Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury

Acute kidney injury (AKI) due to ischemia is an important contributor to the progression of chronic kidney disease (CKD). Key mediators of cellular adaptation to hypoxia are oxygen-sensitive hypoxia-inducible factors (HIF), which are regulated by prolyl-4-hydroxylase domain (PHD)-containing dioxygenases. While activation of HIF protects from ischemic cell death, HIF has been shown to promote fibrosis in experimental models of CKD. The impact of HIF activation on AKI-induced fibrosis has not been defined. Here, we investigated the role of pharmacologic HIF activation in AKI-associated fibrosis and inflammation. We found that pharmacologic inhibition of HIF prolyl hydroxylation before AKI ameliorated fibrosis and prevented anemia, while inhibition of HIF prolyl hydroxylation in the early recovery phase of AKI did not affect short- or long-term clinical outcome. Therefore, preischemic targeting of the PHD/HIF pathway represents an effective therapeutic strategy for the prevention of CKD resulting from AKI, and it warrants further investigation in clinical trials.

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Research Progress on Regulatory T Cells in Acute Kidney Injury

Journal of Immunology Research ◽

10.1155/2015/174164 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Yamei Wang ◽

Yuhong Tao

Keyword(s):

Acute Kidney Injury ◽

T Cells ◽

Regulatory T Cells ◽

Therapeutic Potential ◽

Kidney Injury ◽

Recovery Phase ◽

Experimental Models ◽

Acute Injury ◽

Research Progress ◽

Protective Function

Immune inflammation is crucial in mediating acute kidney injury (AKI). Immune cells of both the innate and adaptive immune systems substantially contribute to overall renal damage in AKI. Regulatory T cells (Tregs) are key regulator of immunological function and have been demonstrated to ameliorate injury in several murine experimental models of renal inflammation. Recent studies have illuminated the renal-protective function of Tregs in AKI. Tregs appear to exert beneficial effects in both the acute injury phase and the recovery phase of AKI. Additionally, Tregs-based immunotherapy may represent a promising approach to ameliorate AKI and promote recovery from AKI. This review will highlight the recent insights into the role of Tregs and their therapeutic potential in AKI.

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Delayed recovery of renal regional blood flow in diabetic mice subjected to acute ischemic kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00215.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. F1512-F1517 ◽

Cited By ~ 34

Author(s):

Haikun Shi ◽

Daniel Patschan ◽

Tracy Epstein ◽

Michael S. Goligorsky ◽

Joseph Winaver

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Renal Function ◽

Renal Cortex ◽

Kidney Injury ◽

Recovery Phase ◽

Renal Ischemia ◽

Diabetic Mice ◽

Early Recovery ◽

Doppler Flowmetry

Ischemic acute kidney injury in experimental diabetes mellitus (DM) is associated with a more severe deterioration in renal function than shown in nondiabetic animals. We evaluated whether the early recovery phase from acute kidney injury is associated with a more prolonged and sustained decrease in renal perfusion in diabetic mice, which could contribute to the impaired recovery of renal function. Perfusion to the renal cortex and medulla was evaluated by laser-Doppler flowmetry in 10- to 12-wk-old anesthetized mice with type 2 DM ( db/db), heterozygous mice ( db/m), and nondiabetic (control) mice (C57BL/6J). After baseline measurements were obtained, the right renal artery was clampedfor 20 min followed by reperfusion for 60 min. The data demonstrated that, in all three groups studied, the reperfusion phase was characterized by a significant increase in the medullary-to-cortical blood flow ratio. Moreover, during recovery from ischemia, there was a marked prolongation in the time (in min) required to reach peak reperfusion in the cortex ( db/db: 20.7 ± 4.0, db/m: 12.92 ± 1.9, C57BL/6J: 9.3 ± 1.3) and the medulla ( db/db: 20.8 ± 3.2, db/m: 12.88 ± 1.89, C57BL/6J: 11.2 ± 1.2). Additionally, the slope of the recovery phase was lower in db/ db mice (cortex: 61.9 ± 23.1%/min, medulla: 16.3 ± 3.6%/min) than in C57BL/6J mice (cortex: 202.2 ± 41.6%/min, medulla: 42.1 ± 7.2%/min). Our findings indicate that renal ischemia is associated with a redistribution of blood flow from cortex to medulla, not related to DM. Furthermore, renal ischemia in db/db mice results in a marked impairment in reperfusion of the renal cortex and medulla during the early postischemic period.

