-
Internal Medicine (Tokyo, Japan) May 2000Obstructive nephropathy is a relatively common entity that is treatable and often reversible. It occurs at all ages from infancy to elderly subjects. Obstructive... (Review)
Review
Obstructive nephropathy is a relatively common entity that is treatable and often reversible. It occurs at all ages from infancy to elderly subjects. Obstructive uropathy is classified according to the degree, duration and site of the obstruction. It is the result of functional or anatomic lesions located in the urinary tract. The causes of obstructive uropathy are many. Obstruction of the urinary tract may decrease renal blood flow and the glomerular filtration rate. Several abnormalities in tubular function may occur in obstructive nephropathy. These include decreased reabsorption of solutes and water, inability to concentrate the urine and impaired excretion of hydrogen and potassium. Renal interstitial fibrosis is a common finding in patients with long-term obstructive uropathy. Several factors: macrophages, growth factors, hypoxia, cytokines are involved in the pathogenesis of interstitial fibrosis. It has been shown that ACE inhibitors ameliorate the interstitial fibrosis in animals with obstructive uropathy.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Humans; Hydronephrosis; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; NF-kappa B; Nephritis, Interstitial; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renal Circulation; Tumor Necrosis Factor-alpha
PubMed: 10830173
DOI: 10.2169/internalmedicine.39.355 -
Kidney International Jun 2009Renal fibrosis is the hallmark of progressive renal disease of virtually any etiology. The model of unilateral ureteral obstruction (UUO) in the rodent generates... (Review)
Review
Renal fibrosis is the hallmark of progressive renal disease of virtually any etiology. The model of unilateral ureteral obstruction (UUO) in the rodent generates progressive renal fibrosis. Surgically created UUO can be experimentally manipulated with respect to timing, severity, and duration, while reversal of the obstruction permits the study of recovery. The use of genetically engineered mice has greatly expanded the utility of the model in studying molecular mechanisms underlying the renal response to UUO. Ureteral obstruction results in marked renal hemodynamic and metabolic changes, followed by tubular injury and cell death by apoptosis or necrosis, with interstitial macrophage infiltration. Proliferation of interstitial fibroblasts with myofibroblast transformation leads to excess deposition of the extracellular matrix and renal fibrosis. Phenotypic transition of resident renal tubular cells, endothelial cells, and pericytes has also been implicated in this process. Technical aspects of the UUO model are discussed in this review, including the importance of rodent species or strain, the age of the animal, surgical procedures, and histological methods. The UUO model is likely to reveal useful biomarkers of progression of renal disease, as well as new therapies, which are desperately needed to allow intervention before the establishment of irreversible renal injury.
Topics: Animals; Disease Models, Animal; Fibrosis; Kidney Diseases; Mice; Ureteral Obstruction
PubMed: 19340094
DOI: 10.1038/ki.2009.86 -
Seminars in Nephrology Mar 1988
Review
Topics: Animals; Chronic Disease; Humans; Hydronephrosis; Kidney Diseases; Nephritis, Interstitial; Ureteral Obstruction; Vesico-Ureteral Reflux
PubMed: 3283892
DOI: No ID Found -
American Journal of Physiology. Renal... Nov 2002Interstitial fibrosis has a major role in the progression of renal diseases. Several animal models are available for the study of renal fibrosis. The models of... (Review)
Review
Interstitial fibrosis has a major role in the progression of renal diseases. Several animal models are available for the study of renal fibrosis. The models of aminonucleoside-induced nephrotic syndrome, cyclosporin nephrotoxicity, and passive Heyman nephritis are characterized by molecular and cellular events similar to those that occur in obstructive nephropathy. Additionally, inhibition of angiotensin-converting enzyme exerts salutary effects on the progression of renal fibrosis in obstructive nephropathy. Unilateral ureteral obstruction (UUO) has emerged as an important model for the study of the mechanisms of renal fibrosis and also for the evaluation of the impact of potential therapeutic approaches to ameliorate renal disease. Many quantifiable pathophysiological events occur over the span of 1 wk of UUO, making this an attractive model for study. This paper reviews some of the ongoing studies that utilized a rodent model of UUO. Some of the findings of the animal model have been compared with observations made in patients with obstructive nephropathy. Most of the evidence suggests that the rodent model of UUO is reflective of human renal disease processes.
Topics: Animals; Fibrosis; Humans; Kidney Diseases; Ureteral Obstruction
PubMed: 12372761
DOI: 10.1152/ajprenal.00362.2001 -
Kidney International Feb 2003
Review
Topics: Animals; Animals, Newborn; Disease Models, Animal; Kidney Diseases; Ureteral Obstruction
PubMed: 12631145
DOI: 10.1046/j.1523-1755.2003.00790.x -
Nephron Jan 2000Obstructive nephropathy is one of the most important causes of renal failure in infants and children, while polycystic kidney disease (PKD) is a major cause of renal... (Review)
Review
Obstructive nephropathy is one of the most important causes of renal failure in infants and children, while polycystic kidney disease (PKD) is a major cause of renal failure in the adult population. This review summarizes the evidence that there may be a number of mechanisms common to the pathophysiology of both conditions. In animal models of obstructive nephropathy and PKD, the renal tubular expression of epidermal growth factor is suppressed, and expression of clusterin is increased, both of which suggest arrested maturation or dedifferentiation of the tubular cell. There is a marked increase in apoptosis of epithelial cells in dilated tubules, associated with an increase in apoptotic stimuli. The renin-angiotensin system is activated in both obstructive nephropathy and PKD, which may contribute to tubular atrophy and interstitial fibrosis, which characterize the progression of both conditions. Focal cystic dilatation of the tubule is found in obstructive nephropathy, while tubular obstruction is present in cystic kidney disease. It is therefore likely that elucidation of the effects of mechanical stretch on renal tubular epithelial cells will contribute to our understanding of both conditions.
