scholarly journals Arterial hypertension and unusual ascending aortic dilatation in a neonate with acute kidney injury: mechanistic computer modelling

2018 ◽  
Author(s):  
Sanjay R Kharche
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Ascending Aorta ◽  
Small Vessel ◽  
Aortic Dilatation ◽  
Small Vessels ◽  
Left Ventricle Hypertrophy ◽  
Vessel Resistance ◽  
Underlying Mechanisms ◽  
Ventricle Hypertrophy

Background: Neonatal asphyxia caused acute kidney injury and severe hypertension in a newborn patient. An unusually dilatated ascending aorta developed within a few weeks. Dialysis and hypertensive treatment led to partial recovery of the aortic diameters. It was hypothesized that the aortic dilatation may be associated with cardiovascular changes induced by the acute kidney injury. Mathematical modelling was used to better understand the underlying mechanisms of hypertension and aortic dilatation.Methods: Patient observation included systolic blood pressure recording and echocardiographic exams. To explore underlying mechanisms of aortic dilatation and hypertension, a previous whole-body lumped parameter hemodynamics model was adapted to this study. Computer simulations were designed to permit dissection of individual mechanisms. The hypertension inducing effects of altering systemic vascular resistances, stiffnesses, and heart rate on blood flows and pressures were simulated.Results: In agreement with our clinical diagnosis, the mathematical model showed that an increase of systemic small vessel resistance is the prime cause of hypertension. Further, aortic stiffening may also cause hypertension, it was found to be secondary to the potency of systemic small vessel resistance. The cardiac output, as quantified using pressure-volume loop area, reduced significantly due to hypertension. Simultaneous left ventricle hypertrophy and small vessel blocking increased ascending aorta blood flow as well as pressure indicating an enlarged ascending aorta. In contrast, increased arterial stiffness appeared to lower the aortic blood flow and pressures.Conclusions and discussion: Systemic small vessel resistance is an important factor in arterial hypertension, and may also be a key clinical therapeutic target. Left ventricle hypertrophy may also be simultaneously ameliorated when treating systemic small vessels. Treatment of arterial stiffness appears to provide significant benefit but may be secondary to treatment of the systemic small vessels. The quantitative grading of pathophysiological mechanisms provided by the modelling may contribute to treatment recommendations. Further development and individualization of the model will augment its applicability in clinical practice.

scholarly journals P0475CRESCENTIC GLOMERULONEPHRITIS FOLLOWING HCV TREATMENT WITH DAAS, THE NON-CLASSIC TALE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mohamed Elrggal ◽  
Mariam Emam ◽  
Wesam Ismail
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Sustained Viral Response ◽  
Kidney Injury ◽  
Small Vessel ◽  
Small Vessel Vasculitis ◽  
Hcv Treatment ◽  
Drug Induced ◽  
First Case ◽  
Necrotizing Glomerulonephritis

Abstract Background and Aims Observational studies suggest that acute kidney injury may occur in up to 15% of patients treated with sofosbuvir based regimens. Histological findings show features of acute interstitial nephritis (AIN) or acute tubular necrosis (ATN). Here, we report the first case of small vessel vasculitis following sofosbuvir treatment. Method A 65-year-old female with controlled T2DM was recently diagnosed with HCV. She attained sustained viral response (SVR) after a three-month course of (sofosbuvir + daclatasvir + ribavirin). Kidney functions were normal pre and post treatment. Three months later, she presented with puffiness, bilateral lower extremities edema (no rash) and vomiting. Labs showed acute kidney injury (AKI), nephrotic proteinuria and haematuria (table 1). Immunological investigations (C3, C4, ANA, ANCA and anti-GBM), paraproteinemia workup and cryoglobulins were all negative. Renal US was also normal. Kidney biopsy revealed focal necrotizing glomerulonephritis with 70% crescents (figure 3,4). No chronic changes were detected in the glomeruli, interstitium or tubules. The patient received pulse methylprednisolone 0.5 gm for 3 days followed by oral prednisolone 60 mg/day. Oral cyclophosphamide was initiated at 150 mg after biopsy result was obtained. Our patient showed clinical and laboratory improvement (figure 1,2), however, she developed bone marrow suppression that required cessation of cyclophosphamide. Valsartan initiated to control proteinuria with slight increase in serum creatinine to 1.4 mg/dl. The patient is still under close follow up every two weeks, with a plan to introduce rituximab if serum creatinine continued to increase. Results AKI following HCV treatment with DAA has been reported. Explanation includes AIN, ATN and cryoglobulinemic vasculitis (CV). AIN and ATN usually occur during the treatment course, which is not the case in our patient as she developed AKI three months following the end of the treatment, and the biopsy did not show signs of either ATN or AIN. New onset CV has been reported previously in 3 case reports following SVR after DAA treatment. Previous reports explained that HCV can induce B-cell clonal proliferation that may persist independent of viral eradication and produce IgM kappa which will result in cryoglobulinemic GN, again this is not true in our case. Our patient did not have a rash, her serum cryoglobulin was negative and complement levels (C3 and C4) were normal and biopsy did not show evidence of CV. As far as we know, this is the first case with suspected sofosbuvir associated small vessel vasculitis to be reported. Despite the patient had a negative serum ANCA levels, we suspect that this is a case of drug induced vasculitis. Drug induced vasculitis has been reported with hydralazine, propylthiouracil and cocaine, none of these drugs were used in our case. Also, there is no reported case of vasculitis associated with ribavirin or daclatasvir. Thus, we suspect Sofosbuvir is the cause of drug induced vasculitis in this patient. Conclusion Crescentic GN following HCV treatment using DAA is a serious complication that should be promptly diagnosed and managed. Physicians treating HCV infected patients should be aware of this possible complication and monitor for kidney function even after achieving SVR.

