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Advances in Chronic Kidney Disease May 2020Chronic kidney disease (CKD) is a major noncommunicable disorder and has become the 9th leading cause of death in the United States. Most patients with CKD in the United... (Review)
Review
Chronic kidney disease (CKD) is a major noncommunicable disorder and has become the 9th leading cause of death in the United States. Most patients with CKD in the United States choose hemodialysis as their treatment of choice. A functioning arteriovenous access is essential to reduce dependence on central venous catheters. An arteriovenous fistula (AVF), though the preferred access, has a major limitation with a high primary maturation failure rate. A functioning AVF requires well-preserved vessels, both arteries and veins, along with an acceptable cardiac pump function. Vessel preservation is crucial from a surgeon's perspective to create an AVF but is also relevant for maturation. More recently, concerns regarding the sequelae of transradial approach for percutaneous cardiac interventions have been raised. Educating and empowering the patient is the first step, but equally important is to educate all caregivers involved in providing care to a patient with advanced CKD. The current review evaluates the strategies used to preserve peripheral veins, central veins, and peripheral arteries.
Topics: Arteriovenous Shunt, Surgical; Blood Vessels; Catheterization, Central Venous; Humans; Regional Blood Flow; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Access Devices; Vascular System Injuries
PubMed: 32891300
DOI: 10.1053/j.ackd.2020.03.006 -
Journal of the American Society of... May 2020Expression of SerpinB2, a regulator of inflammatory processes, has been described in the context of macrophage activation and cellular senescence. Given that mechanisms...
BACKGROUND
Expression of SerpinB2, a regulator of inflammatory processes, has been described in the context of macrophage activation and cellular senescence. Given that mechanisms for these processes interact and can shape kidney disease, it seems plausible that SerpinB2 might play a role in renal aging, injury, and repair.
METHODS
We subjected SerpinB2 knockout mice to ischemia-reperfusion injury or unilateral ureteral obstruction. We performed phagocyte depletion to study SerpinB2's role beyond the effects of macrophages and transplanted bone marrow from knockout mice to wild-type mice and to dissect cell type-dependent effects. Primary tubular cells and macrophages from SerpinB2 knockout and wild-type mice were used for functional studies and transcriptional profiling.
RESULTS
Cultured senescent tubular cells, kidneys of aged mice, and renal stress models exhibited upregulation of SerpinB2 expression. Functionally, lack of SerpinB2 in aged knockout mice had no effect on the magnitude of senescence markers but associated with enhanced kidney damage and fibrosis. In stress models, inflammatory cell infiltration was initially lower in knockout mice but later increased, leading to an accumulation of significantly more macrophages. SerpinB2 knockout tubular cells showed significantly reduced expression of the chemokine CCL2. Macrophages from knockout mice exhibited reduced phagocytosis and enhanced migration. Macrophage depletion and bone marrow transplantation experiments validated the functional relevance of these cell type-specific functions of SerpinB2.
CONCLUSIONS
SerpinB2 influences tubule-macrophage crosstalk by supporting tubular CCL2 expression and regulating macrophage phagocytosis and migration. In mice, SerpinB2 expression seems to be needed for coordination and timely resolution of inflammation, successful repair, and kidney homeostasis during aging. Implications of SerpinB2 in human kidney disease deserve further exploration.
Topics: Acute Kidney Injury; Aging; Animals; Cell Movement; Cellular Senescence; Chemokine CCL2; Coculture Techniques; Enzyme Induction; Epithelial Cells; Fibrosis; Homeostasis; Kidney; Kidney Tubules; Macrophages; Male; Mice; Mice, Knockout; Phagocytosis; Plasminogen Activator Inhibitor 2; Reperfusion Injury; Transcriptome; Ureteral Obstruction
PubMed: 32209589
DOI: 10.1681/ASN.2019101085 -
Hypertension Research : Official... Oct 2022Renalase is a ~38 kDa flavin-adenine dinucleotide (FAD) domain-containing protein that can function as a cytokine and an anomerase. It is emerging as a novel regulator... (Review)
Review
Renalase is a ~38 kDa flavin-adenine dinucleotide (FAD) domain-containing protein that can function as a cytokine and an anomerase. It is emerging as a novel regulator of cardiometabolic diseases. Expressed mainly in the kidneys, renalase has been reported to have a hypotensive effect and may control blood pressure through regulation of sympathetic tone. Furthermore, genetic variations in the renalase gene, such as a functional missense polymorphism (Glu37Asp), have implications in the cardiovascular and renal systems and can potentially increase the risk of cardiometabolic disorders. Research on the physiological functions and biochemical actions of renalase over the years has indicated a role for renalase as one of the key proteins involved in various disease states, such as diabetes, impaired lipid metabolism, and cancer. Recent studies have identified three transcription factors (viz., Sp1, STAT3, and ZBP89) as key positive regulators in modulating the expression of the human renalase gene. Moreover, renalase is under the post-transcriptional regulation of two microRNAs (viz., miR-29b, and miR-146a), which downregulate renalase expression. While renalase supplementation may be useful for treating hypertension, inhibition of renalase signaling may be beneficial to patients with cancerous tumors. However, more incisive investigations are required to unravel the potential therapeutic applications of renalase. Based on the literature pertaining to the function and physiology of renalase, this review attempts to consolidate and comprehend the role of renalase in regulating cardiometabolic and renal disorders.