Topics: Adult; Animals; Apoptosis; Child, Preschool; Epidermal Growth Factor; Humans; Infant; Kidney Diseases; Kidney Tubules; Polycystic Kidney Diseases; Renin-Angiotensin System; Ureteral Obstruction
PubMed: 10644902
DOI: 10.1159/000045532 -
Proceedings of the Royal Society of... Dec 1970
Topics: Animals; Humans; Kidney Diseases; Swine; Urography; Urologic Diseases
PubMed: 5490774
DOI: No ID Found -
Scientific Reports Dec 2019Urinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed...
Urinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation. Here, we studied necroptosis and necroinflammation in obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in neonatal C57Bl/6J mice. Ureteral obstruction induced tubular dilatation, tubular basement membrane thickening, cast formation, and increased expression of kidney injury molecule-1 (KIM-1). Morphological investigations showed either apoptotic or necrotic cells in the tubular compartment. Biochemical analysis revealed increased caspase-8 activity and upregulation of RIPK3 as well as phosphorylated-MLKL in UUO-kidneys. Pro-inflammatory cytokines (IL-1α, INF-γ, TNF-α) were upregulated following UUO. Taken together we show that necroptosis and necroinflammation are accompanied phenomena in neonatal kidneys with obstruction. These findings may help to develop novel strategies to treat congenital obstructive nephropathy.
Topics: Animals; Animals, Newborn; Apoptosis; Cytokines; Inflammation; Kidney; Kidney Diseases; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Necroptosis; Phosphorylation; Protein Kinases; Receptor-Interacting Protein Serine-Threonine Kinases
PubMed: 31819111
DOI: 10.1038/s41598-019-55079-w -
The Journal of Small Animal Practice Jun 2018Feline ureteral obstructions are an increasingly recognised and challenging diagnostic and management problem. Many cats with ureteral obstructions are critically ill at... (Review)
Review
Feline ureteral obstructions are an increasingly recognised and challenging diagnostic and management problem. Many cats with ureteral obstructions are critically ill at the time of diagnosis, especially if there is dysfunction of the contralateral kidney. They may present with varying severities of acute kidney injury, electrolyte disturbances, and may have comorbidities such as heart disease that complicate perioperative and long-term management. Medical management, which may consist of rehydration and restoration of intravascular volume with intravenous fluid therapy, osmotic diuresis, ureteral muscle relaxation, and antimicrobials for infection, is important in feline ureteral obstruction patients. Despite medical management, many cats with ureteral obstructions will require decompression of the obstructed kidney to relieve pressure-nephropathy and restore urine flow. However, some cats may be too unstable for traditional medical management and require more emergent intervention to relieve the obstruction and address the life-threatening sequelae to acute kidney injury, such as hyperkalaemia and fluid overload. Both surgical and interventional methods to address ureteral obstructions have been described in veterinary medicine, though debate continues as to the ideal approach.
Topics: Acute Kidney Injury; Animals; Cat Diseases; Cats; Fluid Therapy; Ureteral Obstruction; Urinary Calculi
PubMed: 29767451
DOI: 10.1111/jsap.12844 -
Toxicologic Pathology Feb 2019The chemically induced accumulation of α2u-globulin protein in male rats causes specific renal lesions and subsequent nephropathy. Herein, we report additional parallel...
The chemically induced accumulation of α2u-globulin protein in male rats causes specific renal lesions and subsequent nephropathy. Herein, we report additional parallel findings in the kidney of male rats consistent with obstructive and retrograde nephropathy. Kidney and urinary bladder samples were evaluated from Wistar rats treated with RG7129 for 2 week and 8 week and from an 8-week mechanistic study using females, intact and castrated males. Histopathological findings were present in intact males in all studies, including hyaline droplet accumulation and granular casts consistent with α2u-globulin nephropathy. In addition, tubular degeneration and regeneration, tubular changes extending from papilla to cortex, tubular dilation, and interstitial and luminal inflammation were observed consistent with retrograde and obstructive nephropathy. Renal and urinary lesions and their severity increased in a time- and dose-dependent manner. Urinalysis findings, including increases in leukocytes, protein, and in kidney biomarkers, kidney injury molecule 1 and clusterin, were present only in intact males. No treatment-related changes were observed in female rats or in castrated males. These results indicate that RG7129 induces α2u-globulin nephropathy, associated with retrograde and obstructive nephropathy secondary to precipitation in intact male rats only, constituting a species- and sex-specific syndrome that is not expected to occur in humans or other species.
Topics: Alpha-Globulins; Animals; Enzyme Inhibitors; Female; Kidney Diseases; Male; Neuroprotective Agents; Rats; Rats, Wistar
PubMed: 30587097
DOI: 10.1177/0192623318816039