Acute kidney injury after composite valve-graft replacement for ascending aorta aneurysms

2012 ◽  
Vol 28 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Giovanni Mariscalco ◽  
Francesco Nicolini ◽  
Antonio Scannapieco ◽  
Riccardo Gherli ◽  
Filiberto Serraino ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Ascending Aorta ◽  
Graft Replacement

scholarly journals Role of Intracellular Ca2+and Na+/Ca2+Exchanger in the Pathogenesis of Contrast-Induced Acute Kidney Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Dingping Yang ◽  
Dingwei Yang
Keyword(s):  
Acute Kidney Injury ◽  
Cell Injury ◽  
Kidney Injury ◽  
Renal Tubular Cell ◽  
Voltage Dependent ◽  
Key Factor ◽  
Intracellular Ca ◽  
Underlying Mechanisms ◽  
Renal Tubular

The precise mechanisms underlying contrast-induced acute kidney injury (CI-AKI) are not well understood. Intracellular Ca2+overload is considered to be a key factor in CI-AKI. Voltage-dependent Ca2+channel (VDC) and Na+/Ca2+exchanger (NCX) system are the main pathways of intracellular Ca2+overload in pathological conditions. Here, we review the potential underlying mechanisms involved in CI-AKI and discuss the role of NCX-mediated intracellular Ca2+overload in the contrast media-induced renal tubular cell injury and renal hemodynamic disorder.

scholarly journals Tofacitinib Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Blocking the JAK-STAT1/STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yang Yun ◽  
Jingyu Chen ◽  
Xuejiao Wang ◽  
Yingzhuo Li ◽  
Zhifan Hu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Inhibitory Effect ◽  
Janus Kinase ◽  
Protective Effects ◽  
Lps Challenge ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Septic Acute Kidney Injury ◽  
Underlying Mechanisms

Septic acute kidney injury (AKI) is the most common AKI syndrome in the intensive care unit (ICU), and it accounts for approximately half of AKI cases. Tofacitinib (TOFA) is a pan-Janus kinase (JAK) inhibitor that exhibits potent anti-inflammatory activity in rheumatoid arthritis. However, no study has examined the functional role of TOFA in septic AKI. In the present study, we investigated the protective effects of TOFA on septic AKI and the underlying mechanisms. A lipopolysaccharide- (LPS-) induced AKI model was established in C57BL/6 mice via an intraperitoneal injection of LPS (10 mg/kg). One hour after LPS challenge, the mice were orally administered TOFA (5, 10, or 15 mg/kg) every 6 h until sacrifice at 24 h. We found that TOFA significantly ameliorated LPS-induced renal histopathological changes and dysfunction. TOFA also suppressed the expression levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) and the parameters of oxidative stress (MDA, GSH, SOD, and CAT) in kidney tissues. These results may be associated with the inhibitory effect of TOFA on the JAK-STAT1/STAT3 pathway, which was significantly activated by LPS challenge. TOFA treatment also inhibited LPS-induced activation of the TLR4/NF-κB pathway. In conclusion, we revealed that TOFA had a protective effect on LPS-induced AKI, and it may be a promising therapeutic agent for septic AKI.

scholarly journals C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury

2020 ◽  
Vol 217 (11) ◽  
Author(s):  
Miyako Tanaka ◽  
Marie Saka-Tanaka ◽  
Kozue Ochi ◽  
Kumiko Fujieda ◽  
Yuki Sugiura ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Free Cholesterol ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Sterile Inflammation ◽  
Renal Tubular Cell ◽  
Renal Tubules ◽  
Underlying Mechanisms

Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia–reperfusion injury. Using lipophilic extract from the injured kidney, we identified β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death–triggered, sustained inflammation after acute kidney injury.

