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Comparative Biochemistry and... Apr 2021The renin-angiotensin system (RAS) evolved early among vertebrates and remains functioning throughout the vertebrate phylogeny and has adapted to various environments.... (Review)
Review
The renin-angiotensin system (RAS) evolved early among vertebrates and remains functioning throughout the vertebrate phylogeny and has adapted to various environments. The RAS is crucial for the regulation of blood pressure, fluid-electrolyte balance and tissue homeostasis. The RAS is also expressed during early ontogeny in renal and extra-renal tissues, and exerts unique vascular growth and differentiation functions. In this brief review, we describe advances from molecular-genetic and whole animal approaches and discuss similarities and unique aspects of the RAS in the context of embryonic development and vertebrates' phylogeny.
Topics: Animals; Arteries; Arterioles; Blood Pressure; Cell Differentiation; Chickens; Endothelium, Vascular; Homeostasis; Humans; Kidney; Phylogeny; RNA, Messenger; Renin; Renin-Angiotensin System; Water-Electrolyte Balance
PubMed: 33385525
DOI: 10.1016/j.cbpa.2020.110879 -
Medizinische Klinik, Intensivmedizin... Feb 2020Acute kidney injury (AKI) occurs in 30-50% of all intensive care patients. Renal replacement therapy (RRT) has to be initiated in 10-15%. The early in-hospital mortality... (Review)
Review
Acute kidney injury (AKI) occurs in 30-50% of all intensive care patients. Renal replacement therapy (RRT) has to be initiated in 10-15%. The early in-hospital mortality is about 50%. Up to 20% of all survivors develop chronic kidney disease after intensive care discharge and progress to end-stage kidney disease within the next 10 years. For timely initiation of prophylactic or therapeutic interventions, it is crucial to exactly determine the actual kidney function, i. e., glomerular filtration rate (GFR), and to gain insight into the further development of kidney function. Traditionally, renal function has been estimated using serum levels of creatinine or urea. Unfortunately, both are notoriously unreliable and insensitive in intensive care patients. Cystatin C has fewer non-GFR determinants when compared to creatinine and is more sensitive and accurate to detect early decreases of GFR. At present, new functional tests are discussed, namely the furosemide stress test (FST) and renal functional reserve (RFR). The FST consists of an intravenous infusion of 1.0-1.5 mg/kgBW furosemide to critically ill patients with AKI. An increase in urine output to >100 ml/h is indicative of a GFR >20 ml/min and almost certainly excludes progression to AKI stage III and need for RRT. Estimation of RFR can be made by short-term oral or intravenous administration of a high protein load. A subsequent increase in GFR defines the presence and the magnitude of functional reserve which can be activated. Loss of RFR is an indicator of loss of functioning nephron mass and incomplete recovery following AKI. Both FST and RFR can help to improve diagnosis and care of high-risk patients with acute and chronic kidney disease.
Topics: Acute Kidney Injury; Creatinine; Diuretics; Furosemide; Humans; Kidney; Kidney Function Tests; Renal Replacement Therapy
PubMed: 29327197
DOI: 10.1007/s00063-017-0400-z -
Journal of the Formosan Medical... Mar 2024Studies have highlighted the significant involvement of kidney pericytes in renal fibrosis. Kidney pericytes, classified as interstitial mesenchymal cells, are... (Review)
Review
Studies have highlighted the significant involvement of kidney pericytes in renal fibrosis. Kidney pericytes, classified as interstitial mesenchymal cells, are extensively branched, collagen-producing cells that closely interact with endothelial cells. This article aims to provide an overview of the recent advancements in understanding the physiological functions of pericytes and their roles in kidney diseases. In a healthy kidney, pericytes have essential physiological function in angiogenesis, erythropoietin (EPO) production, and the regulation of renal blood flow. Nevertheless, pericyte-myofibroblast transition has been identified as the primary cause of disease progression in acute kidney injury (AKI)-to-chronic kidney disease (CKD) continuum. Our recent research has demonstrated that hypoxia-inducible factor-2α (HIF-2α) regulates erythropoietin production in pericytes. However, this production is repressed by EPO gene hypermethylation and HIF-2α downregulation which were induced by transforming growth factor-β1-activated DNA methyltransferase and activin receptor-like kinase-5 signaling pathway during renal fibrosis, respectively. Additionally, AKI induces epigenetic modifications in pericytes, rendering them more prone to extracellular matrix production, cell migration and proliferation, thereby contributing to subsequent capillary rarefaction and renal fibrosis. Further investigation into the specific functions and roles of different subpopulations of pericytes may contribute for the development of targeted therapies aimed at attenuating kidney disease and mitigating their adverse effects.
