into the following 3 groups: sham operation, RIRI model group, and IQ pretreatment + RIRI. Serum creatinine and blood urea nitrogen (BUN) were used for evaluating renal function. Kidney cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Moreover, the pro-inflammatory cytokines (TNF-α, IL-6), the oxidative stress associated factors (malondialdehyde, superoxide dismutase), and the apoptotic factors (Bcl-2, Bax) were assessed. After RIRI, BUN, creatinine, TNF-α, IL-6, malondialdehyde, and Bax were significantly increased, and levels of superoxide dismutase and Bcl-2/Bax ratio and Bcl-2 expression were decreased markedly. As expect, IQ reversed these changes. These data indicate that IQ plays a protective role during RIRI, which may be partially mediated through the actions of antioxidation, anti-inflammation, and antiapoptosis.

A mouse model of renal ischemia-reperfusion injury solely induced by cold ischemia.

Transplanted kidneys usually experience several episodes of ischemia, including cold ischemia during allograft storage in preservation solution. However, previous studies focusing on cold renal ischemia were only carried out in vitro or ex vivo. In the present study, we developed and characterized an in vivo mouse model of renal ischemia-reperfusion injury (IRI) induced exclusively by cold ischemia. C57BL/6 mice underwent right kidney nephrectomy, and the left kidney was kept cool with circulating cold saline in a kidney cup, while body temperature was maintained at 37°C. We clamped the renal pedicle and flushed out the blood inside the kidney with cold saline via an opening on the renal vein. The severity of renal IRI was examined with different ischemic durations. We found that the mice with <2 h of cold ischemia exhibited no significant changes in renal function or histopathology; animals with 3 or 4 h of cold ischemia developed into mild to moderate acute kidney injury with characteristic features, including the elevation in plasma creatinine concentration and reduction in glomerular filtration rate and tubular necrosis, followed by a subsequent recovery. However, mice with 5 h of cold ischemia died in a few days with severe acute kidney injury. In summary, we generated a mouse model of renal IRI induced exclusively by cold ischemia, which mimics graft cold storage in preservation solution, and renal function can be evaluated in vivo.

Complement-mediated Damage to the Glycocalyx Plays a Role in Renal Ischemia-reperfusion Injury in Mice.

BackgroundComplement activation plays an important role in the pathogenesis of renal ischemia-reperfusion (IR) injury (IRI), but whether this involves damage to the vasculoprotective endothelial glycocalyx is not clear. We investigated the impact of complement activation on glycocalyx integrity and renal dysfunction in a mouse model of renal IRI.MethodsRight nephrectomized male C57BL/6 mice were subjected to 22 minutes left renal ischemia and sacrificed 24 hours after reperfusion to analyze renal function, complement activation, glycocalyx damage, endothelial cell activation, inflammation, and infiltration of neutrophils and macrophages.ResultsIschemia-reperfusion induced severe renal injury, manifested by significantly increased serum creatinine and urea, complement activation and deposition, loss of glycocalyx, endothelial activation, inflammation, and innate cell infiltration. Treatment with the anti-C5 antibody BB5.1 protected against IRI as indicated by significantly lower serum creatinine (P = 0.04) and urea (P = 0.003), tissue C3b/c and C9 deposition (both P = 0.004), plasma C3b (P = 0.001) and C5a (P = 0.006), endothelial vascular cell adhesion molecule-1 expression (P = 0.003), glycocalyx shedding (tissue heparan sulfate [P = 0.001], plasma syndecan-1 [P = 0.007], and hyaluronan [P = 0.02]), inflammation (high mobility group box-1 [P = 0.0003]), and tissue neutrophil (P = 0.0009) and macrophage (P = 0.004) infiltration.ConclusionsTogether, our data confirm that the terminal pathway of complement activation plays a key role in renal IRI and demonstrate that the mechanism of injury involves shedding of the glycocalyx.

