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Clinical Journal of the American... May 2015Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are... (Review)
Review
Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal "osmoreceptors" that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance.
Topics: Brain; Cell Size; Diabetes Insipidus; Homeostasis; Humans; Hyponatremia; Kidney Medulla; Kidney Tubules, Collecting; Osmotic Pressure; Sensory Receptor Cells; Thirst; Vasopressins; Water; Water-Electrolyte Balance
PubMed: 25078421
DOI: 10.2215/CJN.10741013 -
JCI Insight Jun 2021Single-cell sequencing studies have characterized the transcriptomic signature of cell types within the kidney. However, the spatial distribution of acute kidney injury...
Single-cell sequencing studies have characterized the transcriptomic signature of cell types within the kidney. However, the spatial distribution of acute kidney injury (AKI) is regional and affects cells heterogeneously. We first optimized coordination of spatial transcriptomics and single-nuclear sequencing data sets, mapping 30 dominant cell types to a human nephrectomy. The predicted cell-type spots corresponded with the underlying histopathology. To study the implications of AKI on transcript expression, we then characterized the spatial transcriptomic signature of 2 murine AKI models: ischemia/reperfusion injury (IRI) and cecal ligation puncture (CLP). Localized regions of reduced overall expression were associated with injury pathways. Using single-cell sequencing, we deconvoluted the signature of each spatial transcriptomic spot, identifying patterns of colocalization between immune and epithelial cells. Neutrophils infiltrated the renal medulla in the ischemia model. Atf3 was identified as a chemotactic factor in S3 proximal tubules. In the CLP model, infiltrating macrophages dominated the outer cortical signature, and Mdk was identified as a corresponding chemotactic factor. The regional distribution of these immune cells was validated with multiplexed CO-Detection by indEXing (CODEX) immunofluorescence. Spatial transcriptomic sequencing complemented single-cell sequencing by uncovering mechanisms driving immune cell infiltration and detection of relevant cell subpopulations.
Topics: Acute Kidney Injury; Animals; Epithelial Cells; Female; Humans; Kidney; Mice; Middle Aged; Reperfusion Injury; Single-Cell Analysis; Transcriptome
PubMed: 34003797
DOI: 10.1172/jci.insight.147703 -
Kidney International Jul 2015The available publications on nephrocalcinosis are wide-ranging and have documented multiple causes and associations of macroscopic or radiological nephrocalcinosis,... (Review)
Review
The available publications on nephrocalcinosis are wide-ranging and have documented multiple causes and associations of macroscopic or radiological nephrocalcinosis, most often located in the renal medulla, with various metabolic and genetic disorders; in fact, so many and various are these that it is difficult to define a common underlying mechanism. We have reviewed nephrocalcinosis in relation to its definition, genetic associations, animal models, and putative mechanisms. We have concluded, and hypothesized, that nephrocalcinosis is primarily a renal interstitial process, resembling metastatic calcification, and that it may have some features in common with, and pathogenic links to, vascular calcification.
Topics: Animals; Calcium; Calcium Oxalate; Calcium Phosphates; Disease Models, Animal; Homeostasis; Humans; Kidney Tubules; Nephrocalcinosis
PubMed: 25807034
DOI: 10.1038/ki.2015.76 -
Nature Communications Jul 2023Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal...
Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.
Topics: Humans; Kidney Medulla; Matrix Metalloproteinase 9; Matrix Metalloproteinase 7; Calcium Oxalate; Transcriptome; Kidney Calculi
PubMed: 37468493
DOI: 10.1038/s41467-023-38975-8 -
Kidney Diseases (Basel, Switzerland) Mar 2016SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the... (Review)
Review
BACKGROUND
SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology.
SUMMARY
SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity. With regard to the kidney, SIRT1 attenuates diabetic albuminuria, reduces blood pressure and related cardiovascular diseases, resists acute kidney injury, delays kidney fibrogenesis, promotes cyst formation and benefits renal ageing.
KEY MESSAGES
This review summarizes the biology of SIRT1 and focuses on the latest studies concerning SIRT1 as a potential therapeutic target for kidney diseases.
PubMed: 27536685
DOI: 10.1159/000440967 -
Anatomical Record (Hoboken, N.J. : 2007) Oct 2020Per gram of tissue, the kidneys are among our most highly perfused organs. Yet the renal cortex and, in particular, the renal medulla are susceptible to hypoxia. In... (Review)
Review
Per gram of tissue, the kidneys are among our most highly perfused organs. Yet the renal cortex and, in particular, the renal medulla are susceptible to hypoxia. In turn, hypoxia is a major pathophysiological feature of both acute kidney injury and chronic kidney disease. We identify seven factors that render the kidney susceptible to hypoxia: (1) the large metabolic demand imposed by active reabsorption of sodium; (2) limitations on oxygen delivery to cortical tissue imposed by the density of peritubular capillaries; (3) the poor capacity for angiogenesis in the adult kidney; (4) the limited ability of the renal vasculature to dilate in response to hypoxia; (5) diffusive oxygen shunting between arteries and veins in the cortex and descending and ascending vasa recta in the medulla; (6) the physiological requirement for low medullary blood flow to facilitate urinary concentration; and (7) the topography of vascular-tubular arrangements in the outer medulla that limit oxygen delivery to the thick ascending limb of Henle's loop. Recent collaborative efforts between anatomists, physiologists, and mathematicians have improved our understanding of the roles of these factors in both physiological regulation of intrarenal oxygenation and development of renal hypoxia under pathophysiological conditions. We are also better able to understand these apparent maladaptations in the context of evolution. That is, they can be explained by the combined effects of historical contingency (our ancestral life in the sea) and selection pressures imposed by the multiple functions of the kidney to regulate extracellular fluid volume, retain water, and control erythrocyte production.