MO367USEFULNESS OF ECHOCARDIOGRAPHIC PARAMETERS IN LONG - TERM CARDIOVASCULAR EVENTS AFTER AN ACUTE KIDNEY INJURY EPISODE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Alicia Cabrera ◽  
Laura Salanova Villanueva ◽  
Ana Sanchez ◽  
Patricia Muñoz Ramos ◽  
Pablo Ruano ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Diastolic Dysfunction ◽  
Cardiovascular Events ◽  
Associated Factors ◽  
Systolic Dysfunction ◽  
Kidney Injury ◽  
Epidemiological Data ◽  
Echocardiographic Parameters ◽  
Ventricle Hypertrophy

Abstract Background and Aims Acute kidney injury (AKI), a frequent condition during hospitalizations, leads to an increase morbidity and mortality. Cardiovascular events are one of the most post-AKI studied complications, but the role of the baseline functional and structural cardiac alterations on prognosis has not been widely studied. The aim of the present study is to evaluate the prognostic value of echocardiographic parameters in the incidence of cardiovascular events (CVE) after a hospitalization-acquire AKI. Method In this is retrospective observational cohort study 1255 patients who presented AKI from 2013 to 2014 at our center were included. Baseline epidemiological data, comorbidities and echocardiographic parameters were collected. After discharge, patients were followed (mean 49±28 months) and post-AKI CVE were registered. In addition, new performed echocardiograms after discharge were collected. Associated factors to CVE and the predictive role of echocardiographic parameters were analyzed. Results Among the 1255 included patients, 676 (54%) had a registered echocardiogram in the six months before the AKI episode. Of them, 231 patients (38%) had left ventricle hypertrophy (LVH), 178 (30%) pulmonary hypertension (PHT), 178 (30%) diastolic dysfunction and 138 (21%) systolic dysfunction. After discharge (and prior to post-AKI CVE), 248 (20%) patients had a new echocardiogram that revealed LVH in 108 patients (45%), diastolic dysfunction in 96 (42%), PHT in 68 (32%) and systolic dysfunction in 47 (19%). During follow-up, 484 (39%) patients had CVE. The presence of diastolic dysfunction, systolic dysfunction, PHT and LVH in any moment were associated factors to the incidence of CVE. An adjusted multivariate model showed that systolic dysfunction (hazard ratio [HR] 1.44, 95% confidence interval [95%CI] 1.073-1.943, p=0.015), age (HR 1.018, 95%CI 1.003-1.030, p=0.02), diabetes mellitus (HR 1.373, 95%CI 1.041-1.811, p=0.025), atrial fibrillation (HR 1.397, 95%CI 1.055-1.851, p=0.020) and diuretic intake (HR 1.580, 95%CI 1.171-2.131, p=0.003) were independent predictors of post-AKI CVE. Conclusion The evaluation of cardiac structure and functionality valued by echocardiographic parameters can be a useful tool for stratifying CVE risk after an AKI. Systolic dysfunction is an independent predictor of post-AKI CVE.

scholarly journals Arterial Hypertension and Unusual Ascending Aortic Dilatation in a Neonate With Acute Kidney Injury: Mechanistic Computer Modeling

2019 ◽  
Vol 10 ◽  
Author(s):  
Luis Altamirano-Diaz ◽  
Andrea D. Kassay ◽  
Baran Serajelahi ◽  
Christopher W. McIntyre ◽  
Guido Filler ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Arterial Hypertension ◽  
Computer Modeling ◽  
Kidney Injury ◽  
Aortic Dilatation

scholarly journals Current understanding of the administration of mesenchymal stem cells in acute kidney injury to chronic kidney disease transition: a review with a focus on preclinical models

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Lingfei Zhao ◽  
Fei Han ◽  
Junni Wang ◽  
Jianghua Chen
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Regenerative Process ◽  
Functional Deficits ◽  
Underlying Mechanisms