Topics: Humans; Pericytes; Endothelial Cells; Kidney; Kidney Diseases; Renal Insufficiency, Chronic; Erythropoietin; Acute Kidney Injury; Fibrosis; Basic Helix-Loop-Helix Transcription Factors
PubMed: 37586973
DOI: 10.1016/j.jfma.2023.08.002 -
Nutrients Sep 2022Megalin is an endocytic receptor abundantly expressed in proximal tubular epithelial cells and other calciotropic extrarenal cells expressing vitamin D metabolizing... (Review)
Review
Megalin is an endocytic receptor abundantly expressed in proximal tubular epithelial cells and other calciotropic extrarenal cells expressing vitamin D metabolizing enzymes, such as bone and parathyroid cells. The receptor functions in the uptake of the vitamin D-binding protein (DBP) complexed to 25 hydroxyvitamin D (25(OH)D), facilitating the intracellular conversion of precursor 25(OH)D to the active 1,25 dihydroxyvitamin D3 (1,25(OH)D). The significance of renal megalin-mediated reabsorption of 25(OH)D and 1,25(OH)D has been well established experimentally, and other studies have demonstrated relevant roles of extrarenal megalin in regulating vitamin D homeostasis in mammary cells, fat, muscle, bone, and mesenchymal stem cells. Parathyroid gland megalin may regulate calcium signaling, suggesting intriguing possibilities for megalin-mediated cross-talk between calcium and vitamin D regulation in the parathyroid; however, parathyroid megalin functionality has not been assessed in the context of vitamin D. Within various models of chronic kidney disease (CKD), megalin expression appears to be downregulated; however, contradictory results have been observed between human and rodent models. This review aims to provide an overview of the current knowledge of megalin function in the context of vitamin D metabolism, with an emphasis on extrarenal megalin, an area that clearly requires further investigation.
Topics: Calcitriol; Calcium; Humans; Kidney; Kidney Diseases; Low Density Lipoprotein Receptor-Related Protein-2; Vitamin D; Vitamin D-Binding Protein
PubMed: 36145066
DOI: 10.3390/nu14183690 -
International Urology and Nephrology Apr 2022The objective of this study was to compare perioperative outcomes and total and split renal function between laparoscopic partial nephrectomy (LPN) and robot-assisted...
PURPOSE
The objective of this study was to compare perioperative outcomes and total and split renal function between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Predictive risk factors of preservation of operated renal function were also assessed.
METHODS
We retrospectively analyzed 173 patients who underwent LPN (n = 84) or RAPN (n = 89) between 2010 and 2020. After propensity score matching (1:1), perioperative outcomes and total and split renal function were assessed. Logistic regression analysis was used to evaluate predictive risk factors of preservation of operated renal function. Trifecta criteria were defined as negative surgical margins, warm ischemia time (WIT) < 25 min, and no complications more than Clavien-Dindo grade II within 4 weeks after surgery. Split renal function was evaluated by mercaptoacetyltriglycine renal scan.
RESULTS
After propensity score matching, 42 patients were allocated to each group. RAPN was associated with significantly shorter WIT (RAPN vs LPN: 12 vs 22 min; p < 0.0001) and higher trifecta achievement rate (93.3 vs 64.2%; p < 0.0001). Other perioperative outcomes and total and split renal function were not significantly different between LPN and RAPN. The R.E.N.A.L. nephrometry score (RNS) was a predictive risk factor of preservation of operated renal function in the multivariable logistic regression analysis (odds ratio 1.68, 95% confidence interval 1.29-2.20, p < 0.0001).
CONCLUSIONS
RAPN improved WIT and trifecta achievement rate, but it did not improve the preservation of operated renal function, for which RNS was found to be a strong predictive risk factor.
Topics: Humans; Kidney; Kidney Neoplasms; Laparoscopy; Nephrectomy; Propensity Score; Retrospective Studies; Robotic Surgical Procedures; Robotics; Treatment Outcome
PubMed: 35178639
DOI: 10.1007/s11255-022-03144-1 -
Current Topics in Developmental Biology 2023The nonmotile primary cilium is a sensory structure found on most mammalian cell types that integrates multiple signaling pathways involved in tissue development and...
