scholarly journals A new mouse model of hemorrhagic shock-induced acute kidney injury

2017 ◽  
Vol 312 (1) ◽  
pp. F134-F142 ◽  
Author(s):  
Lei Wang ◽  
Jiangping Song ◽  
Jacentha Buggs ◽  
Jin Wei ◽  
Shaohui Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Hemorrhagic Shock ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Sham Operation ◽  
Renal Pedicle ◽  
Acute Response ◽  
Radio Transmitters ◽  
Kidney Injury Molecule 1

Current animal models of hemorrhagic shock-induced acute kidney injury (HS-induced AKI) require extensive surgical procedures and constant monitoring of hemodynamic parameters. Application of these HS-induced AKI models in mice to produce consistent kidney injury is challenging. In the present study, we developed a simple and highly reproducible mouse model of HS-induced AKI by combining moderate bleeding and renal pedicle clamping, which was abbreviated as HS-AKI. HS was induced by retroorbital bleeding of 0.4 ml blood in C57BL/6 mice. Mice were left in HS stage for 30 min, followed by renal pedicle clamping for 18 min at 36.8–37.0°C. Mean arterial pressure (MAP) and heart rate were monitored with preimplanted radio transmitters throughout the experiment. The acute response in renal blood flow (RBF) triggered by HS was measured with transonic flow probe. Mice received sham operation; bleeding alone and renal pedicle clamping alone served as respective controls. MAP was reduced from 77 ± 4 to 35 ± 3 mmHg after bleeding. RBF was reduced by 65% in the HS period. Plasma creatinine and kidney injury molecule-1 levels were increased by more than 22-fold 24 h after reperfusion. GFR was declined by 78% of baseline 3 days after reperfusion. Histological examination revealed a moderate-to-severe acute tubular damage, mostly at the cortex-medulla junction area, followed by the medullar and cortex regions. HS alone did not induce significant kidney injury, but synergistically enhanced pedicle clamping-induced AKI. This is a well-controlled, simple, and reliable mouse model of HS-AKI.

Protection of resveratrol on acute kidney injury in septic rats

2016 ◽  
Vol 36 (10) ◽  
pp. 1015-1022 ◽  
Author(s):  
Y Gan ◽  
S Tao ◽  
D Cao ◽  
H Xie ◽  
Q Zeng
Keyword(s):  
Acute Kidney Injury ◽  
Survival Rate ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Sham Operation ◽  
Serum Cystatin C ◽  
Injury Index ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1

Aim: The aim of the study is to investigate protective effect of resveratrol (Res) on acute kidney injury (AKI) in sepsis. Methods: Rats in sham group received sham operation; in sham + Res received sham operation and Res (3 mg/kg); in cecal ligation and puncture (CLP) established as sepsis; in CLP + Res (3 mg/kg) with sepsis and Res (3 mg/kg); and in CLP + Res (10 mg/kg) with sepsis and Res (10 mg/kg). Survival rate, serum indexes, inflammatory factors, NF-κB-P65, and SIRT1 were detected. Lipopolysaccharide (LPS) mesangial cell was with Res and SIRT1 silencing. Results: (1) Res intervention improved survival rate of CLP rat. (2) Compared to sham, serum creatinine, blood urine nitrogen, serum cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, tumor necrosis factor-α, interleukin-1β, IL-6, and renal injury index increased in CLP group, while decreased in CLP + Res (3 mg/kg) and CLP + Res (10 mg/kg), significantly, as dose-dependent ( p < 0.05). (3) With Res, NF-κB-P65 and de-acetylated SIRT1 decreased, while SIRT1 and de-acetylated Nuclear factor kB-p65 9 NF-κB-P65) increased, significantly ( p < 0.05). (4) SIRT1 and de-acetylated NF-κB-P65 decreased in LPS cells, while SIRT1 increased after Res intervention, significantly ( p < 0.05). After silencing SIRT1, de-acetylated NF-κB-P65 increased, significantly ( p < 0.05). Conclusions: Res increases the survival rate of septic rats by inhibiting inflammatory factors to ease AKI and promotes NF-κB-P65 de-acetylation by upregulating SIRT1.

