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Seminars in Cell & Developmental Biology Jul 2019The kidney vasculature has a unique and complex architecture that is central for the kidney to exert its multiple and essential physiological functions with the ultimate... (Review)
Review
The kidney vasculature has a unique and complex architecture that is central for the kidney to exert its multiple and essential physiological functions with the ultimate goal of maintaining homeostasis. An appropriate development and coordinated assembly of the different vascular cell types and their association with the corresponding nephrons is crucial for the generation of a functioning kidney. In this review we provide an overview of the renal vascular anatomy, histology, and current knowledge of the embryological origin and molecular pathways involved in its development. Understanding the cellular and molecular mechanisms involved in renal vascular development is the first step to advance the field of regenerative medicine.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Kidney; Neovascularization, Physiologic; Nephrons; Regenerative Medicine; Renal Artery; Renal Veins
PubMed: 29879472
DOI: 10.1016/j.semcdb.2018.06.001 -
Cells Nov 2022Lysosome-related organelles (LROs) are a group of functionally diverse, cell type-specific compartments. LROs include melanosomes, alpha and dense granules, lytic... (Review)
Review
Lysosome-related organelles (LROs) are a group of functionally diverse, cell type-specific compartments. LROs include melanosomes, alpha and dense granules, lytic granules, lamellar bodies and other compartments with distinct morphologies and functions allowing specialised and unique functions of their host cells. The formation, maturation and secretion of specific LROs are compromised in a number of hereditary rare multisystem disorders, including Hermansky-Pudlak syndromes, Griscelli syndrome and the Arthrogryposis, Renal dysfunction and Cholestasis syndrome. Each of these disorders impacts the function of several LROs, resulting in a variety of clinical features affecting systems such as immunity, neurophysiology and pigmentation. This has demonstrated the close relationship between LROs and led to the identification of conserved components required for LRO biogenesis and function. Here, we discuss aspects of this conserved machinery among LROs in relation to the heritable multisystem disorders they associate with, and present our current understanding of how dysfunctions in the proteins affected in the disease impact the formation, motility and ultimate secretion of LROs. Moreover, we have analysed the expression of the members of the CHEVI complex affected in Arthrogryposis, Renal dysfunction and Cholestasis syndrome, in different cell types, by collecting single cell RNA expression data from the human protein atlas. We propose a hypothesis describing how transcriptional regulation could constitute a mechanism that regulates the pleiotropic functions of proteins and their interacting partners in different LROs.
Topics: Humans; Arthrogryposis; Lysosomes; Melanosomes; Rare Diseases; Cholestasis; Kidney Diseases
PubMed: 36429129
DOI: 10.3390/cells11223702 -
Current Medicinal Chemistry 2023Solitary functioning kidney (SFK) is a subgroup of the Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT). Although the prognosis of these patients was... (Review)
Review
BACKGROUND
Solitary functioning kidney (SFK) is a subgroup of the Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT). Although the prognosis of these patients was considered good in the past, numerous studies have shown different levels of kidney damage associated with this condition. Serum creatinine measurement is still the most used marker to assess renal function, even though the limitations are widely known.
OBJECTIVE
The present review aims to summarize and update the scientific literature on congenital SFK, discussing its pathophysiology, diagnosis, complications, prognosis, role of novel urinary biomarkers, treatment, and follow-up.
RESULTS
The natural history of congenital SFK is still an unresolved issue due to several factors. Although it has not yet been proven in humans, Brenner's hyperfiltration hypothesis is the most concrete theory to explain the poor renal outcomes of patients born with one functioning kidney. The search for novel urinary biomarkers capable of assessing renal function and predicting renal outcomes has already started, but there are still few studies on this specific population. Among the most studied markers, Cystatin C, EGF and NGAL have shown potential usefulness for the follow-up of these patients. The treatment still relies on the search for kidney injury and general renoprotective measures.
CONCLUSION
Further research with a longer follow-up duration is needed to better understand the natural course of congenital SFK and the role of novel urinary biomarkers in this specific population. Thus, it will be possible to improve the prognosis of these patients.