The nonmotile primary cilium is a sensory structure found on most mammalian cell types that integrates multiple signaling pathways involved in tissue development and postnatal function. As such, mutations disrupting cilia activities cause a group of disorders referred to as ciliopathies. These disorders exhibit a wide spectrum of phenotypes impacting nearly every tissue. In the kidney, primary cilia dysfunction caused by mutations in polycystin 1 (Pkd1), polycystin 2 (Pkd2), or polycystic kidney and hepatic disease 1 (Pkhd1), result in polycystic kidney disease (PKD), a progressive disorder causing renal functional decline and end-stage renal disease. PKD affects nearly 1 in 1000 individuals and as there is no cure for PKD, patients frequently require dialysis or renal transplantation. Pkd1, Pkd2, and Pkhd1 encode membrane proteins that all localize in the cilium. Pkd1 and Pkd2 function as a nonselective cation channel complex while Pkhd1 protein function remains uncertain. Data indicate that the cilium may act as a mechanosensor to detect fluid movement through renal tubules. Other functions proposed for the cilium and PKD proteins in cyst development involve regulation of cell cycle and oriented division, regulation of renal inflammation and repair processes, maintenance of epithelial cell differentiation, and regulation of mitochondrial structure and metabolism. However, how loss of cilia or cilia function leads to cyst development remains elusive. Studies directed at understanding the roles of Pkd1, Pkd2, and Pkhd1 in the cilium and other locations within the cell will be important for developing therapeutic strategies to slow cyst progression.
Topics: Animals; Humans; Cilia; Kidney; Polycystic Kidney Diseases; Cysts; Mammals
PubMed: 38043952
DOI: 10.1016/bs.ctdb.2023.07.001 -
Advances in Physiology Education Sep 2023An Australia-wide consensus was reached on seven core concepts of physiology, one of which was "structure and function" with the descriptor "Structure and function are...
An Australia-wide consensus was reached on seven core concepts of physiology, one of which was "structure and function" with the descriptor "Structure and function are intrinsically related to all levels of the organism. In all physiological systems, the structure from a microscopic level to an organ level dictates its function." As a framework for the structure and function core concept, the renal system was unpacked by a team of 5 Australian Physiology educators from different universities with extensive teaching experience into hierarchical levels, with 5 themes and 25 subthemes up to 3 levels deep. Within , the structures that comprise the renal system were unpacked. Within , the physiological processes within the nephron such as filtration, reabsorption, and secretion were unpacked. Within , the processes involved in micturition were unpacked. In , the structures and processes involved in regulating renal blood flow and glomerular filtration were unpacked; and within , the role of the kidney in red blood cell production was unpacked. Twenty-one academics rated the difficulty and importance of each theme/subtheme, and results were analyzed using a one-way ANOVA. All identified themes were validated as "essential" to "important"/"moderately important" and rated between "difficult" to "not difficult." A similar framework consisting of structure, physiological processes, physical processes, and regulation can be used to unpack other body systems. Unpacking of the body systems will provide a list of what students should be taught in curricula across Australian universities and inform assessment and learning activities. This is the first attempt to unpack and validate the "structure and function" core concept in physiology with all Australian educators. We unpacked the renal system into themes with hierarchical levels, which were validated by an experienced team of Australian physiology educators. Our unpacking of the "structure and function" core concept provides a specific framework for educators to apply this important concept in physiology education.
Topics: Humans; Australia; Curriculum; Kidney; Learning; Physiology; Universities
PubMed: 37199738
DOI: 10.1152/advan.00150.2022 -
Transplantation Proceedings 2022Controversy surrounds the suitability of simultaneous liver-kidney transplant (SLKT) when compared with sequential transplant. Pretransplant renal failure is a...
UNLABELLED
Controversy surrounds the suitability of simultaneous liver-kidney transplant (SLKT) when compared with sequential transplant. Pretransplant renal failure is a post-transplant mortality predictor, and studies demonstrate worse functioning and lower survival of the renal graft when compared with kidney transplant alone (KTA).
BACKGROUND
This study compares renal function in patients with SLKT and those who received the contralateral kidney from the same donor.