Topics: Humans; Hypertension; Kidney Diseases; MicroRNAs; Monoamine Oxidase
PubMed: 35941358
DOI: 10.1038/s41440-022-00986-1 -
Cell Chemical Biology Jul 2021Nature takes advantage of induced proximity to perform various functions. Taking inspiration from nature, we can also trigger desired biological processes using... (Review)
Review
Nature takes advantage of induced proximity to perform various functions. Taking inspiration from nature, we can also trigger desired biological processes using bifunctional small molecules that artificially induce proximity. For example, bifunctional small molecules have been designed to trigger the ubiquitin-dependent proteasomal degradation of intracellular proteins. Now, recent classes of bifunctional compounds have been developed to degrade extracellular targets, membrane proteins, damaged organelles, and RNA by recruiting alternative degradation pathways. In addition to inducing degradation, bifunctional modalities can change phosphorylation and glycosylation states to evoke a biological response. In this review, we highlight recent advances in these innovative classes of compounds that build on a rich history of chemical inducers of dimerization. We anticipate that more bifunctional molecules, which induce or remove posttranslational modifications, to endow neo-functionalities will emerge.
Topics: Humans; Proteins; RNA
PubMed: 34270935
DOI: 10.1016/j.chembiol.2021.06.005 -
Clinical Journal of the American... Jul 2019
Topics: Adaptation, Psychological; Caregivers; Cognition; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 31248949
DOI: 10.2215/CJN.05870519 -
Medical Image Analysis Apr 2021Assessment of renal function and structure accurately remains essential in the diagnosis and prognosis of Chronic Kidney Disease (CKD). Advanced imaging, including... (Review)
Review
Assessment of renal function and structure accurately remains essential in the diagnosis and prognosis of Chronic Kidney Disease (CKD). Advanced imaging, including Magnetic Resonance Imaging (MRI), Ultrasound Elastography (UE), Computed Tomography (CT) and scintigraphy (PET, SPECT) offers the opportunity to non-invasively retrieve structural, functional and molecular information that could detect changes in renal tissue properties and functionality. Currently, the ability of artificial intelligence to turn conventional medical imaging into a full-automated diagnostic tool is widely investigated. In addition to the qualitative analysis performed on renal medical imaging, texture analysis was integrated with machine learning techniques as a quantification of renal tissue heterogeneity, providing a promising complementary tool in renal function decline prediction. Interestingly, deep learning holds the ability to be a novel approach of renal function diagnosis. This paper proposes a survey that covers both qualitative and quantitative analysis applied to novel medical imaging techniques to monitor the decline of renal function. First, we summarize the use of different medical imaging modalities to monitor CKD and then, we show the ability of Artificial Intelligence (AI) to guide renal function evaluation from segmentation to disease prediction, discussing how texture analysis and machine learning techniques have emerged in recent clinical researches in order to improve renal dysfunction monitoring and prediction. The paper gives a summary about the role of AI in renal segmentation.
Topics: Artificial Intelligence; Humans; Image Processing, Computer-Assisted; Machine Learning; Magnetic Resonance Imaging; Renal Insufficiency, Chronic
PubMed: 33517241
DOI: 10.1016/j.media.2021.101960 -
American Journal of Physiology. Renal... Mar 2024Circadian rhythms are endogenous biological oscillations that regulate various physiological processes in organisms, including kidney function. The kidney plays a vital... (Review)
Review
Circadian rhythms are endogenous biological oscillations that regulate various physiological processes in organisms, including kidney function. The kidney plays a vital role in maintaining homeostasis by regulating water and electrolyte balance, blood pressure, and excretion of metabolic waste products, all of which display circadian rhythmicity. For this reason, studying the circadian regulation of the kidney is important, and the time of day is a biological and experimental variable that must be considered. Over the past decade, considerable progress has been made in understanding the molecular mechanisms underlying circadian regulation within the kidney. In this review, the current knowledge regarding circadian rhythms in the kidney is explored, focusing on the molecular clock machinery, circadian control of renal functions, and the impact of disrupted circadian rhythms on kidney health. In addition, parameters that should be considered and future directions are outlined in this review.