Topics: Humans; Solitary Kidney; Glomerular Filtration Rate; Kidney; Kidney Diseases; Biomarkers
PubMed: 35770397
DOI: 10.2174/0929867329666220629142556 -
Life (Basel, Switzerland) May 2022Fibrosis is a severe complication of many acute and chronic kidney pathologies. According to current concepts, an imbalance in the synthesis and degradation of the... (Review)
Review
Fibrosis is a severe complication of many acute and chronic kidney pathologies. According to current concepts, an imbalance in the synthesis and degradation of the extracellular matrix by fibroblasts is considered the key cause of the induction and progression of fibrosis. Nevertheless, inflammation associated with the damage of tissue cells is among the factors promoting this pathological process. Most of the mechanisms accompanying fibrosis development are controlled by various hormones, which makes humoral regulation an attractive target for therapeutic intervention. In this vein, it is particularly interesting that the kidney is the source of many hormones, while other hormones regulate renal functions. The normal kidney physiology and pathogenesis of many kidney diseases are sex-dependent and thus modulated by sex hormones. Therefore, when choosing therapy, it is necessary to focus on the sex-associated characteristics of kidney functioning. In this review, we considered renal fibrosis from the point of view of vasoactive and reproductive hormone imbalance. The hormonal therapy possibilities for the treatment or prevention of kidney fibrosis are also discussed.
PubMed: 35629404
DOI: 10.3390/life12050737 -
American Journal of Physiology. Renal... Jun 2022Kidney organoids derived from human pluripotent stem cells constitute a novel model of disease, development, and regenerative therapy. Organoids are human,... (Review)
Review
Kidney organoids derived from human pluripotent stem cells constitute a novel model of disease, development, and regenerative therapy. Organoids are human, experimentally accessible, high throughput, and enable reconstitution of tissue-scale biology in a petri dish. Although gene expression patterns in organoid cells have been analyzed extensively, less is known about the functionality of these structures. Here, we review assays of physiological function in human kidney organoids, including best practices for quality control, and future applications. Tubular structures in organoids accumulate specific molecules through active transport, including dextran and organic anions, and swell with fluid in response to cAMP stimulation. When engrafted into animal models in vivo, organoids form vascularized glomerulus-like structures capable of size-selective filtration. Organoids exhibit metabolic, endocrine, injury, and infection phenotypes, although their specificity is not yet fully clear. To properly interpret organoid physiology assays, it is important to incorporate appropriate negative and positive controls, statistical methods, data presentation, molecular mechanisms, and clinical data sets. Improvements in organoid perfusion, patterning, and maturation are needed to enable branching morphogenesis, urine production, and renal replacement. Reconstituting renal physiology with kidney organoids is a new field with potential to provide fresh insights into classical phenomena.
Topics: Animals; Cell Differentiation; Humans; Kidney; Kidney Glomerulus; Morphogenesis; Organoids; Pluripotent Stem Cells
PubMed: 35379001
DOI: 10.1152/ajprenal.00400.2021 -
Biomaterials Advances Apr 2023Cancer nanomedicine has been investigated widely and boomed in the last two decades, resulting in designing nanostructures with biofunctionalization, giving rise to an... (Review)
Review
Cancer nanomedicine has been investigated widely and boomed in the last two decades, resulting in designing nanostructures with biofunctionalization, giving rise to an "All-in-One" multifunctional platform. The development of rational design technology with extended functionalities brought interdisciplinary researchers to work continuously, aiming to find a prevent or effectively treat the deadly disease of the century. Thus, it led to some Food and Drug Administration (FDA)-approving nano-based formulations for cancer treatment and opening a vast area of promising discoveries by exploiting different nanomaterials. Two-dimensional (2D) materials have recently gained tremendous interest among scientists because of their outstanding structural, optical, electronic, thermal, and mechanical characteristics. Among various 2D nanomaterials, MXenes are a widely studied nanosystem because of their close similarity to graphene analogs. So, it is synthesized using multiple approaches and exploits their inherited properties. But in most cases, surface functionalization techniques are carried out for targeting, site-specific drug clearance, renal clearance, and biocompatible with healthy cells. Thus, fabricating a multimodal agent for mono or combined therapies is also an image-guided diagnostic agent. This review will explain the recent and emerging advancements of MXenes-based composites as a multifunctional theragnostic agent and discuss the possibilities of transferring laboratory research to clinical translation.
