Project description:BackgroundPediatric hydronephrosis induced by pelvic-ureteric junction obstruction (PUJO) is treated by dismembered pyeloplasty (DP) via open and laparoscopic surgery. The etiology of PUJO involves both intrinsic stenosis and extrinsic compression of crossing vessels (CVs). PUJO owing to CVs is also treated by DP, as there is no consensus concerning this vascular condition. We encountered a 2-year-old infant with pure extrinsic PUJO combined with horseshoe kidney who successfully underwent laparoscopic transposition for CVs (vascular hitch).Case presentationA 2-year-old boy was prenatally diagnosed with left multicystic dysplastic kidney (MDCK) and right hydronephrosis and received a definitive diagnosis after birth. At 6 months old, renal scintigraphy revealed a non-functioning pattern in the left kidney and an obstructive pattern in the right, showing no response to furosemide loading. The patient also had recurrent urinary tract infection, and his right hydronephrosis gradually worsened. We decided to perform surgery for the right PUJO. Preoperative enhanced computed tomography detected three right renal vessels independently branching from the abdominal aorta. The middle renal vessels were located at the ventral side of the pelvis and coincident with the site of PUJO. These vessels were suspected of being CVs. The patient underwent laparoscopic surgery electively. A 5-mm trocar was inserted at the umbilicus for a 5-mm, 30° rigid scope. Two additional ports were then inserted under laparoscope inspection. The dilated right pelvis and CVs were detected after ascending colon mobilization. To confirm the pathogenesis of PUJO, the CVs were dissected and taped. After taping the CVs, an intraoperative diuretic test was performed using furosemide loading. Peristalsis of the right ureter was recognized, and the extrinsic PUJO owing to the CVs was definitively confirmed. We therefore performed transposition for the CVs (vascular hitch procedure). The CVs were mobilized in the cranial direction and those were wrapped by dilated pelvis. The post-operative course was uneventful. The renal scintigraphy findings improved and showed a favorable response of furosemide loading.ConclusionsThe laparoscopic vascular hitch procedure is minimally invasive and effective for extrinsic PUJO due to CVs. Anastomotic stricture after Anderson and Hynes DP can be prevented by appropriate patient selection.
Project description:Arabic gum (AG) has antioxidant and anti-inflammatory properties. However, the effect of AG in ureteric obstruction (UO) has not been investigated yet. Male rats underwent reversible left unilateral UO (UUO) for 72 h. Group AG-1 (n = 12) received AG 15 g/kg/day dissolved in drinking water starting seven days before and continuing throughout the period of the UUO, whereas group Vx-1 (n = 8) had only water. Group AG-2 (n = 12) and Vx-2 (n = 8) had similar protocols as AG-1 and Vx-1, respectively, but underwent terminal experiments to measure renal functions, six days post-UUO reversal. Arabic gum significantly attenuated the UUO-induced increase in the tissue level of malonedialdehyde and superoxide dismutase and the rise in the gene expression of TNF-?, TGF-?1, and p53 in AG-1 compared to Vx-1. It also attenuated the severity of tubular dilatation. However, AG did not affect the alterations in the renal blood flow or glomerular filtration rate. The fractional sodium excretion was lower in AG-2 but did not reach statistical significance (0.40 ± 0.11 vs 0.74 ± 0.12, p = 0.07). AG attenuated the UUO-induced rise in oxidative stress markers and proinflammatory and profibrotic cytokines and the degree of renal tubular dilatation, indicating a protective effect in obstructive nephropathy.
Project description:Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.
Project description:Introduction: Epigenetic regulation of fibrogenesis through post-translational histone modifications (marks) may be a key determinant of progression in renal disease. In this study, we examined the distribution and acquisition of histone 3 Lysine 9 (H3K9) marks after injury and stimulation with the pro-fibrotic cytokine TGF-β1. Our focus was on their presence in activated fibroblasts (myofibroblasts) and epithelial cells (epithelial-mesenchymal transition). Methods and Results: Immunofluorescent microscopy was used to examine global H3K9 acetylation (H3K9Ac) and tri-methylation (H3K9Me3) after unilateral ureteric obstruction (UUO) in mice. Confocal, super resolution microscopy and flow cytometry were used to determine the in vitro effect of TGF-β1 on structural arrangement of these marks, and their relationship with α-smooth muscle actin (αSMA) expression, a marker of myofibroblasts and early EMT. The number of individual histone marks was increased 10 days after UUO (p < 0.05 vs. control), with both marks clearly seen in various cell types including proximal tubules and myofibroblasts. Sub-nuclear microscopy in primary rat renal fibroblasts and a proximal tubule cell line (NRK-52e) showed that H3K9Ac was co-localized with phosphorylated-Ser2 RNA polymerase II (pRNAPol II), while H3K9Me3 was not, consistent with permissive and repressive effects on gene expression respectively. In both cell types H3K9Ac was diffusely distributed throughout the nucleus, while H3K9Me3 was found in compartments resembling the nucleolus, and in the case of the fibroblast, also juxtapositioned with the nuclear membrane. TGF-β1 had no effect on H3K9Ac marks in either cell, but resulted in a redistribution of H3K9Me3 within the fibroblast nucleus. This was unrelated to any change in mitogenesis, but was associated with increased αSMA expression. Conclusion: These findings highlight why it is important to consider the epigenetics of each cell individually, because whilst no overall enrichment occurred, renal myofibroblast differentiation was accompanied by distinct changes in histone mark arrangements.