Blockade of the G-CSF Receptor is Protective in a Mouse Model of Renal Ischemia Reperfusion Injury

Background Ischemia-reperfusion injury (IRI) is a complex inflammatory process that detrimentally affects the function of transplanted organs. Several pathways contribute to cell death and microvascular dysfunction in IRI, including activation of the innate and adaptive arms of the immune system. Inhibiting complement, a key component of innate immunity, by C5 blockade has been shown to protect against renal IRI in mice. In this study, we investigated whether targeting neutrophils with VR81, a monoclonal antibody recognising the granulocyte colony stimulating factor receptor (G-CSFR), would reduce inflammation and protect against injury in a mouse model of renal IRI. The anti-C5 antibody BB5.1 was used for comparison. Methods Male 10-12 week old C57BL/6 mice underwent right nephrectomy followed by clamping of the left renal pedicle for 22 min, or right nephrectomy only (Sham), at 37°C. Mice (n = 5-8 per group) were injected i.p. at 24 hr pre-ischemia with VR81 (100, 200 or 500 μg), BB5.1 (100 μg), or isotype-matched antibody (Ab) control (500 μg). Mice were euthanased 24 hr after reperfusion, and serum and plasma samples were collected to assess renal function (creatinine, urea) and complement activation (C5a ELISA). Kidneys were harvested to analyse complement C9 deposition and immune cell infiltration by immunofluorescence. Results Compared to Sham, the Ab control IRI group showed significantly increased creatinine, urea and C5a, deposition of C9, and infiltration of neutrophils and macrophages. As expected, C5 blockade with BB5.1 markedly reduced renal injury and inflammation, reflected in significantly lower creatinine, urea, C5a and C9 deposition versus Ab control. Surprisingly, VR81 was also strongly protective in a dose-dependent manner, with the 500 μg dose significantly reducing creatinine, urea and cellular infiltration. Conclusion Unexpectedly, G-CSFR blockade using VR81 significantly protected against renal IRI with an efficacy similar to that of anti-C5 treatment. Protection was associated with markedly reduced infiltration by neutrophils and macrophages. G-CSFR blockade is thus a promising new approach to reduce IRI and improve organ transplant function.

Extract of Rhus verniciflua stokes protects against renal ischemia-reperfusion injury by enhancing Nrf2-mediated induction of antioxidant enzymes.

Ischemia-reperfusion injury (IRI) may cause acute kidney disease (AKD) by mediating the oxidative stress-induced apoptosis of parenchymal cells. The extract of Rhus verniciflua Stokes (RVS) is used as a traditional herbal medicine as it exhibits anti-oxidant, anti-apoptotic and anti-inflammatory properties. Therefore, the current study investigated the therapeutic effect and the underlying mechanism of RVS on IRI-induced AKD in vivo and in vitro. The current study assessed the effects of RVS on a mouse model of renal IRI and in hypoxic human renal tubular epithelial HK-2 cells. The results demonstrated that the IRI-induced elevation of blood urea nitrogen, serum creatinine and lactate dehydrogenase was significantly attenuated by the intraoral administration of RVS (20 mg/kg/day) for 14 days prior to surgery. It was demonstrated that IRI surgery induced histological damage and cellular apoptosis in renal parenchyma, which were attenuated by pretreatment with RVS. Furthermore, in HK-2 cells incubated with 300 µM CoCl2 to induce chemical hypoxia, it was demonstrated that RVS treatment significantly inhibited cell death and the production of reactive oxygen species (ROS). Furthermore, RVS treatment upregulated the levels of endogenous antioxidant enzymes, including heme oxygenase-1 and catalase, as well as their upstream regulator nuclear factor erythroid 2-related factor 2, in HK-2 cells. Taken together, these results suggested that the intraoral administration of RVS induces a therapeutic effect on IRI-induced AKD. These effects are at least partly due to the attenuation of ROS production via upregulation of the antioxidant defense system in renal tubular cells.

Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury.

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33-treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo-expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo-expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33-ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.

Changes in APPL1 expression during renal fibrosis in a mouse model of renal ischemia-reperfusion injury

