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BioMed Research International 2018Detoxification is a fundamental function for all living organisms that need to excrete catabolites and toxins to maintain homeostasis. Kidneys are major organs of... (Review)
Review
Detoxification is a fundamental function for all living organisms that need to excrete catabolites and toxins to maintain homeostasis. Kidneys are major organs of detoxification that maintain water and electrolyte balance to preserve physiological functions of vertebrates. In insects, the renal function is carried out by Malpighian tubules and nephrocytes. Due to differences in their circulation, the renal systems of mammalians and insects differ in their functional modalities, yet carry out similar biochemical and physiological functions and share extensive genetic and molecular similarities. Evolutionary conservation can be leveraged to model specific aspects of the complex mammalian kidney function in the genetic powerhouse to study how genes interact in diseased states. Here, we compare the human and renal systems and present selected fly disease models.
Topics: Animals; Disease Models, Animal; Drosophila Proteins; Drosophila melanogaster; Humans; Kidney; Kidney Diseases; Malpighian Tubules
PubMed: 29955604
DOI: 10.1155/2018/5697436 -
Nephron 2018Acute kidney injury (AKI) is a major clinical problem in native and transplanted kidneys. Bidirectional interaction between gut microbiota and kidney tissue or the... (Review)
Review
Acute kidney injury (AKI) is a major clinical problem in native and transplanted kidneys. Bidirectional interaction between gut microbiota and kidney tissue or the "colo-renal" system is being recognized as an important modulating factor in AKI. Gut microbes appear to have a complex but yet poorly understood communication with renal cellular and molecular processes that affect normal kidney function and response to injury. There have been major recent advances in the study of the microbiome that provide an opportunity to apply this knowledge to improve our understanding and treatment of patients with AKI. This mini-review aims to focus on select general concepts about the microbiome, mechanisms by which the microbiome can modify kidney function, and data on microbiome and AKI. We have briefly touched on a few topics rather than comprehensively reviewing the role of microbiome in kidney diseases. We also propose future gut microbiota-AKI studies based on advances in gut microbiota studies in other human diseases and experimental models.
Topics: Acute Kidney Injury; Gastrointestinal Microbiome; Humans; Microbiota
PubMed: 29961049
DOI: 10.1159/000490392 -
Cells Jul 2020The kidney is essential for systemic calcium homeostasis. Urinary calcium excretion can be viewed as an integrative renal response to endocrine and local stimuli. The... (Review)
Review
The kidney is essential for systemic calcium homeostasis. Urinary calcium excretion can be viewed as an integrative renal response to endocrine and local stimuli. The extracellular calcium-sensing receptor (CaSR) elicits a number of adaptive reactions to increased plasma Ca levels including the control of parathyroid hormone release and regulation of the renal calcium handling. Calcium reabsorption in the distal nephron of the kidney is functionally coupled to sodium transport. Apart from Ca transport systems, CaSR signaling affects relevant distal Na-(K)-2Cl cotransporters, NKCC2 and NCC. NKCC2 and NCC are activated by a kinase cascade comprising with-no-lysine [K] kinases (WNKs) and two homologous Ste20-related kinases, SPAK and OSR1. Gain-of-function mutations within the WNK-SPAK/OSR1-NKCC2/NCC pathway lead to renal salt retention and hypertension, whereas loss-of-function mutations have been associated with salt-losing tubulopathies such as Bartter or Gitelman syndromes. A Bartter-like syndrome has been also described in patients carrying gain-of-function mutations in the CaSR gene. Recent work suggested that CaSR signals via the WNK-SPAK/OSR1 cascade to modulate salt reabsorption along the distal nephron. The review presented here summarizes the latest progress in understanding of functional interactions between CaSR and WNKs and their potential impact on the renal salt handling and blood pressure.
Topics: Animals; Humans; Kidney; Nephrons; Protein Serine-Threonine Kinases; Receptors, Calcium-Sensing; Signal Transduction
PubMed: 32659887
DOI: 10.3390/cells9071644 -
Nature Communications Sep 2023The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear....
