Expression of Kidney Injury Molecule-1 in Healthy and Diseased Feline Kidney Tissue

Bland, S Karlyn; Schmiedt, Chad W.; Clark, Mary E.; Delay, J; Bienzle, Dorothee

doi:10.1177/0300985817690213

Cited by 26 publications

(33 citation statements)

References 76 publications

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“…This corresponds with another study in feline kidneys with natural and experimental AKI where kidney injury molecule 1 was shown to be most highly expressed in the S3 segment of the proximal tubule. 7 In the cats of the present study, the CMJ had significantly more mononuclear inflammatory cells, necrotic tubules, and mitotic figures during regeneration. This is further emphasized by the significantly greater amount of SMA and IC staining in the CMJ compared with the cortex and medulla.…”

Section: Discussionmentioning

confidence: 44%

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats

et al. 2015

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The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease.

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Section: Discussionmentioning

confidence: 44%

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats

et al. 2015

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“…Kidney fibrosis, a condition that causes impaired renal function, was increased in the DR+NF group but not in the HFD group. In an earlier literature review, uKIM-1 level correlated with the severity of renal histological damage, and can be a potential reliable predictor of adverse renal outcomes in acute tubular injury [ 25 ], and KIM-1 is a sensitive tissue indicator of AKI [ 26 ]. TNF-α, which causes inflammatory cell injury, can significantly induce the expression of the apo-A4 protein, which is also associated with pro-inflammatory acute kidney injury in human kidney cells [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study

Lin

Wang

et al. 2020

IJMS

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Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1/2 in proximal tubular cells by inhibiting the Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague–Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-α, CD36, SREBP-1/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups (p < 0.05). Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p < 0.05). Thus, NF may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.

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“…Vimentin was absent in the proximal tubules of healthy cats but expressed in injured S3. These findings indicate that S3 is the proximal tubular segment most susceptible to ischemic injury and that KIM-1 is a sensitive tissue indicator of AKI in cats [24]. The upregulation of KIM-1 at 24 h with rapid decline at 48 h may implicate the status of AKI.…”

Section: Discussionmentioning

confidence: 99%

Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway

Lin

et al. 2019

IJMS

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Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

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Expression of Kidney Injury Molecule-1 in Healthy and Diseased Feline Kidney Tissue

Cited by 26 publications

References 76 publications

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats

Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study

Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway

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