Materiały źródłowe

• #1 Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11229834/

  Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary tract. […] Acute obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the kidney. […] A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management. […] Acute UTO results in a disruption of urine flow, causing an elevation in pressure within the urinary tract. […] Pressure increase is transmitted retrogradely, ultimately impacting renal intratubular flow and inflicting injury on the kidney leading to changes in the kidneys and urinary tract. […] An initial compensatory hemodynamic response produces functional changes in the kidney, which, in the absence of obstruction relief, may structurally affect the kidneys resulting in permanent damage.

• #2 Ureteral obstruction – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/ureteral-obstruction/symptoms-causes/syc-20354676

  A ureteral obstruction is a blockage in one or both of the tubes (ureters) that carry urine from the kidneys to the bladder. Ureteral obstruction can be cured. However, if it’s not treated, symptoms can quickly move from mild pain, fever and infection to severe loss of kidney function, sepsis and death. […] Different types of ureteral obstruction have different causes, some of them present at birth (congenital). […] A blockage (obstruction) where the ureter connects to the kidney or bladder. This prevents urine flow. A blockage where the ureter and kidney meet (ureteropelvic junction) may cause the kidney to swell and eventually stop working. This condition can be congenital or can develop with typical childhood growth, result from an injury or scarring, or in rare cases, develop from a tumor. A blockage where the ureter and bladder meet (ureterovesical junction) may cause urine to back up into the kidneys.

• #2 Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11229834/

  The establishment of renal injury starts with the retrograde transmission of the elevation of urinary tract pressure, which produces dilation of the urinary tract and consequently hydronephrosis. […] High intratubular pressure produces an interstitial expansion of the kidney extracellular matrix which triggers an inflammatory cascade with cellular infiltrates and interstitial fibrosis, finally producing tubular cell apoptosis. […] The persistence of unrelieved obstruction results in tubulointerstitial necrosis with possible associated glomerulosclerosis. […] The effects of UTO on the kidney mainly affect three aspects of tubular function; sodium transport, urinary concentrating ability and urinary acidification. […] These changes are more pronounced in cases of BUO than in UUO. […] The timing and degree of obstruction leads to differences in physiopathological pathways and consequently the clinical implications derived from the initial insult.

• #3 Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

  https://www.wjgnet.com/2220-6124/full/v13/i2/93322.htm

  Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary tract. […] Acute obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the kidney. […] A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management. […] Understanding the different mechanisms underlying obstructive renal failure is of vital importance, as it guides diagnostic strategies and therapeutic interventions required. […] The establishment of renal injury starts with the retrograde transmission of the elevation of urinary tract pressure, which produces dilation of the urinary tract and consequently hydronephrosis.

• #3 Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

  https://www.wjgnet.com/2220-6124/full/v13/i2/93322.htm

  High intratubular pressure produces an interstitial expansion of the kidney extracellular matrix which triggers an inflammatory cascade with cellular infiltrates and interstitial fibrosis, finally producing tubular cell apoptosis. […] The persistence of unrelieved obstruction results in tubulointerstitial necrosis with possible associated glomerulosclerosis. […] The timing and degree of obstruction leads to differences in physiopathological pathways and consequently the clinical implications derived from the initial insult. […] Therefore, our aim was to compile and summarize the existing evidence on obstructive uropathy into a single article, spanning from its etiology to potential sequelae. […] Management of UTO does not end after urinary diversion, there are several side effects and complications derived from the intervention that need to be early identified and corrected.

• #4 Urinary Tract Obstruction: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/778456-overview

  Chronic urinary tract obstruction can lead to permanent damage to the urinary tract. […] Progressive back pressure on the ureters and kidneys can occur and can cause hydroureter and hydronephrosis. The ureter can then become dilated and tortuous, with the inability to adequately propel urine forward. Hydronephrosis can cause permanent nephron damage and renal failure. Urinary stasis along any portion of the urinary tract increases the risk of stone formation and infection, and, ultimately, upper urinary tract injury. Urinary tract obstruction can have long-lasting effects on the physiology of the kidney, including its ability to concentrate urine. […] In the setting of an acute urinary tract obstruction, an increase in intraluminal pressure causes smooth muscle cells to increase contractions and ureteral wall pressure. As the duration of the obstruction lengthens, smooth muscle cells contract with less force and ureteral wall dilation increases. With a superimposed urinary infection, as often occurs in chronic obstruction, the loss of muscle tone is even more dramatic and progressive dilation occurs with no further increase or decrease in wall tension.