Topics: Animals; Hemodynamics; Humans; Hypoxia; Kidney; Vasodilation
PubMed: 31566903
DOI: 10.1002/ar.24260 -
Frontiers in Bioscience (Scholar... Jun 2016Anandamide (AEA) is the N-acyl ethanolamide of arachidonic acid, an agonist of cannabinoid and non-cannabinoid receptors in the body. The kidneys are enriched in AEA and... (Review)
Review
Anandamide (AEA) is the N-acyl ethanolamide of arachidonic acid, an agonist of cannabinoid and non-cannabinoid receptors in the body. The kidneys are enriched in AEA and in enzymes that metabolize AEA, but the roles of AEA and its metabolites in the kidney remain poorly understood. This system likely is involved in the regulation of renal blood flow and hemodynamics and of tubular sodium and fluid reabsorption. It may act as a neuromodulator of the renal sympathetic nervous system. AEA and its cyclooxygenase-2 metabolites, the prostamides, in the renal medulla may represent a unique antihypertensive system involved in the long-term control of blood pressure. AEA and its metabolites are also implicated as modulators of inflammation and mediators of signaling in inflammation. AEA and its metabolites may be influential in chronic kidney disease states associated with inflammation and cardiovascular diseases associated with hyperhomocysteinemia. The current knowledge of the roles of AEA and its derivatives highlights the need for further research to define and potentially exploit the role of this endocannabinoid system in the kidney.
Topics: Animals; Arachidonic Acids; Endocannabinoids; Humans; Kidney; Polyunsaturated Alkamides; Signal Transduction
PubMed: 27100705
DOI: 10.2741/s461 -
Seminars in Nephrology Mar 2020The kidney is a highly metabolic organ that requires substantial adenosine triphosphate for the active transport required to maintain water and solute reabsorption.... (Review)
Review
The kidney is a highly metabolic organ that requires substantial adenosine triphosphate for the active transport required to maintain water and solute reabsorption. Aberrations in energy availability and energy utilization can lead to cellular dysfunction and death. Mitochondria are essential for efficient energy production. The pathogenesis of acute kidney injury is complex and varies with different types of injury. However, multiple distinct acute kidney injury syndromes share a common dysregulation of energy metabolism. Pathways of energy metabolism and mitochondrial dysfunction are emerging as critical drivers of acute kidney injury and represent new potential targets for treatment. This review shows the basic metabolic pathways that all cells depend on for life; describes how the kidney optimizes those pathways to meet its anatomic, physiologic, and metabolic needs; summarizes the importance of metabolic and mitochondrial dysfunction in acute kidney injury; and analyzes the mitochondrial processes that become dysregulated in acute kidney injury including mitochondrial dynamics, mitophagy, mitochondrial biogenesis, and changes in mitochondrial energy metabolism.
Topics: Acute Kidney Injury; Animals; Energy Metabolism; Humans; Kidney; Kidney Cortex; Kidney Medulla; Metabolic Networks and Pathways; Mitochondria; Mitochondrial Dynamics; Mitophagy; Nephrons; Organelle Biogenesis
PubMed: 32303274
DOI: 10.1016/j.semnephrol.2020.01.002 -
Archives of Pathology & Laboratory... Sep 2021Renal malignancies can be divided into cortical- and medullary-based tumors, the latter of which classically infiltrate the renal parenchyma by extending between... (Review)
Review
CONTEXT.—
Renal malignancies can be divided into cortical- and medullary-based tumors, the latter of which classically infiltrate the renal parenchyma by extending between nonneoplastic structures. Although high-grade cortical tumors can rarely exhibit the same growth pattern, the infiltrative morphology should elicit a differential diagnosis to be considered in each case. However, these diagnoses can be challenging to distinguish, especially on small renal biopsy samples.
OBJECTIVE.—
To provide an overview of the clinical, gross, and microscopic findings; genetic and molecular alterations; and immunohistochemical evaluation of medullary-based renal tumors and other tumor types with overlapping morphologies and growth patterns.
DATA SOURCES.—
Literature review and personal observations were used to compile the information in this review.
CONCLUSIONS.—
Collecting duct carcinoma is a prototypical medullary-based tumor, and although diagnostic criteria exist, it remains a diagnosis of exclusion, especially with ancillary techniques aiding the recognition of established as well as more recently described neoplasms. Other medullary-based malignancies included in the differential diagnosis include renal medullary carcinoma/renal cell carcinoma unclassified with medullary phenotype, fumarate hydratase-deficient renal cell carcinoma, and upper tract urothelial carcinoma. Moreover, other rare entities should be excluded, including metastatic carcinoma, lymphoma, and melanoma. In addition to potential prognostic differences, accurate diagnoses can have important surgical and clinical management implications.
Topics: Diagnosis, Differential; Humans; Kidney Medulla; Kidney Neoplasms
PubMed: 33406251
DOI: 10.5858/arpa.2020-0464-RA