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Kidney International May 2018Sonography is increasingly being performed by clinicians and has applications throughout the spectrum of nephrology, including acute and chronic renal failure, urinary... (Review)
Review
Sonography is increasingly being performed by clinicians and has applications throughout the spectrum of nephrology, including acute and chronic renal failure, urinary obstruction, cystic disease, pain, hematuria, transplantation, kidney biopsy, temporary and permanent vascular access, and assessment of fluid status. The skill is relatively easily acquired, expedites patient care, and enhances the practice of nephrology. However, the lack of exposure in most training programs remains a major obstacle.
Topics: Clinical Competence; Education, Medical, Graduate; Humans; Kidney; Kidney Diseases; Nephrology; Point-of-Care Testing; Predictive Value of Tests; Reproducibility of Results; Ultrasonography
PubMed: 29477241
DOI: 10.1016/j.kint.2017.11.032 -
Journal of Cellular and Molecular... May 2023Chronic kidney diseases affect a substantial percentage of the adult population worldwide. This observation emphasizes the need for novel insights into the molecular...
Chronic kidney diseases affect a substantial percentage of the adult population worldwide. This observation emphasizes the need for novel insights into the molecular mechanisms that control the onset and progression of renal diseases. Recent advances in genomics have uncovered a previously unanticipated link between the non-coding genome and human kidney diseases. Here we screened and analysed long non-coding RNAs (lncRNAs) previously identified in mouse kidneys by genome-wide transcriptomic analysis, for conservation in humans and differential expression in renal tissue from healthy and diseased individuals. Our data suggest that LINC01187 is strongly down-regulated in human kidney tissues of patients with diabetic nephropathy and rapidly progressive glomerulonephritis, as well as in murine models of kidney diseases, including unilateral ureteral obstruction, nephrotoxic serum-induced glomerulonephritis and ischemia/reperfusion. Interestingly, LINC01187 overexpression in human kidney cells in vitro inhibits cell death indicating an anti-apoptotic function. Collectively, these data suggest a negative association of LINC01187 expression with renal diseases implying a potential protective role.
Topics: Animals; Humans; Mice; Diabetic Nephropathies; Down-Regulation; Glomerulonephritis; Kidney; RNA, Long Noncoding
PubMed: 37056054
DOI: 10.1111/jcmm.17014 -
Cell Stress & Chaperones Nov 2015Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous... (Review)
Review
Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.
Topics: Animals; Apoptosis; HSP70 Heat-Shock Proteins; Humans; Inflammation; Kidney Diseases; Nitric Oxide; Ureteral Obstruction
PubMed: 26228633
DOI: 10.1007/s12192-015-0622-z -
Kidney International May 2024Desmosomes are multi-protein cell-cell adhesion structures supporting cell stability and mechanical stress resilience of tissues, best described in skin and heart. The...
Desmosomes are multi-protein cell-cell adhesion structures supporting cell stability and mechanical stress resilience of tissues, best described in skin and heart. The kidney is exposed to various mechanical stimuli and stress, yet little is known about kidney desmosomes. In healthy kidneys, we found desmosomal proteins located at the apical-junctional complex in tubular epithelial cells. In four different animal models and patient biopsies with various kidney diseases, desmosomal components were significantly upregulated and partly miss-localized outside of the apical-junctional complexes along the whole lateral tubular epithelial cell membrane. The most upregulated component was desmoglein-2 (Dsg2). Mice with constitutive tubular epithelial cell-specific deletion of Dsg2 developed normally, and other desmosomal components were not altered in these mice. When challenged with different types of tubular epithelial cell injury (unilateral ureteral obstruction, ischemia-reperfusion, and 2,8-dihydroxyadenine crystal nephropathy), we found increased tubular epithelial cell apoptosis, proliferation, tubular atrophy, and inflammation compared to wild-type mice in all models and time points. In vitro, silencing DSG2 via siRNA weakened cell-cell adhesion in HK-2 cells and increased cell death. Thus, our data show a prominent upregulation of desmosomal components in tubular cells across species and diseases and suggest a protective role of Dsg2 against various injurious stimuli.