Topics: United States; Humans; Medical Oncology; Nanostructures; Nanomedicine; Neoplasms
PubMed: 36842245
DOI: 10.1016/j.bioadv.2023.213354 -
American Journal of Physiology. Renal... Aug 2019The apolipoprotein L1 (APOL1) gene is unique to humans and gorillas and appeared ~33 million years ago. Since the majority of the mammals do not carry APOL1, it seems to... (Review)
Review
The apolipoprotein L1 (APOL1) gene is unique to humans and gorillas and appeared ~33 million years ago. Since the majority of the mammals do not carry APOL1, it seems to be dispensable for kidney function. APOL1 renal risk variants (RRVs; G1 and G2) are associated with the development as well as progression of chronic kidney diseases (CKDs) at higher rates in populations with African ancestry. Cellular expression of two APOL1 RRVs has been demonstrated to induce cytotoxicity, including necrosis, apoptosis, and pyroptosis, in several cell types including podocytes; mechanistically, these toxicities were attributed to lysosomal swelling, K depletion, mitochondrial dysfunction, autophagy blockade, protein kinase receptor activation, ubiquitin D degradation, and endoplasmic reticulum stress; notably, these effects were found to be dose dependent and occurred only in overtly APOL1 RRV-expressing cells. However, cellular protein expressions as well as circulating blood levels of APOL1 RRVs were not elevated in patients suffering from APOL1 RRV-associated CKDs. Therefore, the question arises as to whether it is gain or loss of function on the part of APOL1 RRVs contributing to kidney cell injury. The question seems to be more pertinent after the recognition of the role of APOL1 nonrisk (G0) in the transition of parietal epithelial cells and preservation of the podocyte molecular phenotype through modulation of the APOL1-miR-193a axis. With this background, the present review analyzed the available literature in terms of the known function of APOL1 nonrisk and how the loss of these functions could have contributed to two APOL1 RRV-associated CKDs.
Topics: Animals; Apolipoprotein L1; Humans; Kidney; Renal Insufficiency, Chronic
PubMed: 31241995
DOI: 10.1152/ajprenal.00233.2019 -
American Journal of Physiology. Renal... Mar 2021With no lysine kinase-4 (WNK4) belongs to a serine-threonine kinase family characterized by the atypical positioning of its catalytic lysine. Despite the fact that WNK4... (Review)
Review
With no lysine kinase-4 (WNK4) belongs to a serine-threonine kinase family characterized by the atypical positioning of its catalytic lysine. Despite the fact that WNK4 has been found in many tissues, the majority of its study has revolved around its function in the kidney, specifically as a positive regulator of the thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule of the nephron. This is explained by the description of gain-of-function mutations in the gene encoding WNK4 that causes familial hyperkalemic hypertension. This disease is mainly driven by increased downstream activation of the Ste20/SPS1-related proline-alanine-rich kinase/oxidative stress responsive kinase-1-NCC pathway, which increases salt reabsorption in the distal convoluted tubule and indirectly impairs renal K secretion. Here, we review the large volume of information that has accumulated about different aspects of WNK4 function. We first review the knowledge on WNK4 structure and enumerate the functional domains and motifs that have been characterized. Then, we discuss WNK4 physiological functions based on the information obtained from in vitro studies and from a diverse set of genetically modified mouse models with altered WNK4 function. We then review in vitro and in vivo evidence on the different levels of regulation of WNK4. Finally, we go through the evidence that has suggested how different physiological conditions act through WNK4 to modulate NCC activity.