Objective To evaluate the changes in the expression of adaptor protein containing pleckstrin homobgy domain, phosphotyrosine-binding domain and a leucine zipper motif 1(APPL1)during renal fibrosis in a mouse model of renal ischemia-reperfusion(I/R)injury. Methods Twenty-four male C57BL/6 mice, aged 8 weeks, weighing 20-25 g, were divided into 2 groups(n=12 each)using a random number table: sham operation group(S group)and renal I/R group.The model of renal I/R injury was established by clipping the bilateral renal pedicles for 30 min followed by reperfusion in group I/R.Six mice were selected at 2 days of reperfusion, and venous blood samples were collected for determination of serum concentrations of blood urea nitrogen and creatinine.The animals were then sacrificed, the renal specimens were obtained for microscopic examination of tubular necrosis with a light microscope, and the damage to the renal tubules was scored using a semi-quantitative method.Six mice were sacrificed at 14 days of reperfusion, and the renal specimens were obtained for assessment of the degree of renal fibrosis(using picric acid-sirius red staining)and for determination of the expression of collagen type 1, fibronectin and α-smooth muscle actin in renal tissues(by Western blot or immunofluorescence method). At 2 and 14 days of reperfusion, the expression of APPL1 in renal tissues was detected by Western blot and the expression of APPL1 mRNA in renal tissues by real-time polymerase chain reaction. Results Compared with group S, the serum concentrations of blood urea nitrogen and creatinine, scores of renal tubular damage and degree of renal fibrosis were significantly increased at 2 days of reperfusion, the expression of collagen type 1, fibronectin and α-smooth muscle actin in renal tissues was up-regulated at 14 days of reperfusion, and the expression of APPL1 protein and mRNA was up-regulated at 2 and 14 days of reperfusion in group I/R(P<0.05). Conclusion Up-regulated expression of APPL1 may be involved in the process of renal fibrosis in a mouse model of renal I/R injury. Key words: Fibrosis; Kidney; Ischemia-reperfusion; Adaptor proteins, signal transducing

Overexpression of Human CD55 and CD59 or Treatment with Human CD55 Protects against Renal Ischemia-Reperfusion Injury in Mice.

Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of increasing CD55 and CD59 activity has not been examined. In this study, we investigated the impact of overexpression of human (h) CD55 ± hCD59 or treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm renal ischemia, and analyzed 24 h after reperfusion for renal function (serum creatinine and urea), complement deposition (C3b/c and C9), and infiltration of neutrophils and macrophages. Transgenic mice expressing hCD55 alone were protected against mild renal IRI, with reduced creatinine and urea levels compared with wild type littermates. However, the renal function of the hCD55 mice was not preserved in the moderate IRI model, despite a reduction in C3b/c and C9 deposition and innate cell infiltration. Mice expressing both hCD55 and hCD59, on the other hand, were protected in the moderate IRI model, with significant reductions in all parameters measured. Wild type mice treated with rhCD55 immediately after reperfusion were also protected in the moderate IRI model. Thus, manipulation of CD55 activity to increase inhibition of the C3 and C5 convertases is protective against renal IRI, and the additional expression of hCD59, which regulates the terminal complement pathway, provides further protection. Therefore, anti-complement therapy using complement regulatory proteins may provide a potential clinical option for preventing tissue and organ damage in renal IRI.

Protection against ischemia/reperfusion‑induced renal injury by co‑treatment with erythropoietin and sodium selenite.

Ischemia/reperfusion injury (IRI) has lzong been an area of concern and focus of investigations. Erythropoietin (EPO) exhibits multiple protective effects, and selenium is an antioxidant trace element in the body, however, there have been no reports concerning the effects of EPO combined with sodium selenite on IRI. In the present study, a mouse model of renal IRI (RIRI) was pre–treated with EPO and sodium selenite to determine the most appropriate combination ratio of the two for further investigation. The results revealed that EPO and sodium selenite had synergistic protective effects in RIRI. EPO was identified as the predominant treatment component, with sodium selenite serving as an adjuvant, and combination treatment was markedly more effective, compared with treatment with either drug alone. The optimal ratio of treatment was 10:1 (10 IU EPO: 1 µg sodium selenite). The results indicated that RIRI markedly induced renal injury, as evidenced by elevated levels of blood urea nitrogen (BUN), as well as higher pathological scores, based on hematoxylin and eosin staining. Pre–treatment with EPO and sodium selenite significantly decreased serum expression levels of BUN and malonaldehyde, and increased the expression levels of superoxide dismutase, glutathione peroxidase and nitric oxide (NO), compared with the model group. Furthermore, co treatment with EPO and sodium selenite upregulated the protein expression levels of phosphatidylinositol 3 kinase (PI3K) in renal tissue samples. Together, the results suggested that co administration of EPO and sodium selenite effectively ameliorates IRI induced renal injury by reducing oxidative stress and activating the PI3K/NO signaling pathway.