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Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezab044 ◽

2021 ◽

Author(s):

Andrew M Vekstein ◽

Babtunde A Yerokun ◽

Oliver K Jawitz ◽

Julie W Doberne ◽

Jatin Anand ◽

...

Keyword(s):

Acute Kidney Injury ◽

Circulatory Arrest ◽

Aortic Surgery ◽

Multivariable Analysis ◽

Kidney Injury ◽

Deep Hypothermia ◽

Moderate Hypothermia ◽

Bladder Temperature ◽

Increased Risk ◽

The Impact

Abstract OBJECTIVES The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS A total of 85% (n = 645) of patients underwent deep hypothermia (14.1–20.0°C), 11% (n = 83) low-moderate hypothermia (20.1–24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1–28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1–34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P > 0.05). CONCLUSIONS In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

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Indications for Dialysis in Acute Kidney Injury

10.2310/nephro.12038 ◽

2020 ◽

Author(s):

Ankit Patel ◽

Kenneth B Christopher

Keyword(s):

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

High Efficiency ◽

Kidney Injury ◽

Intermittent Hemodialysis ◽

Continuous Venovenous Hemofiltration ◽

Continuous Venovenous Hemodialysis ◽

Low Efficiency ◽

The Impact

Renal replacement therapy (RRT) can be used to support patient’s kidney function in cases of acute kidney injury (AKI). However, timing, modality, and dosing of RRT continue to remain in question. Recent studies have begun to provide data to help guide clinicians on when to initiate RRT, what form of RRT to use ranging from continuous venovenous hemofiltration (VVH) to intermittent hemodialysis, and the impact of high versus low-intensity dosing. Additionally, the risks associated with temporary vascular access with regard to thrombosis and infection, the impact of high efficiency and flux versus low efficiency and flux membranes, and options for anticoagulation in RRT for AKI are also discussed. This review contains 75 references. Key words: acute kidney injury, chronic kidney disease, continuous venovenous hemofiltration, continuous venovenous hemodialysis, renal replacement therapy, venovenous hemofiltration,

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Acute Kidney Injury and Acute Liver Failure in Leptospira Infection and Weil’s Syndrome

Journal of Renal and Hepatic Disorders ◽

10.15586/jrenhep.2020.75 ◽

2020 ◽

Vol 4 (2) ◽

pp. 21-28

Author(s):

Jonathan S Chávez-Iñiguez ◽

Jose Said Cabrera-Aguilar ◽

Guillermo Garcia-Garcia ◽

Juan Armendáriz-Borunda

Keyword(s):

Acute Kidney Injury ◽

Clinical Presentation ◽

Clinical Signs ◽

Kidney Injury ◽

Organ Damage ◽

Multiple Organ ◽

Serological Tests ◽

Microbiological Criteria ◽

Sanitary Conditions ◽

The Impact

Leptospirosis is considered a zoonosis acquired predominantly from contaminated surfaces and water, more commonly in emerging countries with limited sanitary conditions. Leptospira in the host unleashes an immune response that explains the symptoms and clinical signs; once it reaches the kidney and liver tissue, it can manifest with alterations that lead to acute and chronic diseases in both organs. Weil’s syndrome is the best known clinical manifestation with jaundice and acute kidney injury that could lead to multiple organ failure and death. For its diagnosis, there are simplified scores such as the SPiRO score, the microbiological criteria by microscopy or serological tests; the treatment focuses on antibiotics and, if necessary, provides organic support until the infection is curtailed. The purpose of this review was to address the impact of Lep-tospira infection on the kidney and liver, the mechanisms of organ damage, the clinical presentation, and diagnosis and management of this disease.

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Hydroxyethyl Starch 130/0.42 Effect’s on Renal Function in Patients After Cardiac Surgery: A Retrospective Cohort Analysis

10.21203/rs.3.rs-100124/v1 ◽

2020 ◽

Author(s):

Benedict Morath ◽

Andreas Meid ◽

Johannes Rickmann ◽

Jasmin Soethoff ◽

Markus Verch ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Cardiac Surgery ◽