Topics: Animals; Humans; Kidney Tubules, Distal; Nephrons; Potassium; Protein Serine-Threonine Kinases; Pseudohypoaldosteronism; Receptors, Drug; Sodium Chloride Symporters
PubMed: 33491560
DOI: 10.1152/ajprenal.00634.2020 -
Journal of Research in Medical Sciences... 2020In the treatment process of hypertriglyceridemia and diabetic nephropathy in type 2 diabetes, fenofibrate (FEN) is a well-known medication. FEN is from fibrate class... (Review)
Review
In the treatment process of hypertriglyceridemia and diabetic nephropathy in type 2 diabetes, fenofibrate (FEN) is a well-known medication. FEN is from fibrate class drugs that using orally; however, as a side effect, it is associated with serum creatinine level increasing. The aim of this review was to determine the real effect of FEN therapy on renal functions based on both experimental and clinical studies. For this review, using the keywords of "fenofibrate" and "renal" and "function," a variety of sources of information banks, including PubMed, Google Scholar, and Scopus, were used, and the published articles were considered and interpreted. Followed by searching in databases, 45 articles were collected. After screening these articles, based on the study source, they were devided into two parts: 23 articles on animal experiments and 22 articles clinical experiments. Based on this information, it seems that the protective mechanism of FEN is related to vascular endothelial functions. The increased creatinine by FEN is related to different sensitivities to FEN effects caused by a polymorphism in different patients. In patients with normal renal function, follow-up of serum creatinine would be necessary after FEN, but the discontinuation of FEN is not recommended. In addition, in diabetic patients with hypertriglyceridemia, FEN treatment would be suggested for protecting the kidney from diabetes-induced renal injury.
PubMed: 32582345
DOI: 10.4103/jrms.JRMS_772_19 -
World Journal of Diabetes Aug 2020Obesity and obesity-related co-morbidities, diabetes mellitus, and hypertension are among the fastest-growing risk factors of heart failure and kidney disease worldwide.... (Review)
Review
Obesity and obesity-related co-morbidities, diabetes mellitus, and hypertension are among the fastest-growing risk factors of heart failure and kidney disease worldwide. Obesity, which is not a unitary concept, or a static process, ranges from alterations in distribution to the amount of adiposity. Visceral adiposity, which includes intraabdominal visceral fat mass and ectopic fat deposition such as hepatic, cardiac, or renal, was robustly associated with a greater risk for cardiorenal morbidity than subcutaneous adiposity. In addition, morbid obesity has also demonstrated a negative effect on cardiac and renal functioning. The mechanisms by which adipose tissue is linked with the cardiorenal syndrome (CRS) are hemodynamic and mechanical changes, as well neurohumoral pathways such as insulin resistance, endothelial dysfunction, nitric oxide bioavailability, renin-angiotensin-aldosterone, oxidative stress, sympathetic nervous systems, natriuretic peptides, adipokines and inflammation. Adiposity and other associated co-morbidities induce adverse cardiac remodeling and interstitial fibrosis. Heart failure with preserved ejection fraction has been associated with obesity-related functional and structural abnormalities. Obesity might also impair kidney function through hyperfiltration, increased glomerular capillary wall tension, and podocyte dysfunction, which leads to tubulointerstitial fibrosis and loss of nephrons and, finally, chronic kidney disease. The development of new treatments with renal and cardiac effects in the context of type 2 diabetes, which improves mortality outcome, has highlighted the importance of CRS and its prevalence. Increased body fat triggers cellular, neuro-humoral and metabolic pathways, which create a phenotype of the CRS with specific cellular and biochemical biomarkers. Obesity has become a single cardiorenal umbrella or type of cardiorenal metabolic syndrome. This review article provides a clinical overview of the available data on the relationship between a range of adiposity and CRS, the support for obesity as a single cardiorenal umbrella, and the most relevant studies on the recent therapeutic approaches.
PubMed: 32864046
DOI: 10.4239/wjd.v11.i8.322