Cilastatin Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury in Mice

2021 ◽  
pp. ASN.2020030263
Author(s):  
Katsuyuki Matsushita ◽  
Kiyoshi Mori ◽  
Turgay Saritas ◽  
Mahaba Eiwaz ◽  
Yoshio Funahashi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Proximal Tubule ◽  
Critical Role ◽  
Kidney Injury ◽  
Pharmacologic Therapy ◽  
Proximal Tubule Cells ◽  
Gfr Decline ◽  
Kidney Injury Molecule 1 ◽  
Specific Deletion

Background Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of acute kidney injury (AKI) and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate chronic kidney disease (CKD). Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. Methods To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14-32 weeks old) with proximal tubule-specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. Results Inducible proximal tubule-specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved glomerular filtration rate (GFR), reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. Conclusions We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy.

scholarly journals NMR-based urine metabolic profiling and immunohistochemistry analysis of nephron changes in a mouse model of hypoxia-induced acute kidney injury

2018 ◽  
Vol 315 (4) ◽  
pp. F1159-F1173 ◽  
Author(s):  
Tafadzwa Chihanga ◽  
Hannah N. Ruby ◽  
Qing Ma ◽  
Sabina Bashir ◽  
Prasad Devarajan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Metabolic Profiling ◽  
Structural Changes ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Resonance Spectroscopy ◽  
Urine Metabolites ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1

Acute kidney injury can be caused by multiple factors, including sepsis, respiratory failure, heart failure, trauma, or nephrotoxic medications, among others. Here, a mouse model was used to investigate potential urinary metabolic biomarkers of hypoxia-induced AKI. Urine metabolic profiles of 48 Swiss Webster mice were assessed using nuclear magnetic resonance spectroscopy (NMR) for 7 days following 72 h exposure to a hypoxic 6.5% oxygen environment. Histological analyses indicated a lack of gross nephron structural changes in the aftermath of hypoxia. Immunohistochemical (IHC) analyses, however, indicated elevated expression of protein injury biomarkers in distal and proximal tubules but not glomeruli. Kidney injury molecule-1 levels peaked in distal tubules at 72 h and were still increasing in proximal tubules at 7 days posthypoxia, whereas cystatin C levels were elevated at 24 h but decreased thereafter, and were elevated and still increasing in proximal tubules at 7 days posthypoxia. Neutrophil gelatinase-associated lipocalin levels were modestly elevated from 24 h to 7 days posthypoxia. NMR-based metabolic profiling revealed that urine metabolites involved in energy metabolism and associated biosynthetic pathways were initially decreased at 24 h posthypoxia, consistent with metabolic suppression as a mechanism for cell survival, but were significantly elevated at 48 and 72 h posthypoxia, indicating a burst in organism metabolism associated with reactivation of cellular energetics during recovery after cessation of hypoxia and return to a normoxic environment. The IHC results indicated that kidney injury persists long after plasma and urine biomarkers of hypoxia return to normal values.

scholarly journals A zebrafish model of infection-associated acute kidney injury

2018 ◽  
Vol 315 (2) ◽  
pp. F291-F299 ◽  
Author(s):  
Xiaoyan Wen ◽  
Liyan Cui ◽  
Seth Morrisroe ◽  
Donald Maberry ◽  
David Emlet ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Unmet Need ◽  
Kidney Injury ◽  
Edwardsiella Tarda ◽  
Adult Zebrafish ◽  
Zebrafish Model ◽  
Pericardial Edema ◽  
Kidney Injury Molecule 1 ◽  
Dose Dependent

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

scholarly journals Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates

2015 ◽  
Vol 78 (4) ◽  
pp. 430-435 ◽  
Author(s):  
Vesna D. Stojanović ◽  
Nenad A. Barišić ◽  
Nada M. Vučković ◽  
Aleksandra D. Doronjski ◽  
Amira E. Peco Antić
Keyword(s):  
Acute Kidney Injury ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Kidney Injury ◽  
Rapid Test ◽  
Extremely Low Birth Weight ◽  
Kidney Injury Molecule 1

A case of immersion‐induced acute kidney injury: did momentary hypoxia affect tubular damage?

2018 ◽  
Vol 48 (11) ◽  
pp. 1410-1411
Author(s):  
Kyung Min Kim ◽  
Soon Kil Kwon ◽  
Hye‐Young Kim ◽  
Sun Moon Kim ◽  
Do Hee Kim ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Tubular Damage

scholarly journals Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury

2020 ◽  
Vol 92 (7) ◽  
pp. 63-69
Author(s):  
I. G. Rekhtina ◽  
E. V. Kazarina ◽  
E. S. Stolyarevich ◽  
A. M. Kovrigina ◽  
V. N. Dvirnyk ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Prognostic Value ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Response To Therapy ◽  
Tubular Damage ◽  
Renal Response ◽  
Cast Nephropathy ◽  
Myeloma Cast Nephropathy ◽  
E Cadherin

Aim.Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy. Materials and methods.Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission. Results.Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN. Conclusion.If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.

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