• #5 Pathophysiology of Urinary Tract Obstruction | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-urinary-tract-obstruction/

  Animal experiments have demonstrated a triphasic pattern of RBF and ureteral pressure changes in UUO that differs from BUO or unilateral obstruction of a solitary kidney. […] Thus it is likely that both PGE2 and NO contribute to the net renal vasodilation that occurs early following UUO. […] Thus reduced whole kidney GFR at this stage of obstruction is due not only to reduced perfusion of individual glomeruli, related to afferent vasoconstriction and reduced PGC, but also to global reduction in filtration related to no perfusion or underperfusion of many glomeruli. […] Infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril attenuates the declines in RBF and GFR in UUO, suggesting that angiotensin II is an important mediator of the preglomerular vasoconstriction occurring during the second and third phases of UUO.

• #6 Urinary obstruction pathophysiology | PPT

  https://www.slideshare.net/slideshow/urinary-obstruction-pathophysiology/249372644

  Urinary tract obstruction can result in permanent renal damage. The degree of injury depends on: Severity of the obstruction. (Partial or complete, unilateral or bilateral), Chronicity of the obstruction (acute vs chronic), Baseline condition of the kidneys and Other mitigating factors such as UTI. […] Unilateral Urinary Obstruction More commonly encountered. Triphasic changes in RBF and ureteral pressure changes have been noted. Phase 1 one to two hours Phase 2 Three to four hours Phase 3- Late phase […] Unilateral Urinary Obstruction Decrease GFR Increase RBF Increase Filtration pressure More urine in Ureter Increased Ureteric Pressure UUO […] Late Phase NO production declines with depletion of L-arginine substrate or Decreased NOS activity or Vascular endothelium becomes less responsive to the action of NO following UO.

• #7

  https://link.springer.com/article/10.1007/BF00870378

  Following ureteral obstruction there is a progressive fall in glomerular filtration rate (GFR) due to a reduction in single nephron glomerular filtration rate (SNGFR) and a reduced number of filtering nephrons. […] The vasoactive hormones thromboxane A2 and angiotensin II are implicated in the pathogenesis of the vasoconstriction following ureteral obstruction and they also reduce the glomerular ultrafiltration coefficient by causing mesangial contraction. […] The pathophysiology of these alterations in renal function is discussed.

• #8 Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction

  https://www.krcp-ksn.org/journal/view.php?number=6313&viewtype=pubreader

  Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. […] The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. […] Blockage of urine flow caused by UUO increases the hydrostatic pressure and impacts feedback to the distal and proximal tubules, which leads to mechanical stretching that damages the tubular cells and decreases the GFR. Both short-term UUO (as early as 6 hours) and prolonged UUO (5 weeks) activate the components of the renin-angiotensin system (RAS), such as expression of renin messenger RNA, ACE activity, and Ang II content, which contribute to renal fibrosis.

• #9 Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction

  https://www.krcp-ksn.org/journal/view.php?number=6313&viewtype=pubreader

  Oxidative stress plays a pivotal role in a wide array of kidney diseases through the overproduction of ROS. […] Interstitial inflammation precedes ongoing fibrosis and is the predominant feature of renal fibrosis in UUO. […] Myofibroblasts belong to a heterogeneous superfamily derived from a variety of origins, including the epithelium through epithelial-to-mesenchymal transition, endothelia through endothelial-to-mesenchymal transition, local fibroblast or pericyte proliferation, and the macrophage-to-myofibroblast transition. […] Apoptosis (type I programmed cell death) is an active mechanism of cell clearance and plays an essential role in cell number regulation during development and organ homeostasis, and following insults. […] Autophagy (type II programmed cell death) is an evolutionarily conserved, lysosome-mediated cellular process of degradation of damaged organelles, protein aggregates, and other macromolecules in the cytoplasm, and is involved in the regulation of cell death and proliferation.