Kidney Function ◽

Hydroxyethyl Starch ◽

Retrospective Cohort ◽

Cohort Analysis ◽

Kidney Injury ◽

Retrospective Cohort Analysis ◽

The Impact

Abstract Background: Fluid management is an everyday challenge in intensive care units worldwide. Data from recent trials suggest that the use of hydroxyethyl starch leads to a higher rate of acute kidney injury and mortality in septic patients. Evidence on the safety of hydroxyethyl starch used in postoperative cardiac surgery patients is lacking Methods: The aim was to determine the impact of postoperatively administered hydroxyethylstarch 130/0.42 on renal function and 90-day mortality compared to with or without balanced crystalloids in patients after elective cardiac surgery. A retrospective cohort analysis was performed including 2245 patients undergoing elective coronary artery bypass grafting or, aortic valve replacement, or a combination of both between 2015 - 2019. Acute kidney injury was defined according to the ‘kidney disease improving global outcomes’ criteria. Multivariate logistic regression yielded adjusted associations of postoperative hydroxyethyl starch administration with acute kidney injury during hospital stay and 90-day mortality. Linear mixed-effects models predicted trajectories of estimated glomerular filtration rates over the postoperative period to explore the impact of dosage and timing of hydroxyethyl starch administration.Results: A total of 1009 patients (45.0 %) suffered from acute kidney injury. Significantly less acute kidney injury of any stage occurred in patients receiving hydroxyethyl starch compared to patients receiving only crystalloids for fluid resuscitation (43.7 % vs. 51.2 % p=0.008). In multivariate analysis, the administration of hydroxyethyl starch showed a protective effect (OR 0.89 95% confidence interval (CI) (0.82-0.96)) which was less prominent in patients receiving only crystalloids (OR 0.98, 95% CI (0.95-1.00)). No association between hydroxyethyl starch and 90-day mortality (OR 1.05 95% CI (0.88-1.25)) was detected. Renal function trajectories were dose-dependent and biphasic and hydroxyethyl starch could even slow down the late postoperative decline of kidney function.Conclusion: This study showed no association between hydroxyethyl starch and the postoperative occurrence of acute kidney injury and may add evidence to the discussion about the use of hydroxyethyl starch in cardiac surgery patients. In addition, hydroxyethyl starch administered early after surgery in adequate low doses might even prevent the decline of the kidney function after cardiac surgery.

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The Impact of Post-contrast Acute Kidney Injury on In-hospital Mortality After Endovascular Thrombectomy in Patients With Acute Ischemic Stroke

Frontiers in Neurology ◽

10.3389/fneur.2021.665614 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mona Laible ◽

Ekkehart Jenetzky ◽

Markus Alfred Möhlenbruch ◽

Martin Bendszus ◽

Peter Arthur Ringleb ◽

...

Keyword(s):

Acute Kidney Injury ◽

Ischemic Stroke ◽

Hospital Mortality ◽

Acute Ischemic Stroke ◽

Kidney Injury ◽

Stroke Severity ◽

Post Contrast ◽

Endovascular Thrombectomy ◽

Symptomatic Intracerebral Hemorrhage ◽

The Impact

Background and Purpose: Clinical outcome and mortality after endovascular thrombectomy (EVT) in patients with ischemic stroke are commonly assessed after 3 months. In patients with acute kidney injury (AKI), unfavorable results for 3-month mortality have been reported. However, data on the in-hospital mortality after EVT in this population are sparse. In the present study, we assessed whether AKI impacts in-hospital and 3-month mortality in patients undergoing EVT.Materials and Methods: From a prospectively recruiting database, consecutive acute ischemic stroke patients receiving EVT between 2010 and 2018 due to acute large vessel occlusion were included. Post-contrast AKI (PC-AKI) was defined as an increase of baseline creatinine of ≥0.5 mg/dL or >25% within 48 h after the first measurement at admission. Adjusting for potential confounders, associations between PC-AKI and mortality after stroke were tested in univariate and multivariate logistic regression models.Results: One thousand one hundred sixty-nine patients were included; 166 of them (14.2%) died during the acute hospital stay. Criteria for PC-AKI were met by 29 patients (2.5%). Presence of PC-AKI was associated with a significantly higher risk of in-hospital mortality in multivariate analysis [odds ratio (OR) = 2.87, 95% confidence interval (CI) = 1.16–7.13, p = 0.023]. Furthermore, factors associated with in-hospital mortality encompassed higher age (OR = 1.03, 95% CI = 1.01–1.04, p = 0.002), stroke severity (OR = 1.05, 95% CI = 1.03–1.08, p < 0.001), symptomatic intracerebral hemorrhage (OR = 3.20, 95% CI = 1.69–6.04, p < 0.001), posterior circulation stroke (OR = 2.85, 95% CI = 1.72–4.71, p < 0.001), and failed recanalization (OR = 2.00, 95% CI = 1.35–3.00, p = 0.001).Conclusion: PC-AKI is rare after EVT but represents an important risk factor for in-hospital mortality and for mortality within 3 months after hospital discharge. Preventing PC-AKI after EVT may represent an important and potentially lifesaving effort in future daily clinical practice.

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