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Bulletin Du Cancer Mar 2012The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status,... (Review)
Review
The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body.
Topics: Acid-Base Equilibrium; Body Water; Calcium; Erythropoietin; Extracellular Fluid; Humans; Kidney; Kidney Glomerulus; Kidney Tubules; Phosphorus; Renal Circulation; Urine
PubMed: 22157516
DOI: 10.1684/bdc.2011.1482 -
Clinical Journal of the American... Aug 2014The glomerulus, the filtering unit of the kidney, is a unique bundle of capillaries lined by delicate fenestrated endothelia, a complex mesh of proteins that serve as... (Review)
Review
The glomerulus, the filtering unit of the kidney, is a unique bundle of capillaries lined by delicate fenestrated endothelia, a complex mesh of proteins that serve as the glomerular basement membrane and specialized visceral epithelial cells that form the slit diaphragms between interdigitating foot processes. Taken together, this arrangement allows continuous filtration of the plasma volume. The dynamic physical forces that determine the single nephron glomerular filtration are considered. In addition, new insights into the cellular and molecular components of the glomerular tuft and their contribution to glomerular disorders are explored.
Topics: Animals; Capillary Permeability; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney Diseases; Kidney Glomerulus; Models, Biological
PubMed: 24875196
DOI: 10.2215/CJN.09400913 -
Journal of Autoimmunity 2014Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of... (Review)
Review
Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease.
Topics: Anti-Glomerular Basement Membrane Disease; Early Diagnosis; Humans; Inflammation; Kidney Glomerulus; Vasculitis
PubMed: 24456936
DOI: 10.1016/j.jaut.2014.01.024 -
Cell Proliferation Mar 2020In recent years, although the development of clinical therapy for diabetic kidney disease (DKD) has made great progress, the progression of DKD still cannot be... (Review)
Review
In recent years, although the development of clinical therapy for diabetic kidney disease (DKD) has made great progress, the progression of DKD still cannot be controlled. Therefore, further study of the pathogenesis of DKD and improvements in DKD treatment are crucial for prognosis. Traditional studies have shown that podocyte injury plays an important role in this process. Recently, it has been found that glomerulotubular balance and tubuloglomerular feedback (TGF) may be involved in the progression of DKD. Glomerulotubular balance is the specific gravity absorption of the glomerular ultrafiltrate by the proximal tubules, which absorbs only 65% to 70% of the ultrafiltrate. This ensures that the urine volume will not change much regardless of whether the glomerular filtration rate (GFR) increases or decreases. TGF is one of the significant mechanisms of renal blood flow and self-regulation of GFR, but how they participate in the development of DKD in the pathological state and the specific mechanism is not clear. Injury to tubular epithelial cells (TECs) is the key link in DKD. Additionally, injury to glomerular endothelial cells (GECs) plays a key role in the early occurrence and development of DKD. However, TECs and GECs are close to each other in anatomical position and can crosstalk with each other, which may affect the development of DKD. Therefore, the purpose of this review was to summarize the current knowledge on the crosstalk between TECs and GECs in the pathogenesis of DKD and to highlight specific clinical and potential therapeutic strategies.
Topics: Animals; Diabetic Nephropathies; Disease Progression; Endothelium; Humans; Kidney Glomerulus; Kidney Tubules; Urothelium
PubMed: 31925859
DOI: 10.1111/cpr.12763 -
Experimental Cell Research May 2012MicroRNAs (miRNAs) are short non-coding RNAs regulating gene expression at the post-transcriptional level by blocking translation or promoting cleavage of their target... (Review)
Review
MicroRNAs (miRNAs) are short non-coding RNAs regulating gene expression at the post-transcriptional level by blocking translation or promoting cleavage of their target mRNAs. Increasing evidence shows that miRNAs play central roles in gene transcription, signal transduction and pathogenesis of human diseases. Diabetic nephropathy (DN) is a severe microvascular complication that can lead to end-stage renal disease. Increased expansion (hypertrophy) and accumulation of extracellular matrix (ECM) proteins such as collagen (fibrosis) in the glomerular mesangium along with glomerular podocyte dysfunction are major features of DN. Profiling of miRNAs and study\ of their functions in renal glomeruli can provide critical new information to advance our knowledge of DN as well as other kidney diseases and thereby uncover much needed new therapeutic targets. In this review, we summarize the biogenesis of miRNAs and their functions in the glomerulus, with particular emphasis on glomerular mesangial cells and podocytes related to the pathogenesis of DN.
Topics: Animals; Diabetic Nephropathies; Extracellular Matrix; Humans; Kidney Diseases; Kidney Glomerulus; Mesangial Cells; MicroRNAs; Podocytes
PubMed: 22421514
DOI: 10.1016/j.yexcr.2012.02.034 -
Cell and Tissue Research Aug 2021Proteases play a central role in regulating renal pathophysiology and are increasingly evaluated as actionable drug targets. Here, we review the role of proteolytic... (Review)
Review
Proteases play a central role in regulating renal pathophysiology and are increasingly evaluated as actionable drug targets. Here, we review the role of proteolytic systems in inflammatory kidney disease. Inflammatory kidney diseases are associated with broad dysregulations of extracellular and intracellular proteolysis. As an example of a proteolytic system, the complement system plays a significant role in glomerular inflammatory kidney disease and is currently under clinical investigation. Based on two glomerular kidney diseases, lupus nephritis, and membranous nephropathy, we portrait two proteolytic pathomechanisms and the role of the complement system. We discuss how profiling proteolytic activity in patient samples could be used to stratify patients for more targeted interventions in inflammatory kidney diseases. We also describe novel comprehensive, quantitative tools to investigate the entirety of proteolytic processes in a tissue sample. Emphasis is placed on mass spectrometric approaches that enable the comprehensive analysis of the complement system, as well as protease activities and regulation in general.