• #10 Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11229834/

  A proinflammatory immune cellular response is triggered which results in interstitial expansion and fibrosis which may lead to tubulointerstitial necrosis. […] This fibrotic response leads to the deposition of elastin, collagen and other pro-fibrotic molecules which may lead to irreparable tissue damage in early phases of obstruction.

• #11 Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction

  https://www.krcp-ksn.org/journal/view.php?number=6313&viewtype=pubreader

  Sustained ER stress is cytotoxic to renal cells and mitochondrial damage and ER stress are involved in the development of renal fibrosis in the UUO model. […] The pathogenesis of renal fibrosis is complex and multifactorial, and is orchestrated by activation of renin-angiotensin system, oxidative stress, inflammation, TGF-1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway.

• #12 Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction – Mercer University

  https://catalog.mercer.edu/discovery/fulldisplay?docid=cdi_kiss_primary_4122588&context=PC&vid=01GALI_MUM:MainLibrary&lang=en&adaptor=Primo%20Central&tab=MAINBLENDED&query=sub%2Cexact%2C%20Endoplasmic%20reticulum%20%2CAND&mode=advanced&offset=20

  Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway.

• #13 Matrix Metalloproteinases in Ureteropelvic Junction Obstruction: Their Role in Pathogenesis and Their Use as Clinical Markers

  https://www.mdpi.com/2073-4409/14/7/520

  The obstruction of the urinary tract is responsible for obstructive nephropathy (ON), also known as uropathy, which may then evolve in a renal parenchymal disease (hydronephrosis). […] Despite the known changes in the local tissue microenvironment at the site of the urinary tract obstruction, the role of MMPs in ureteropelvic junction obstruction (UPJO) and, therefore, in the pathogenesis of renal damage in ON is not well-documented. […] The possible roles of MMPs in UPJO and, therefore, in the pathogenesis of renal damage in obstructive nephropathy are not widely documented in the literature. […] It has been observed that MMPs can stimulate renal fibrosis even during the evolution of post-obstructive renal damage by favoring an epithelial–mesenchymal transition (EMT). […] The current view of UPJO as the cause of neonatal hydronephrosis points to a multifactorial and polygenic etiology of obstructive damage.

• #14 Matrix Metalloproteinases in Ureteropelvic Junction Obstruction: Their Role in Pathogenesis and Their Use as Clinical Markers

  https://www.mdpi.com/2073-4409/14/7/520

  Once UPJO is established, during the early development of the renal tract, disease progression leads to tubulointerstitial inflammation and fibrosis, both of which affect the growth of the obstructed kidney, resulting in the compensatory expansion of the contralateral kidney. […] The succession of the renal response to urinary tract obstruction and tubular expansion involves a chain of events resulting in impaired regulation of intrarenal components of the renin–angiotensin system (RAS), changes in inflammatory processes, etc. […] The obstruction of the urinary tract is responsible for obstructive nephropathy (ON), also known as uropathy, which may then evolve in a renal parenchymal disease (hydronephrosis). […] The causes of this disease can be multiple: structural constriction of the ureteral lumen, impaired ureteral smooth muscle development affecting peristalsis, as well as secondary ureteral injury with renal failure.

• #15 Pathophysiology of Urinary Tract Obstruction | Abdominal Key

  https://abdominalkey.com/pathophysiology-of-urinary-tract-obstruction/

  The kidneys response to the release of UUO depends on the duration and extent of obstruction and is also species specific. […] In summary, both UUO and BUO involve increases in renal vascular resistances and increases in ureteral pressures. However, the timing and regulation of these changes differ. With UUO, early renal vasodilation primarily mediated by prostaglandins and NO is followed by prolonged vasoconstriction and normalization of intratubular-ureteral pressure as the contralateral kidney contributes to fluid balance. With BUO, little early vasodilation is seen, and vasoconstriction is more profound. […] Thus dysregulation of aquaporin water channels in the proximal tubule, thin descending loop, and collecting duct may contribute to the long-term polyuria and impaired concentrating capacity caused by obstructive nephropathy. Increases in angiotensin II may be a mediator of these changes.

