scholarly journals A new model of an arteriovenous fistula in chronic kidney disease in the mouse: beneficial effects of upregulated heme oxygenase-1

2016 ◽  
Vol 310 (6) ◽  
pp. F466-F476 ◽  
Author(s):  
Lu Kang ◽  
Joseph P. Grande ◽  
Matthew L. Hillestad ◽  
Anthony J. Croatt ◽  
Michael A. Barry ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Blood Flow ◽  
Kidney Disease ◽  
Arteriovenous Fistula ◽  
Heme Oxygenase ◽  
Viral Gene ◽  
Heme Oxygenase 1 ◽  
Beneficial Effects ◽  
Viral Gene Delivery ◽  
Venous Wall

The arteriovenous fistula (AVF) is the preferred hemodialysis vascular access, but it is complicated by high failure rates and attendant morbidity. This study provides the first description of a murine AVF model that recapitulates two salient features of hemodialysis AVFs, namely, anastomosis of end-vein to side-artery to create the AVF and the presence of chronic kidney disease (CKD). CKD reduced AVF blood flow, observed as early as 3 days after AVF creation, and increased neointimal hyperplasia, venous wall thickness, thrombus formation, and vasculopathic gene expression in the AVF. These adverse effects of CKD could not be ascribed to preexisting alterations in blood pressure or vascular reactivity in this CKD model. In addition to vasculopathic genes, CKD induced potentially vasoprotective genes in the AVF such as heme oxygenase-1 (HO-1) and HO-2. To determine whether prior HO-1 upregulation may protect in this model, we upregulated HO-1 by adeno-associated viral gene delivery, achieving marked venous induction of the HO-1 protein and HO activity. Such HO-1 upregulation improved AVF blood flow and decreased venous wall thickness in the AVF. Finally, we demonstrate that the administration of carbon monoxide, a product of HO, acutely increased AVF blood flow. This study thus demonstrates: 1) the feasibility of a clinically relevant murine AVF model created in the presence of CKD and involving an end-vein to side-artery anastomosis; 2) the exacerbatory effect of CKD on clinically relevant features of this model; and 3) the beneficial effects in this model conferred by HO-1 upregulation by adeno-associated viral gene delivery.

scholarly journals Renal protection in chronic kidney disease: hypoxia-inducible factor activation vs. angiotensin II blockade

2010 ◽  
Vol 299 (6) ◽  
pp. F1365-F1373 ◽  
Author(s):  
Aihua Deng ◽  
Mary Ann K. Arndt ◽  
Joseph Satriano ◽  
Prabhleen Singh ◽  
Timo Rieg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Real Time ◽  
Heme Oxygenase ◽  
Real Time Pcr ◽  
Hypoxia Inducible Factor ◽  
Heme Oxygenase 1 ◽  
Ang Ii

The 5/6thnephrectomy or ablation/infarction (A/I) preparation has been used as a classic model of chronic kidney disease (CKD). We observed increased kidney oxygen consumption (QO2) and altered renal hemodynamics in the A/I kidney that were normalized after combined angiotensin II (ANG II) blockade. Studies suggest hypoxia inducible factor as a protective influence in A/I. We induced hypoxia-inducible factor (HIF) and HIF target proteins by two different methods, cobalt chloride (CoCl2) and dimethyloxalyglycine (DMOG), for the first week after creation of A/I and compared the metabolic and renal hemodynamic outcomes to combined ANG II blockade. We also examined the HIF target proteins expressed by using Western blots and real-time PCR. Treatment with DMOG, CoCl2, and ANG II blockade normalized kidney oxygen consumption factored by Na reabsorption and increased both renal blood flow and glomerular filtration rate. At 1 wk, CoCl2and DMOG increased kidney expression of HIF by Western blot. In the untreated A/I kidney, VEGF, heme oxygenase-1, and GLUT1 were all modestly increased. Both ANG II blockade and CoCl2therapy increased VEGF and GLUT1 but the cobalt markedly so. ANG II blockade decreased heme oxygenase-1 expression while CoCl2increased it. By real-time PCR, erythropoietin and GLUT1 were only increased by CoCl2therapy. Cell proliferation was modestly increased by ANG II blockade but markedly after cobalt therapy. Metabolic and hemodynamic abnormalities were corrected equally by ANG II blockade and HIF therapies. However, the molecular patterns differed significantly between ANG II blockade and cobalt therapy. HIF induction may prove to be protective in this model of CKD.