AbstractIncomplete recovery from acute kidney injury (AKI) can result in long-term functional deficits and has been recognized as a major contributor to chronic kidney disease (CKD), which is termed the AKI-CKD transition. Currently, an effective intervention for this disorder is still lacking. Principally, therapeutic strategies targeting the AKI-CKD transition can be divided into those reducing the severity of AKI or promoting the regenerative process towards beneficially adaptive repair pathways. Considering the fact that mesenchymal stem cells (MSCs) have the potential to address both aspects, therapeutic regimens based on MSCs have a promising future. In light of this information, we focus on the currently available evidence associated with MSC therapy involved in the treatment of the AKI-CKD transition and the underlying mechanisms. All of these discussions will contribute to the establishment of a reliable therapeutic strategy for patients with this problem, who can be easily ignored by physicians, and will lead to a better clinical outcome for them.

scholarly journals NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury

2021 ◽  
Author(s):  
Zhi-yong Xie ◽  
Wei Dong ◽  
Li Zhang ◽  
Meng-jie Wang ◽  
Zhen-meng Xiao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Fibrosis ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Ckd Progression ◽  
Renal Tubulointerstitial Fibrosis ◽  
Underlying Mechanisms

AbstractAcute kidney injury (AKI) with maladaptive tubular repair leads to renal fibrosis and progresses to chronic kidney disease (CKD). At present, there is no curative drug to interrupt AKI-to-CKD progression. The nuclear factor of the activated T cell (NFAT) family was initially identified as a transcription factor expressed in most immune cells and involved in the transcription of cytokine genes and other genes critical for the immune response. NFAT2 is also expressed in renal tubular epithelial cells (RTECs) and podocytes and plays an important regulatory role in the kidney. In this study, we investigated the renoprotective effect of 11R-VIVIT, a peptide inhibitor of NFAT, on renal fibrosis in the AKI-to-CKD transition and the underlying mechanisms. We first examined human renal biopsy tissues and found that the expression of NFAT2 was significantly increased in RTECs in patients with severe renal fibrosis. We then established a mouse model of AKI-to-CKD transition using bilateral ischemia-reperfusion injury (Bi-IRI). The mice were treated with 11R-VIVIT (5 mg/kg, i.p.) on Days 1, 3, 10, 17 and 24 after Bi-IRI. We showed that the expression of NFAT2 was markedly increased in RTECs in the AKI-to-CKD transition. 11R-VIVIT administration significantly inhibited the nuclear translocation of NFAT2 in RTECs, decreased the levels of serum creatinine and blood urea nitrogen, and attenuated renal tubulointerstitial fibrosis but had no toxic side effects on the heart and liver. In addition, we showed that 11R-VIVIT administration alleviated RTEC apoptosis after Bi-IRI. Consistently, preapplication of 11R-VIVIT (100 nM) and transfection with NFAT2-targeted siRNA markedly suppressed TGFβ-induced HK-2 cell apoptosis in vitro. In conclusion, 11R-VIVIT administration inhibits IRI-induced NFAT2 activation and prevents AKI-to-CKD progression. Inhibiting NFAT2 may be a promising new therapeutic strategy for preventing renal fibrosis after IR-AKI.

scholarly journals Preconditioning strategies to prevent acute kidney injury

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 237 ◽  
Author(s):  
Martin Richard Späth ◽  
Felix Carlo Koehler ◽  
Karla Johanna Ruth Hoyer-Allo ◽  
Franziska Grundmann ◽  
Volker Burst ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Calorie Restriction ◽  
Kidney Injury ◽  
Routine Clinical Practice ◽  
Research Strategies ◽  
Clinical Disorder ◽  
Clinical Tools ◽  
Underlying Mechanisms

Acute kidney injury is a common clinical disorder resulting in significantly increased morbidity and mortality. However, despite extensive research, strategies for prevention or treatment are still lacking in routine clinical practice. Already decades ago, several preconditioning strategies (e. g. ischemic/hypoxic preconditioning and calorie restriction) have been published and their extraordinary effectiveness - especially in rodents - has raised the hope for powerful clinical tools to prevent acute kidney injury. However, the underlying mechanisms are still not completely understood and translation to the clinics has not been successful yet. In this review, the most attractive strategies and the current mechanistic concepts are introduced and discussed. Furthermore, we present clinical trials evaluating the feasibility of preconditioning in the clinical setting.

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