MATERIAL AND METHODS
From June 2017 to February 2021, 5 SLKTs were performed in our hospital, and contralateral kidney grafts took place in other Andalusian Modification on Diet in Renal Disease-4 hospitals. Renal function was assessed according to glomerular filtration (GF) by the formula (that uses 4 variables: creatinine, age, sex, and race) during different periods of time; and the average increase of GF during 6 months in both groups was compared. Other factors from donors and receptors were also compared.
RESULTS
No statistically significant differences between average GF in both groups were found; however, there were statistically significant differences when we compared the GF increase 6 months after the transplant in both groups of patients, being that increase higher in patients with KTA.
CONCLUSIONS
Despite our small sample size, our study found that patients with SLKT have worse functioning of the kidney graft than those with KTA.
Topics: Graft Survival; Humans; Infant; Kidney; Kidney Transplantation; Liver; Retrospective Studies; Treatment Outcome
PubMed: 34920882
DOI: 10.1016/j.transproceed.2021.08.059 -
Frontiers in Immunology 2020Current organ transplantation therapy is life-saving but accompanied by well-recognized side effects due to post-transplantation systematic immunosuppressive treatment.... (Review)
Review
Current organ transplantation therapy is life-saving but accompanied by well-recognized side effects due to post-transplantation systematic immunosuppressive treatment. Dendritic cells (DCs) are central instigators and regulators of transplantation immunity and are responsible for balancing allograft rejection and tolerance. They are derived from monocyte-macrophage DC progenitors originating in the bone marrow and are classified into different subsets based on their developmental, phenotypical, and functional criteria. Functionally, DCs instigate allograft immunity by presenting donor antigens to alloreactive T cells via direct, indirect, and semidirect recognition pathways and provide essential signaling for alloreactive T cell activation via costimulatory molecules and pro-inflammatory cytokines. Regulatory DCs (DCregs) are characterized by a relatively low expression of major histocompatibility complex, costimulatory molecules, and altered cytokine production and exert their regulatory function through T cell anergy, T cell deletion, and regulatory T cell induction. In rodent transplantation studies, DCreg-based therapy, by targeting or infusion of generated DCregs, exhibits promising potential as a natural, well-tolerated, organ-specific therapeutic strategy for promoting lasting organ-specific transplantation tolerance. Recent early-phase studies of DCregs have begun to examine the safety and efficacy of DCreg-induced allograft tolerance in living-donor renal or liver transplantations. The present review summarizes the basic characteristics, function, and translation of DCregs in transplantation tolerance induction.
Topics: Allografts; Animals; Cell Differentiation; Dendritic Cells; Graft Rejection; Graft Survival; Humans; Immunomodulation; Lymphocyte Activation; Organ Transplantation; T-Lymphocytes; Transplantation Tolerance
PubMed: 33162996
DOI: 10.3389/fimmu.2020.582658 -
Nutrients Jul 2021Clinical characteristics of nutrition status in acute myocardial infarction (AMI) patients with cancer remains unknown. Therefore, this study aimed to clarify the...
Clinical characteristics of nutrition status in acute myocardial infarction (AMI) patients with cancer remains unknown. Therefore, this study aimed to clarify the differences of clinical parameters, including nutrition status, between AMI patients with and without history of cancer. This retrospective cohort study, using the database of AMI between 2014 and 2019 in Kurume University Hospital, enrolled 411 patients; AMI patients without cancer ( = 358, 87.1%) and with cancer ( = 53, 12.9%). AMI patients with cancer were significantly older with lower body weight, worse renal function, and worse nutrition status. Next, we divided the patients into 4 groups by cancer, age, and plaque area, detected by coronary image devices. The prediction model indicated that nutrition, lipid, and renal functions were significant predictors of AMI with cancer. The ordinal logistic regression model revealed that worse nutrition status, renal dysfunction, lower uric acid, and elevated blood pressure were significant predictors. Finally, we were able to calculate the probability of the presence of cancer, by combining each factor and scoring. Worse nutrition status and renal dysfunction were associated with AMI with cancer, in which nutrition status was a major different characteristic from those without cancer.
Topics: Aged; Female; Humans; Kidney; Logistic Models; Male; Middle Aged; Myocardial Infarction; Neoplasms; Nutritional Status; Retrospective Studies; Uric Acid
PubMed: 34444823
DOI: 10.3390/nu13082663