Topics: Circadian Clocks; Kidney; Circadian Rhythm; Water-Electrolyte Balance; Homeostasis
PubMed: 38174377
DOI: 10.1152/ajprenal.00214.2023 -
American Journal of Physiology. Renal... Nov 2019The mammalian circadian clock governs physiological, endocrine, and metabolic responses coordinated in a 24-h rhythmic pattern by the suprachiasmatic nucleus (SCN) of... (Review)
Review
The mammalian circadian clock governs physiological, endocrine, and metabolic responses coordinated in a 24-h rhythmic pattern by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The SCN also dictates circadian rhythms in peripheral tissues like the kidney. The kidney has several important physiological functions, including removing waste and filtering the blood and regulating fluid volume, blood osmolarity, blood pressure, and Ca metabolism, all of which are under tight control of the molecular/circadian clock. Normal aging has a profound influence on renal function, central and peripheral circadian rhythms, and the sleep-wake cycle. Disrupted circadian rhythms in the kidney as a result of increased age likely contribute to adverse health outcomes such as nocturia, hypertension, and increased risk for stroke, cardiovascular disease, and end organ failure. Regular physical activity improves circadian misalignment in both young and old mammals, although the precise mechanisms for this protection remain poorly described. Recent advances in the heart and skeletal muscle literature suggest that regular endurance exercise entrains peripheral clocks, and we propose that similar beneficial adaptations occur in the kidney through regulation of renal blood flow and fluid balance.
Topics: Adaptation, Physiological; Biological Clocks; Exercise; Humans; Kidney; Muscle, Skeletal; Water-Electrolyte Balance
PubMed: 31461350
DOI: 10.1152/ajprenal.00301.2019 -
Advances in Anatomy, Embryology, and... 2021Placenta forms as a momentary organ inside the uterus with a slew of activities only when the woman is pregnant. It is a discoid-shaped hybrid structure consisting of...
Placenta forms as a momentary organ inside the uterus with a slew of activities only when the woman is pregnant. It is a discoid-shaped hybrid structure consisting of maternal and embryonic components. It develops in the mesometrial side of the uterus following blastocyst implantation to keep the two genetically different entities, the mother and embryo, separated but connected. The beginning and progression of placental formation and development following blastocyst implantation coincides with the chronological developmental stages of the embryo. It gradually acquires the ability to perform the vascular, respiratory, hepatic, renal, endocrine, gastrointestinal, immune, and physical barrier functions synchronously that are vital for fetal development, growth, and safety inside the maternal environment. The uterus ejects the placenta when its embryonic growth and survival supportive roles are finished; that is usually the birth of the baby. Despite its irreplaceable role in fetal development and survival over the post-implantation progression of pregnancy, it still remains unclear how it forms, matures, performs all of its activities, and starts to fail functioning. Thus, a detailed understanding about normal developmental, structural, and functional aspects of the placenta may lead to avoid pregnancy problems that arise with the placenta.
Topics: Animals; Embryo Implantation; Female; Humans; Mice; Placenta; Pregnancy; Uterus
PubMed: 34694483
DOI: 10.1007/978-3-030-77360-1_10 -
Frontiers in Integrative Neuroscience 2022Chronic kidney disease (CKD) is a multifactorial pathology that progressively leads to the deterioration of metabolic functions and results from deficient glomerular... (Review)
Review
Chronic kidney disease (CKD) is a multifactorial pathology that progressively leads to the deterioration of metabolic functions and results from deficient glomerular filtration and electrolyte imbalance. Its economic impact on public health is challenging. Mexico has a high prevalence of CKD that is strongly associated with some of the most common metabolic disorders like diabetes and hypertension. The gradual loss of kidney functions provokes an inflammatory state and endocrine alterations affecting several systems. High serum levels of prolactin have been associated with CKD progression, inflammation, and olfactory function. Also, the nutritional status is altered due to impaired renal function. The decrease in calorie and protein intake is often accompanied by malnutrition, which can be severe at advanced stages of the disease. Nutrition and olfactory functioning are closely interconnected, and CKD patients often complain of olfactory deficits, which ultimately can lead to deficient food intake. CKD patients present a wide range of deficits in olfaction like odor discrimination, identification, and detection threshold. The chronic inflammatory status in CKD damages the olfactory epithelium leading to deficiencies in the chemical detection of odor molecules. Additionally, the decline in cognitive functioning impairs the capacity of odor differentiation. It is not clear whether peritoneal dialysis and hemodialysis improve the olfactory deficits, but renal transplants have a strong positive effect. In the present review, we discuss whether the olfactory deficiencies caused by CKD are the result of the induced inflammatory state, the hyperprolactinemia, or a combination of both.
PubMed: 35173591
DOI: 10.3389/fnint.2022.763986