The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
Topics: Adult; Humans; Causality; Methylamines; Endocrinology; Kidney
PubMed: 37730687
DOI: 10.1038/s41467-023-39824-4 -
The Journal of Physiology Jun 2021This review summarizes the newly discovered molecular mechanism of secretin-stimulated urine HCO excretion and the role of cystic fibrosis transmembrane conductance... (Review)
Review
This review summarizes the newly discovered molecular mechanism of secretin-stimulated urine HCO excretion and the role of cystic fibrosis transmembrane conductance regulator (CFTR) in renal HCO excretion. The secretin receptor is functionally expressed in the basolateral membrane of the HCO -secreting β-intercalated cells of the collecting duct. Here it activates a fast and efficient secretion of HCO into the urine serving to normalize metabolic alkalosis. The ability to acutely increase renal base excretion is entirely dependent on functional pendrin (SLC26A4) and CFTR, and both proteins localize to the apical membrane of the β-intercalated cells. In cystic fibrosis mice and patients, this function is absent or markedly reduced. We discuss that the alkaline tide, namely the transient urine alkalinity after a meal, has now received a clear physiological explanation.
Topics: Animals; Bicarbonates; Chloride-Bicarbonate Antiporters; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Mice; Secretin; Sulfate Transporters
PubMed: 33963548
DOI: 10.1113/JP281285 -
Frontiers in Physiology 2020The Barker hypothesis strongly supported the influence of fetal environment on the development of chronic diseases in later life. Multiple experimental and human studies... (Review)
Review
The Barker hypothesis strongly supported the influence of fetal environment on the development of chronic diseases in later life. Multiple experimental and human studies have identified that the deleterious effect of fetal programming commonly leads to alterations in renal development. The interplay between environmental insults and fetal genome can induce epigenetic changes and lead to alterations in the expression of renal phenotype. In this review, we have explored the renal development and its functions, while focusing on the epigenetic findings and functional aspects of the renin-angiotensin system and its components.
PubMed: 33101064
DOI: 10.3389/fphys.2020.586290 -
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 -
Clinical Journal of the American... Oct 2015Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated... (Review)
Review
Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial renin- and erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium.
Topics: Adenosine; Anemia; Animals; Erythropoietin; Fibroblasts; Humans; Kidney; Kidney Diseases; Mesenchymal Stem Cells; Neural Crest; Renin; Renin-Angiotensin System
PubMed: 25813241
DOI: 10.2215/CJN.00640114 -
Journal of the American Society of... Sep 2021Tissue-resident memory T (T) cells are known to be important for the first line of defense in mucosa-associated tissues. However, the composition, localization, effector...
BACKGROUND
Tissue-resident memory T (T) cells are known to be important for the first line of defense in mucosa-associated tissues. However, the composition, localization, effector function, and specificity of T cells in the human kidney and their relevance for renal pathology have not been investigated.
METHODS
Lymphocytes derived from blood, renal peritumor samples, and tumor samples were phenotypically and functionally assessed by applying flow cytometry and highly advanced histology (multi-epitope ligand cartography) methods.
RESULTS
CD69CD103CD8 T cells in kidneys display an inflammatory profile reflected by enhanced IL-2, IL-17, and TNF production, and their frequencies correlate with increasing age and kidney function. We further identified mucosa-associated invariant T and CD56 and CD56 natural killer cells likewise expressing CD69 and CD103, the latter significantly enriched in renal tumor tissues. CD8 T cell frequencies were not elevated in kidney tumor tissue, but they coexpressed PD-1 and TOX and produced granzyme B. Tumor-derived CD8 T cells from patients with metastases were functionally impaired. Both CD69CD103CD4 and CD69CD103CD8 T cells form distinct clusters in tumor tissues in proximity to antigen-presenting cells. Finally, EBV, CMV, BKV, and influenza antigen-specific CD8 T cells were enriched in the effector memory T cell population in the kidney.
CONCLUSIONS
Our data provide an extensive overview of T cells' phenotypes and functions in the human kidney for the first time, pointing toward their potential relevance in kidney transplantation and kidney disease.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Differentiation, T-Lymphocyte; Female; Germany; Humans; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Phenotype; T-Lymphocytes
PubMed: 34074699
DOI: 10.1681/ASN.2020101528 -
Advances in Physiology Education Dec 2009The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure.... (Review)
Review
The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and tubular epithelial cell sodium chloride and water transport mechanisms. Pharmacological inhibition of the actions of the RAS are widely used in the treatment of patients with hypertension, congestive heart failure, left ventricular dysfunction, pulmonary and systemic edema, diabetic nephropathy, cirrhosis of the liver, scleroderma, and migraines. Therefore, a thorough understanding of the influences of the RAS on normal renal physiology is of major importance for first-year medical students.
Topics: Animals; Humans; Physiology; Renal Circulation; Renal Insufficiency; Renin-Angiotensin System
PubMed: 19948673
DOI: 10.1152/advan.00049.2009