scholarly journals MMP-9 gene deletion mitigates microvascular loss in a model of ischemic acute kidney injury

2011 ◽  
Vol 301 (1) ◽  
pp. F101-F109 ◽  
Author(s):  
So-Young Lee ◽  
Markus Hörbelt ◽  
Henry E. Mang ◽  
Nicole L. Knipe ◽  
Robert L. Bacallao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Gene Deletion ◽  
Kidney Injury ◽  
Ischemic Injury ◽  
Microvascular Density ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Bilateral Renal Artery ◽  
Endothelial Growth Factor ◽  
Microvascular Rarefaction

Microvascular rarefaction following an episode of acute kidney injury (AKI) is associated with renal hypoxia and progression toward chronic kidney disease. The mechanisms contributing to microvascular rarefaction are not well-understood, although disruption in local angioregulatory substances is thought to contribute. Matrix metalloproteinase (MMP)-9 is an endopeptidase important in modifying the extracellular matrix (ECM) and remodeling the vasculature. We examined the role of MMP-9 gene deletion on microvascular rarefaction in a rodent model of ischemic AKI. MMP-9-null mice and background control (FVB/NJ) mice were subjected to bilateral renal artery clamping for 20 min followed by reperfusion for 14, 28, or 56 days. Serum creatinine level in MMP-9-null mice 24 h after injury [1.4 (SD 0.8) mg/dl] was not significantly different from FVB/NJ mice [1.5 (SD 0.6) mg/dl]. Four weeks after ischemic injury, FVB/NJ mice demonstrated a 30–40% loss of microvascular density compared with sham-operated (SO) mice. In contrast, microvascular density was not significantly different in the MMP-9-null mice at this time following injury compared with SO mice. FVB/NJ mice had a 50% decrease in tissue vascular endothelial growth factor (VEGF) 2 wk after ischemic insult compared with SO mice. A significant difference in VEGF was not observed in MMP-9-null mice compared with SO mice. There was no significant difference in the liberation of angioinhibitory fragments from the ECM between MMP-9-null mice and FVB/NJ mice following ischemic injury. In conclusion, MMP-9 deletion stabilizes microvascular density following ischemic AKI in part by preserving tissue VEGF levels.

Acute and chronic microvascular alterations in a mouse model of ischemic acute kidney injury

2007 ◽  
Vol 293 (3) ◽  
pp. F688-F695 ◽  
Author(s):  
Markus Hörbelt ◽  
So-Young Lee ◽  
Henry E. Mang ◽  
Nicole L. Knipe ◽  
Yoshikazu Sado ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Endothelial Cells ◽  
Mouse Model ◽  
Kidney Injury ◽  
Ischemic Injury ◽  
Microvascular Density ◽  
Microvascular Permeability ◽  
Microvascular Endothelial Cells ◽  
Ischemic Acute Kidney Injury ◽  
Microvascular Endothelial

Functional and structural abnormalities in the renal microvasculature are important processes contributing to the pathophysiology of ischemic acute kidney injury (AKI). In this study, we examine the contribution of endothelial cell loss via apoptosis on microvascular permeability and rarefaction in a mouse model of ischemic AKI. Three-dimensional reconstructions of microvascular networks obtained 24 h following acute ischemic injury demonstrate an intact endothelial monolayer in areas of increased microvascular permeability. A 45% decrease in microvascular density was observed 4 wk after acute ischemic injury. Examination of microvascular endothelial cells following acute ischemic injury did not reveal evidence of positive terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining at 1, 2, 8, and 16 days following ischemia; however, activation of caspase-3 was evident in endothelial cells following acute ischemic injury. Examination of angiopoietin (Ang) protein expression in the kidney 24 h after ischemic injury revealed an eightfold increase in Ang-1 but no significant change in Ang-2. No significant difference in the expression of vascular endothelial growth factor or Ang-2 was observed 4 wk after ischemic injury, although an almost twofold elevation in Ang-1 was observed. An increase in angiostatic breakdown products of collagen IV was observed at both 24 h and 4 wk after ischemic injury. Taken together, these findings indicate that the loss of endothelial cells following ischemic injury is not a major contributor to altered microvascular permeability, although renal microvascular endothelial cells are vulnerable to the initiation of apoptotic mechanisms following ischemic injury that can ultimately impact microvascular density.

scholarly journals P7: ACUTE KIDNEY INJURY AFTER ELECTIVE COLORECTAL SURGERY: RESULTS OF A NATIONAL CLOSED-LOOP AUDIT

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
Keyword(s):  
Acute Kidney Injury ◽  
Quality Improvement ◽  
Colorectal Surgery ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Kidney Injury ◽  
Elective Colorectal Surgery ◽  
National Quality ◽  
Significant Difference ◽  
The Uk