The Impact of Multidisciplinary Collaborative Nursing Intervention on Arteriovenous Fistula in Patients Undergoing Hemodialysis

2021 ◽  
pp. 105477382110371
Author(s):  
Danfeng Zha ◽  
Xionghao Yang ◽  
Yan Yang ◽  
Haifen Zhang ◽  
Yan Jin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Blood Flow ◽  
Kidney Disease ◽  
Arteriovenous Fistula ◽  
Nursing Intervention ◽  
Vessel Diameter ◽  
Hemodialysis Patients ◽  
Control Group ◽  
The Impact ◽  
Intervention Procedure

This study was conducted to evaluate the effect of multidisciplinary collaborative nursing intervention on AVF in patients with chronic kidney disease (CKD) undergoing hemodialysis. Patients ( n = 84) with CKD who underwent the first autologous AVF were randomly divided into control group and multidisciplinary collaborative nursing intervention (MCNI) group and they received routine nursing procedure and multidisciplinary collaborative nursing intervention procedure, respectively. The natural blood flow and vessel diameter in MCNI group were higher than that in control group at the fourth week after surgery ( p < .05). The vessel diameter in MCNI group at 2 and 4 weeks after operation was significantly larger than that in control group ( p < .05).In conclusions, the implementation of multidisciplinary collaborative nursing intervention procedure can significantly promote the maturation of AVF, effectively increase the blood flow of AVF and promote the growth of vessel diameter.

scholarly journals Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight

2021 ◽  
Vol 22 (12) ◽  
pp. 6270
Author(s):  
Chia-Ter Chao ◽  
Shih-Hua Lin
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Uremic Toxins ◽  
Heme Oxygenase 1 ◽  
Signal Pathways ◽  
Uremic Toxin ◽  
Nuclear Factor ◽  
Cognitive Frailty ◽  
Renal Function Decline

The accumulation of uremic toxins (UTs) is a prototypical manifestation of uremic milieu that follows renal function decline (chronic kidney disease, CKD). Frailty as a potential outcome-relevant indicator is also prevalent in CKD. The intertwined relationship between uremic toxins, including small/large solutes (phosphate, asymmetric dimethylarginine) and protein-bound ones like indoxyl sulfate (IS) and p-cresyl sulfate (pCS), and frailty pathogenesis has been documented recently. Uremic toxins were shown in vitro and in vivo to induce noxious effects on many organ systems and likely influenced frailty development through their effects on multiple preceding events and companions of frailty, such as sarcopenia/muscle wasting, cognitive impairment/cognitive frailty, osteoporosis/osteodystrophy, vascular calcification, and cardiopulmonary deconditioning. These organ-specific effects may be mediated through different molecular mechanisms or signal pathways such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), mitogen-activated protein kinase (MAPK) signaling, aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Runt-related transcription factor 2 (RUNX2), bone morphogenic protein 2 (BMP2), osterix, Notch signaling, autophagy effectors, microRNAs, and reactive oxygen species induction. Anecdotal clinical studies also suggest that frailty may further accelerate renal function decline, thereby augmenting the accumulation of UTs in affected individuals. Judging from these threads of evidence, management strategies aiming for uremic toxin reduction may be a promising approach for frailty amelioration in patients with CKD. Uremic toxin lowering strategies may bear the potential of improving patients’ outcomes and restoring their quality of life, through frailty attenuation. Pathogenic molecule-targeted therapeutics potentially disconnect the association between uremic toxins and frailty, additionally serving as an outcome-modifying approach in the future.

Beneficial effects of water-based exercise in patients with chronic kidney disease

2003 ◽  
Vol 26 (2) ◽  
pp. 153-156 ◽  
Author(s):  
??lle Pechter ◽  
Mai Ots ◽  
Siiri Mesikepp ◽  
Kersti Zilmer ◽  
Tiiu Kullissaar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Beneficial Effects ◽  
Water Based

Products of heme oxygenase and their potential therapeutic applications

2006 ◽  
Vol 290 (3) ◽  
pp. F563-F571 ◽  
Author(s):  
Kristin A. Kirkby ◽  
Christopher A. Adin
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Inexpensive Method ◽  
Waste Products ◽  
Biliverdin Reductase ◽  
Therapeutic Applications ◽  
Beneficial Effects ◽  
Tissue Protection ◽  
Organ Systems ◽  
Dose Dependent

Heme oxygenase 1 (HO-1) is induced in response to cellular stress and is responsible for converting the prooxidant heme molecule into equimolar quantities of biliverdin (BV), carbon monoxide (CO), and iron. BV is then converted to bilirubin (BR) by the enzyme biliverdin reductase. Experimental evidence suggests that induction of the HO system is an important endogenous mechanism for cytoprotection and that the downstream products of heme degradation, CO, BR, and BV, may mediate these powerful beneficial effects. These molecules, which were once considered to be toxic metabolic waste products, have recently been shown to have dose-dependent vasodilatory, antioxidant, and anti-inflammatory properties that are particularly desirable for tissue protection during organ transplantation. In fact, recent work has demonstrated that administration of exogenous CO, BR, or BV may offer a simple, inexpensive method to substitute for the cytoprotective effects of HO-1 in a variety of clinically applicable models. This review will attempt to summarize the relevant biochemical and cytoprotective properties of CO, BR, and BV, and will discuss emerging studies involving the therapeutic applications of these molecules in the kidney and other organ systems.

scholarly journals Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Heme Oxygenase 1 ◽  
Wide Range ◽  
Significant Burden ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Effect

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

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