Expression of Transforming Growth Factor-β1 Limits Renal Ischemia-Reperfusion Injury

Renal ischemia-reperfusion injury (IRI) largely contributes to kidney transplant dysfunction and acute kidney injury, but its pathogenesis is not fully understood. In this study, the role of transforming growth factor (TGF)-beta1 in renal IRI is investigated using TGF-beta1 deficient mice. Human renal tubular epithelial cells (TEC) line (HK-2) was used as an in vitro model, and cell apoptosis was determined by flow cytometric analysis. Renal IRI was induced in mice by clamping renal vein and artery for 45 min at 32 degrees C. Here, we showed that in cultures of HK-2 cells, TGF-beta1 expression was up-regulated by tumor necrosis factor (TNF)-alpha. Neutralization of TGF-beta1 activity increased both spontaneous and TNF-alpha-mediated apoptosis, and knockdown of TGF-beta1 expression increased the sensitivity of cell apoptosis to TNF-alpha. In a mouse model of renal IRI, a deficiency in TGF-beta1 expression increased the severity of renal injury, as indicated by more severe renal tubular damage, higher levels of serum creatinine or blood urea nitrogen in TGF-beta1 deficient mice as compared with those in wild-type controls. Further experiments showed that the antiapoptosis of TGF-beta1 correlated with up-regulation of Bcl-2 in kidney cells. Expression of TGF-beta1 in TECs, potentially induced by proinflammatory TNF-alpha, renders TECs resistance to cell death. In mice, TGF-beta1 deficiency results in more prone to IRI. These data imply that TGF-beta1 may act as a feedback survival factor in the resistance to kidney injury and maintenance of epithelium homeostasis.

Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury

Renal ischemia-reperfusion injury (IRI) is the leading cause of acute kidney injury [AKI; acute renal failure (ARF)] in native kidneys and delayed graft function in deceased donor kidney transplants. Serum creatinine rises late after renal IRI, which results in delayed diagnosis. There is an important need to identify novel biomarkers for early diagnosis and prognosis in renal IRI. Given the inflammatory pathophysiology of renal IRI, we used a protein array to measure 18 cytokines and chemokines in a mouse model of renal IRI at 3, 24, and 72 h postischemia. A rise in renal keratinocyte-derived chemokine (KC) was the earliest and most consistent compared with other molecules, with 3-h postischemia values being 9- and 13-fold greater than sham and normal animals, respectively. Histological changes were evident within 1 h of IRI but serum creatinine only increased 24 h after IRI. With the use of an ELISA, KC levels in serum and urine were highest 3 h postischemia, well before a significant rise in serum creatinine. The human analog of KC, Gro-alpha, was markedly elevated in urine from humans who received deceased donor kidney transplants that required dialysis, compared with deceased donor kidney recipients with good graft function and live donor recipients with minimal ischemia. Measurement of KC and its human analog, Gro-alpha, could serve as a useful new biomarker for ischemic ARF.

Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice.

Mononuclear cell infiltrates are found in human renal ischemia-reperfusion injury (IRI), and peritubular T lymphocytes have been identified in experimental IRI. However, the role of T cells in the pathogenesis of renal IRI is unknown. We hypothesized that T cells are one of the important mediators of renal IRI. To test this hypothesis, we used an established mouse model of renal IRI, and evaluated mice with genetically engineered deficiency of both CD4+ and CD8+ T cells. At 48 h postischemia, CD4/CD8-knockout (KO) mice had marked improvement in renal function compared with control C57BL/6 mice (serum creatinine: 0.7 +/- 0.4 vs. 2.5 +/- 0.3 mg/dl, respectively; P < 0.05). Neutrophil infiltration into postischemic kidney was reduced in CD4/CD8 KO mice, compared with control mice, at both 24 h [polymorphonuclear neutrophils (PMNs)/10 high power fields: 714 +/- 354 vs. 3,514 +/- 660, respectively; P < 0.05] and 48 h (88 +/- 32 vs. 1,979 +/- 209, respectively; P < 0.05). Tubular necrosis score in CD4/CD8 KO mice, compared with control mice, was significantly less at 48 h (0.4 +/- 0.1 vs. 2.4 +/- 0.2, respectively; P < 0.05). Because adhesion between T cells and renal tubular epithelial cells (RTECs) may underlie the pathophysiological role of T cells in renal IRI, we also measured T cell adhesion to primary murine RTECs in vitro. Exposure of RTECs to 2 h of hypoxia followed by 1 h of reoxygenation increased T cell adhesion more than twofold. Phorbol ester treatment, which activates integrins, increased T cell adhesion threefold. These data suggest that T lymphocytes can mediate experimental renal IRI. Moreover, adhesion of infiltrating T cells to renal tubular cells may provide a potential mechanism underlying postischemic tubular dysfunction.