• #16 Urinary obstruction pathophysiology | PPT

  https://www.slideshare.net/slideshow/urinary-obstruction-pathophysiology/249372644

  Bilateral Ureteric Obstruction Afferent Dilataion, Efferent Constriction ANP […] Partial Ureteral Obstruction Proper animal models not available. Behaves mostly like UUO. Generally there is decreased RBF and GFR. Shift in blood flow from outer cortex to inner cortex is noted. […] Obstruction causes urinary acidification. Associated with decreased H+ secretion and defective HCO3- absorption. Multiple acid-base transporters are downregulated. Mediated by iNOS. […] Duration and severity of obstruction has significant influence. Longer periods are associated with diminished GFR return. It is due to persistent vasoconstriction of afferent arteriole.

• #17 Obstructive Uropathy – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/obstructive-uropathy/obstructive-uropathy

  Pathologic findings consist of dilation of the collecting ducts and distal tubules and chronic tubular atrophy with little glomerular damage. Dilation takes 3 days from the onset of obstructive uropathy to develop; before then, the collecting system is relatively noncompliant and less likely to dilate. Obstructive uropathy without dilation can also occur when fibrosis or a retroperitoneal tumor encases the collecting systems, when obstructive uropathy is mild and renal function is not impaired, and in the presence of an intrarenal pelvis. […] Obstructive nephropathy is renal dysfunction (renal insufficiency, renal failure, or tubulointerstitial damage) resulting from urinary tract obstruction. The mechanism involves, among many factors, increased intratubular pressure, local ischemia, and, often, urinary tract infection (UTI). If obstruction is bilateral, nephropathy may result in renal insufficiency. Renal insufficiency may rarely occur when obstruction is unilateral because autonomic-mediated vascular or ureteral spasm may affect the functioning kidney. […] The time and rate at which irreversible damage to the kidney (or kidneys) develops after obstruction depends on so many factors that it is hard to predict. To prevent irreversible damage, obstruction of the urinary tract should be diagnosed and treated as promptly as possible.

• #18 The pathophysiology of ureteral obstruction – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8518834/

  Ureteral obstruction can have a variety of causes intrinsic or extrinsic to the kidney. The effects of obstruction are examined from the perspectives of duration, severity, totality, and the presence of complicating factors. […] There is a difference in the postobstructive pathophysiology depending on whether one or both ureters were obstructed. Atrial natriuretic peptide may be important in postobstructive diuresis, and preliminary evidence suggests a role for it as protection against nephron ischemia in acute obstruction. […] The potential for recovery of renal function after relief of obstruction depends on the duration and degree of obstruction, the condition of the contralateral kidney, and the presence or absence of infection. Ability to acidify the urine to pH 6.0 preoperatively may be a good predictor of the recovery potential of an obstructed kidney. Urine concentrations of lysosomal enzymes such as N-acetylglucosaminidase also may be useful for this purpose, as may measurement of creatinine clearance in urine obtained from a nephrostomy tube.

• #19

  https://www.jci.org/articles/view/108167

  To investigate the pathogenesis of post-obstructive diuresis, a state of functional „anuria” during ureteral obstruction was created in awake rats by (a) bilateral obstruction (BO); (b) unilateral obstruction and contralateral nephrectomy (UO-Nx); or (c) unilateral obstruction and continuous i.v. reinfusion of urine from the intact contralateral kidney (UO-reinf). […] These results suggest that post-obstructive diuresis is due to one or more circulating diuretic factors that are normally excreted in the urine, and which, when retained (as in BO or UO-Nx rats) or returned to the circulation (as in UO-reinf rats), exert a diuretic effect. […] This result suggests that urea may be an important diuretic factor in post-obstructive diuresis, but does not exclude possible roles for other humoral factors.