Topics: Animals; Humans; Inflammation; Kidney Glomerulus; Proteolysis
PubMed: 33864499
DOI: 10.1007/s00441-021-03433-8 -
Pediatric Nephrology (Berlin, Germany) Oct 2012A low nephron number is, according to Brenner's hyperfiltration hypothesis, associated with hypertension, glomerular damage and proteinuria, and starts a vicious cycle... (Review)
Review
A low nephron number is, according to Brenner's hyperfiltration hypothesis, associated with hypertension, glomerular damage and proteinuria, and starts a vicious cycle that ends in renal failure over the long term. Nephron endowment is set during foetal life, and there is no formation of nephrons after 34-36 weeks of gestation, indicating that many factors before that time-point may have an impact on kidney development and reduce nephron numbers. Such factors include maternal malnutrition, stress, diseases, such as diabetes, uteroplacental insufficiency, maternal and neonatal drugs and premature birth. However, other congenital anomalies, such as renal hypoplasia, unilateral renal agenesis or multicystic dysplastic kidney, may also lead to a reduced nephron endowment, with an increased risk for hypertension, renal dysfunction and the need for renal replacement therapy. This review focuses on the causes and consequences of a low nephron endowment and will illustrate why there is safety in glomerular numbers.
Topics: Animals; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Kidney Glomerulus; Organogenesis; Proteinuria; Risk Assessment; Risk Factors
PubMed: 22532329
DOI: 10.1007/s00467-012-2169-x -
Clinical Journal of the American... Jan 2018Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of... (Review)
Review
Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein-related kidney diseases.
Topics: Animals; Autoimmunity; B-Lymphocytes; Cell Lineage; Complement Activation; Cytotoxicity, Immunologic; Humans; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Paraproteinemias; Prognosis; Risk Factors
PubMed: 29114004
DOI: 10.2215/CJN.00560117 -
Journal of Pharmacological Sciences Sep 2016The number of people being diagnosed with end-stage renal disease is increasing globally. Therapeutic options to slow or halt the progression of kidney disease are... (Review)
Review
The number of people being diagnosed with end-stage renal disease is increasing globally. Therapeutic options to slow or halt the progression of kidney disease are limited and are not always successful, despite the increasing body of research and number of basic scientific reports in this field. Further studies are required to investigate new approaches to renal pathophysiology. State of the art optical imaging is a powerful tool used to non-invasively observe the pathophysiology of small animals and has the potential to elucidate the unknown mechanisms of renal disease and aid in our understanding of the disease. This paper is a brief summary of the current usefulness of intravital imaging using multiphoton microscopy and discusses possible future applications of the technique.
Topics: Acute Kidney Injury; Animals; Humans; Kidney Glomerulus; Microscopy, Fluorescence, Multiphoton
PubMed: 27581588
DOI: 10.1016/j.jphs.2016.08.001 -
Biomolecules May 2022Nitric oxide (NO) is a potent signaling molecule involved in many physiological and pathophysiological processes in the kidney. NO plays a complex role in glomerular... (Review)
Review
Nitric oxide (NO) is a potent signaling molecule involved in many physiological and pathophysiological processes in the kidney. NO plays a complex role in glomerular ultrafiltration, vasodilation, and inflammation. Changes in NO bioavailability in pathophysiological conditions such as hypertension or diabetes may lead to podocyte damage, proteinuria, and rapid development of chronic kidney disease (CKD). Despite the extensive data highlighting essential functions of NO in health and pathology, related signaling in glomerular cells, particularly podocytes, is understudied. Several reports indicate that NO bioavailability in glomerular cells is decreased during the development of renal pathology, while restoring NO level can be beneficial for glomerular function. At the same time, the compromised activity of nitric oxide synthase (NOS) may provoke the formation of peroxynitrite and has been linked to autoimmune diseases such as systemic lupus erythematosus. It is known that the changes in the distribution of NO sources due to shifts in NOS subunits expression or modifications of NADPH oxidases activity may be linked to or promote the development of pathology. However, there is a lack of information about the detailed mechanisms describing the production and release of NO in the glomerular cells. The interaction of NO and other reactive oxygen species in podocytes and how NO-calcium crosstalk regulates glomerular cells' function is still largely unknown. Here, we discuss recent reports describing signaling, synthesis, and known pathophysiological mechanisms mediated by the changes in NO homeostasis in the podocyte. The understanding and further investigation of these essential mechanisms in glomerular cells will facilitate the design of novel strategies to prevent or manage health conditions that cause glomerular and kidney damage.
Topics: Humans; Kidney; Kidney Glomerulus; Nitric Oxide; Nitric Oxide Synthase; Podocytes; Proteinuria
PubMed: 35740870
DOI: 10.3390/biom12060745