Kidney vascular congestion exacerbates acute kidney injury in mice

Kitani, Takashi; Kidokoro, Kengo; Nakata, Tomohiro; Kirita, Yuhei; Nakamura, Itaru; Nakai, Kunihiro; Yagi-Tomita, Aya; Ida, Tomoharu; Uehara-Watanabe, Noriko; Ikeda, Kisho; Yamashita, Nobuhiko; Humphreys, Benjamin D.; Kashihara, Naoki; Matoba, Satoaki; Tamagaki, Keiichi; Kusaba, Tetsuro

doi:10.1016/j.kint.2021.11.015

Cited by 13 publications

(8 citation statements)

References 47 publications

(51 reference statements)

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“…During the late time point these proliferative cells almost disappeared and another cluster related to inflammation and fibrosis appeared. These cells upregulated Pdgfd, Kcnip4, Vcam1 and Ccl2, all known markers for fibrosis and inflammation ( Seron et al, 1991 ; Ostendorf et al, 2012 ; Kirita et al, 2020 ), while pathway analysis showed activation of AP-1 and NF-kB pathways, both pathways that have been identified previously to play an important role in driving kidney fibrosis after AKI ( Liu et al, 2014 ; Ferenbach and Bonventre, 2015 ; Nakagawa et al, 2016 ; Kitani et al, 2022 ). Based on that, these cells were named maladaptive PTs.…”

Section: Introductionmentioning

confidence: 66%

What We Have Learned so far From Single Cell Sequencing in Acute Kidney Injury

Buse

Moeller²,

Stamellou³

2022

Front. Physiol.

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Acute Kidney injury is a major clinical problem associated with increased morbidity and mortality. Despite, intensive research the clinical outcome remains poor and apart from supportive therapy no other specific therapy exists. Single cell technologies have enabled us to get deeper insights into the transcriptome of individual cells in complex tissues like the kidney. With respect to kidney injury, this would allow us to better define the unique role of individual cell populations in the pathophysiology of acute kidney injury and progression to chronic kidney disease. In this mini review, we would like to give an overview and discuss the current major findings in the field of acute kidney injury through Single-Cell technologies.

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Section: Introductionmentioning

confidence: 66%

What We Have Learned so far From Single Cell Sequencing in Acute Kidney Injury

Buse

Moeller²,

Stamellou³

2022

Front. Physiol.

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Section: Pathophysiologymentioning

confidence: 99%

“…Venous congestion may stimulate upregulation of fibrotic pathways in the kidney and also activate endothelial cells to release local neurohormones and cytokines, which will propagate inflammatory pathways. [15][16][17] In some patients with acute decompensated heart failure, congestion can manifest as ascites with increased intra-abdominal pressure. Among 40 patients admitted for acute decompensated heart failure, with comparable hemodynamics, those with elevated intra-abdominal pressures of $8 mm Hg had higher baseline serum creatinine (2.361.0 mg/dl versus 1.560.8 mg/dl).…”

Section: Venous Congestionmentioning

confidence: 99%

Cardiorenal Syndrome in the Hospital

McCallum

Sarnak

2023

CJASN

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The cardiorenal syndrome refers to a group of complex, bidirectional pathophysiological pathways involving dysfunction in both the heart and kidney. Upward of 60% of patients admitted for acute decompensated heart failure have CKD, as defined by an eGFR of <60 ml/min per 1.73 m2. CKD, in turn, is one of the strongest risk factors for mortality and cardiovascular events in acute decompensated heart failure. Although not well understood, the mechanisms in the cardiorenal syndrome include venous congestion, arterial underfilling, neurohormonal activation, inflammation, and endothelial dysfunction. Arterial underfilling may lead to activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, leading to sodium reabsorption and vasoconstriction. Venous congestion likely also mediates and perpetuates these maladaptive pathways. To rule out intrinsic kidney disease that is distinct from the cardiorenal syndrome, one should obtain a careful history, review longitudinal eGFR trends, assess albuminuria and proteinuria, and review the urine sediment and kidney imaging. The hallmark of the cardiorenal syndrome is intense sodium avidity and diuretic resistance, often requiring a combination of diuretics with varying pharmacological targets, and monitoring of urinary response to guide escalations in therapy. Invasive means of decongestion may be required including ultrafiltration or kidney RRT such as peritoneal dialysis, which is often better tolerated from a hemodynamic perspective than intermittent hemodialysis. Strategies for increasing forward perfusion in states of low cardiac output and cardiogenic shock may include afterload reduction and inotropes and, in the most severe cases, mechanical circulatory support devices, many of which have kidney-specific considerations.

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“…The contribution of renal venous congestion to renal dysfunction in HF is complex, involving multiple contributing mechanisms ( Figure 2 ) ( 7 ). Increased renal venous pressure increases pressures along the renal vascular tree, thus decreasing RBF ( 207 ) and arteriovenous pressure gradient in the glomerulus and thereby decreasing GFR ( 7 ).…”

Section: Mechanisms Underlying Edema Formationmentioning

confidence: 99%

Edema formation in congestive heart failure and the underlying mechanisms

Abassi

Khoury

Karram

et al. 2022

Front. Cardiovasc. Med.

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Congestive heart failure (HF) is a complex disease state characterized by impaired ventricular function and insufficient peripheral blood supply. The resultant reduced blood flow characterizing HF promotes activation of neurohormonal systems which leads to fluid retention, often exhibited as pulmonary congestion, peripheral edema, dyspnea, and fatigue. Despite intensive research, the exact mechanisms underlying edema formation in HF are poorly characterized. However, the unique relationship between the heart and the kidneys plays a central role in this phenomenon. Specifically, the interplay between the heart and the kidneys in HF involves multiple interdependent mechanisms, including hemodynamic alterations resulting in insufficient peripheral and renal perfusion which can lead to renal tubule hypoxia. Furthermore, HF is characterized by activation of neurohormonal factors including renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), endothelin-1 (ET-1), and anti-diuretic hormone (ADH) due to reduced cardiac output (CO) and renal perfusion. Persistent activation of these systems results in deleterious effects on both the kidneys and the heart, including sodium and water retention, vasoconstriction, increased central venous pressure (CVP), which is associated with renal venous hypertension/congestion along with increased intra-abdominal pressure (IAP). The latter was shown to reduce renal blood flow (RBF), leading to a decline in the glomerular filtration rate (GFR). Besides the activation of the above-mentioned vasoconstrictor/anti-natriuretic neurohormonal systems, HF is associated with exceptionally elevated levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). However, the supremacy of the deleterious neurohormonal systems over the beneficial natriuretic peptides (NP) in HF is evident by persistent sodium and water retention and cardiac remodeling. Many mechanisms have been suggested to explain this phenomenon which seems to be multifactorial and play a major role in the development of renal hyporesponsiveness to NPs and cardiac remodeling. This review focuses on the mechanisms underlying the development of edema in HF with reduced ejection fraction and refers to the therapeutic maneuvers applied today to overcome abnormal salt/water balance characterizing HF.

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Kidney vascular congestion exacerbates acute kidney injury in mice

Cited by 13 publications

References 47 publications

What We Have Learned so far From Single Cell Sequencing in Acute Kidney Injury

What We Have Learned so far From Single Cell Sequencing in Acute Kidney Injury

Cardiorenal Syndrome in the Hospital

Edema formation in congestive heart failure and the underlying mechanisms

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