• #20 Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-019-0234-2

  Chronic kidney disease (CKD) increases the risk and prevalence of cardiovascular disease (CVD) morbidity and mortality. […] However, the effect of unilateral ureteral obstruction (UUO) on the gut microbiome and circulating metabolites is unknown. […] In conclusion, UUO results in profound changes in the gut microbiome and circulating metabolites, events that contribute to the pathogenesis of inflammation and TIF. […] The unilateral ureteral obstruction (UUO) model is a well-established model of experimental chronic renal injury characterized by TIF. […] To dissect the effect of urinary tract obstruction from that of uremia on the microbiome and metabolome we used UUO, which, by promoting contralateral kidney hypertrophy, minimizes the accumulation of uremic toxins/metabolites. […] The gut microbial dysbiosis and the resulting dysregulation of metabolites and bacterial translocation contribute to the pathogenesis of TIF.

• #21 Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-019-0234-2

  The changes in the gut microbiota and dysregulation of plasma metabolites in this study pointed to an association of the gut microbial dysbiosis with altered metabolisms of glycerophospholipids, glycerolipids, fatty acyls, sterols, acyl carnitines, organic acids, amino acids, and amines. […] Uremic toxins are implicated in TIF through exacerbation of oxidative stress and inflammation. […] Therefore, gut microbial dysbiosis might be associated with TIF. […] The demonstrated toxicities of phenol conjugates on intestinal epithelial cells suggest that phenol conjugates are a potential driver of gut barrier alterations. […] This effect could be related to the observed expansion of Blautia, Oscillibacter, Intestinimonas, and Acetatifactor in the UUO rats because these taxa have been shown to produce indole, p-cresol, and tryptophan derivatives. […] Taken together, these observations indicated the detrimental role of bacteria producing toxic metabolites in TIF aggravation.

• #22

  https://journals.lww.com/md-journal/fulltext/2019/11010/ureteral_obstruction_and_hydronephrosis_caused_by.105.aspx

  Early diagnosis and treatment are essential for avoiding late complications. […] Invasive therapies rather than conservative treatments are preferred to remove the FBs and relieve obstruction. […] FB migration causing ureteral obstruction and hydronephrosis is rare. These cases are usually caused by ingestion and sexual motives. The patients may present with different clinical features according to the various position of FBs. Early and accurate diagnosis and treatment are essential to avoid late complications.

• #23 Obstructive Uropathy: From Etiopathology to Therapy | Mourmouris | World Journal of Nephrology and Urology

  https://wjnu.org/index.php/wjnu/article/view/154/99

  Emergency treatment of obstructive uropathy is needed in the presence of bilateral obstruction, urosepsis, uremia and hyperkalemia, persistent renal colic, worsening of hydronephrosis and renal impairment. […] Most researchers agree that obstruction remaining for more than 6 weeks results in the emergence of a degree of irreversible chronic renal disease. […] In obstructive uropathy, the understanding of the underlying pathophysiological changes may help to increase the clinical suspicion of both urologists and nephrologists.

• #24 Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction – Mercer University

  https://catalog.mercer.edu/discovery/fulldisplay?docid=cdi_kiss_primary_4122588&context=PC&vid=01GALI_MUM:MainLibrary&lang=en&adaptor=Primo%20Central&tab=MAINBLENDED&query=sub%2Cexact%2C%20Endoplasmic%20reticulum%20%2CAND&mode=advanced&offset=20

  The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.

• #25 Matrix Metalloproteinases in Ureteropelvic Junction Obstruction: Their Role in Pathogenesis and Their Use as Clinical Markers

  https://www.mdpi.com/2073-4409/14/7/520

  For some authors, the identification of the number of functioning nephrons could be predictive of the functional outcome or could be used as a prognostic indicator. […] Further elucidation of the molecular processes underlying the disease could help in the determination of early biomarkers that can help direct the therapeutic decisions necessary to prevent lesion progression and improve kidney remodeling after surgical correction of the obstruction.

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