Topics: Animals; Humans; Mice; Cell Adhesion; Desmoglein 2; Desmosomes; Heart; Kidney Diseases
PubMed: 38395410
DOI: 10.1016/j.kint.2024.01.037 -
Kidney International Sep 1980
Review
Topics: Angiotensin II; Glomerular Filtration Rate; Humans; Hydrostatic Pressure; Kidney; Kidney Diseases; Nephrons; Phosphates; Potassium; Prostaglandins; Regional Blood Flow; Renin; Sodium; Ureteral Obstruction
PubMed: 7007707
DOI: 10.1038/ki.1980.138 -
American Journal of Physiology. Renal... Aug 2016Stress-induced activation of p38 MAPK and JNK signaling is a feature of both acute and chronic kidney disease and is associated with disease progression. Inhibitors of... (Review)
Review
Stress-induced activation of p38 MAPK and JNK signaling is a feature of both acute and chronic kidney disease and is associated with disease progression. Inhibitors of p38 MAPK or JNK activation provide protection against inflammation and fibrosis in animal models of kidney disease; however, clinical trials of p38 MAPK and JNK inhibitors in other diseases (rheumatoid arthritis and pulmonary fibrosis) have been disappointing. Apoptosis signal-regulating kinase 1 (ASK1) acts as an upstream regulator for the activation of p38 MAPK and JNK in kidney disease. Mice lacking the Ask1 gene are healthy with normal homeostatic functions and are protected from acute kidney injury induced by ischemia-reperfusion and from renal interstitial fibrosis induced by ureteric obstruction. Recent studies have shown that a selective ASK1 inhibitor substantially reduced renal p38 MAPK activation and halted the progression of nephropathy in diabetic mice, and this has led to a current clinical trial of an ASK1 inhibitor in patients with stage 3 or 4 diabetic kidney disease. This review explores the rationale for targeting ASK1 in kidney disease and the therapeutic potential of ASK1 inhibitors based on current experimental evidence.
Topics: Animals; Humans; Kidney Diseases; MAP Kinase Kinase 4; MAP Kinase Kinase Kinase 5; Mice; p38 Mitogen-Activated Protein Kinases
PubMed: 27226108
DOI: 10.1152/ajprenal.00208.2016 -
Pediatric Nephrology (Berlin, Germany) Apr 2014Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal... (Review)
Review
Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb (-/-) mice as well as the molecular pathways controlling disease progression in these animals.
Topics: Animals; Disease Models, Animal; Hydronephrosis; Mice
PubMed: 24276861
DOI: 10.1007/s00467-013-2658-6 -
Journal of the American Society of... Jun 2017Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent...
Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient's renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.
Topics: Anti-Bacterial Agents; Female; Humans; Kidney Diseases; Middle Aged; Uromodulin; Vancomycin
PubMed: 28082518
DOI: 10.1681/ASN.2016080867 -
BioMed Research International 2014The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects... (Review)
Review
The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects on glomerular filtration rate and tubule function, a chronic obstruction induces tubular and interstitial injury that results from the activation of different pathways. The progression of tubulointerstitial injury leads to chronic renal damage characterized by tubular atrophy, inflammatory cell infiltration, and interstitial fibrosis. Obstructive nephropathy is an evolving disease in which the renal damage continues even after relief of the obstruction. In particular, it has been demonstrated that the time of relief is the most important factor in predicting long-term renal function deterioration. In this setting, the EGF/MCP-1 ratio, urinary NGAL, and urinary KIM-1 are useful early biomarkers of progressive renal damage and could have a potential role in predicting the long-term renal outcome. This minireview summarizes the role of these emerging urinary biomarkers of obstructive nephropathy based on the current understanding of the pathophysiology of renal injury.
Topics: Acute Kidney Injury; Acute-Phase Proteins; Biomarkers; Chemokine CCL2; Epidermal Growth Factor; Glomerular Filtration Rate; Hepatitis A Virus Cellular Receptor 1; Humans; Kidney Diseases; Kidney Tubules; Lipocalin-2; Lipocalins; Membrane Glycoproteins; Proto-Oncogene Proteins; Receptors, Virus; Ureteral Obstruction
PubMed: 25101270
DOI: 10.1155/2014/303298 -
Kidney International Apr 2004
Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Kidney; Kidney Diseases; Male; Proteinuria; Ureteral Obstruction
PubMed: 15086496
DOI: 10.1111/j.1523-1755.2004.00533.x