Abstract Introduction The aim of this study was to re-audit the rates of acute kidney injury (AKI) after elective colorectal surgery, following local presentations of results. Method Outcomes After Kidney injury in Surgery (OAKS) and Ileus Management International (IMAGINE), were prospective multicentre audits on consecutive elective colorectal resections, in the UK and Ireland. These were performed over 3-month periods in 2015 and 2018 respectively. During the interim period, results were presented at participating centres to stimulate local quality improvement initiatives. Risk-adjusted 7-day postoperative AKI rates were calculated through multilevel logistic regression based on the OAKS prognostic score. Result Of the 4,917 patients included, 3,133 (63.7%) originated from OAKS and 1,784 (36.3%) from IMAGINE. On univariate analysis, there was no significant difference (p=0.737) in the 7-day AKI rate between OAKS (n=346, 11.8%) and IMAGINE (n=205, 11.5%). However, the risk-adjusted AKI rate in IMAGINE was significantly lower compared to OAKS (-1.8%, 95% CI: -2.3% to -1.3%, p<0.001). Of 47 centres (40.1%) with a recorded local presentation, there was no significant difference in the subsequent AKI rate in IMAGINE (-0.7%, -2.0% to 0.6%, p=0.278). Conclusion Rates of AKI after elective colorectal surgery significantly reduced on re-audit. However, this may be related to increased awareness from participation or national quality improvement initiatives, rather than local presentation of results. Abbrev. AKI - Acute Kidney Injury, OAKS - Outcomes After Kidney injury in Surgery, IMAGINE - Ileus Management International Take-home message Risk-adjusted AKI rates significantly reduced on re-audit, however, this was most likely due to factors separate from the local presentation of initial results.

scholarly journals Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1099
Author(s):  
Pedro Pinto-Bravo ◽  
Maria Rosa Rebordão ◽  
Ana Amaral ◽  
Carina Fernandes ◽  
António Galvão ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Microvascular Density ◽  
Angiogenic Factors ◽  
Protein Abundance ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Vascular Area ◽  
Endothelial Growth Factor

The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (FGF1, FGF2, VEGF) and their receptors—FGFR1, FGFR2, KDR, respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares’ oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest number of vascular structures in the follicular phase. Transcripts (qPCR) and relative protein abundance (Western blot) of angiogenic factors fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all oviduct portions throughout the estrous cycle. Upregulation of the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus and of FGF2 and KDR in the isthmus were noted. Furthermore, in the isthmus, the relative protein abundance of FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its three portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.

scholarly journals 113 Improving Intravenous Fluid Therapy to Reduce the Incidence of Acute Kidney Injury in Elderly Hip Fracture Patients

2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
C McCann ◽  
A Hall ◽  
J Min Leow ◽  
A Harris ◽  
N Hafiz ◽  
...  
Keyword(s):  
Emergency Department ◽  
Acute Kidney Injury ◽  
Hip Fracture ◽  
Length Of Stay ◽  
Kidney Injury ◽  
Ward Round ◽  
Fluid Administration ◽  
Ward Staff ◽  
Intravenous Fluid Therapy ◽  
Significant Difference

Abstract Background Acute kidney injury (AKI) in hip fracture patients is associated with morbidity, mortality, and increased length of stay. To avoid this our unit policy recommends maintenance crystalloid IV fluids of >62.5 mL/Hr for hip fracture patients. However, audits have shown that many patients still receive inadequate IV fluids. Methods Three prospective audits, each including 100 consecutive acute hip fracture patients aged >55, were completed with interventional measures employed between each cycle. Data collection points included details of IV fluid administration and pre/post-operative presence of AKI. Interventions between cycles included a revised checklist for admissions with a structured ward round tool for post-take ward round and various educational measures for Emergency Department, nursing and admitting team staff with dissemination of infographic posters, respectively. Results Cycle 1: 64/100 (64%) patients received adequate fluids. No significant difference in developing AKI post operatively was seen in patients given adequate fluids (2/64, 3.1%) compared to inadequate fluids (4/36, 11.1%; p = 0.107). More patients with pre-operative AKI demonstrated resolution of AKI with appropriate fluid prescription (5/6, 83.3%, vs 0/4, 0%, p < 0.05) Cycle 2: Fewer patients were prescribed adequate fluids (54/100, 54%). There was no significant difference in terms of developing AKI post operatively between patients with adequate fluids (4/54, 7.4%) or inadequate fluids (2/46, 4.3%; p = 0.52). Resolution of pre-operative AKI was similar in patients with adequate or inadequate fluid administration (4/6, 67% vs 2/2, 100%). Cycle 3: More patients received adequate fluids (79/100, 79%, p < 0.05). Patients prescribed adequate fluids were less likely to develop post-operative AKI than those receiving inadequate fluids (2/79, 2.5% vs 3/21, 14.3%; p < 0.05). Discussion This audit demonstrates the importance of administering appropriate IV fluid in hip fracture patients to avoid AKI. Improving coordination with Emergency Department and ward nursing/medical ward staff was a critical step in improving our unit’s adherence to policy.

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