Project description:Memokath-051 is a thermo-expandable, nickel-titanium alloy spiral stent used to treat ureteric obstruction resulting from malignant or benign strictures. The National Institute for Health and Care Excellence (NICE) selected Memokath-051 for evaluation. The company, PNN Medical, claimed Memokath-051 has clinical superiority and cost savings compared with double-J stents. It identified five studies reporting clinical evidence on Memokath-051 and constructed a de novo cost model comparing Memokath-051 to double-J stents. Results indicated that Memokath-051 generated cost savings of £4156 per patient over 2.5 years. The External Assessment Centre (EAC) critiqued the company's submission and completed substantial additional work. Sixteen studies were identified assessing Memokath-051 and all listed comparators in the scope (double-J stents, reconstructive surgery and metallic and alloy stents) except nephrostomy. Similar success rates were reported for Memokath-051 compared with double-J and Resonance stents and worse outcomes compared with other options with evidence available. The EAC updated the company's cost model structure and modified several inputs. The EAC's model estimated that Memokath-051 generated savings of at least £1619 per patient over 5 years compared with double-J stents, was cost neutral compared with other metallic stents and was cost saving compared with surgery up to month 55. Overall, Memokath-051 is likely to be cost saving in patients not indicated for reconstructive surgery and those expected to require a ureteral stent for at least 30 months. The Medical Technologies Advisory Committee (MTAC) reviewed the evidence and supported the case for adoption, issuing partially supportive recommendations published after public consultation as Medical Technologies Guidance 35.
Project description:A 37-year-old woman receiving in vitro fertilisation (IVF) treatment presented with lethargy, fevers and anuria. Her background included complex surgically managed Crohn's disease and mild right-sided hydronephrosis (with no evidence of obstruction on MAG3 renogram). On examination, she had a distended abdomen with generalised tenderness. Blood tests revealed an acute kidney injury and confirmed sepsis. She was found to have bilateral ureteric obstruction with worsening of the right-sided hydronephrosis and new-onset left-sided hydronephrosis secondary to bilateral ovarian masses, diagnosed as mild ovarian hyperstimulation syndrome (OHSS). She was initially managed with fluid resuscitation, bilateral nephrostomies, antibiotics and supportive management of mild OHSS. She made a good recovery and was discharged after placement of antegrade stents and removal of nephrostomies. On follow-up, following resolution of ovarian hyperstimulation, she has been diagnosed with a right-sided distal ureteric stricture and is awaiting reconstruction. Her left ureteric stent has been removed.
Project description:BackgroundTo compare quality of life (QoL) indices between ureteral stent (DJS) and nephrostomy tube (PCN) inserted in the setting of acute ureteral obstruction.MethodsProspective bi-centered study. Over the span of 2?years, 45 DJS and 30 PCN patients were recruited. Quality of life was assessed by 2 questionnaires, EuroQol EQ-5D and 'Tube symptoms' questionnaire, at 2 time points (at discharge after drainage and before definitive treatment).ResultsPatients' demographics and pre-drainage data were similar. There were no clinically significant differences in patient's recovery between the groups, including post procedural pain, defeverence, returning to baseline renal function, and septic shock complications. More DJS patients presented to the emergency room with complaints related to their procedure compared to PCN patients. At first, DJS patients complained more of urinary discomfort while PCN patients had worse symptoms relating to mobility and personal hygiene, with both groups achieving similar overall QoL score. At second time point, PCN patients' symptoms ameliorated while symptoms in the DJS group remained similar, translating to higher overall QoL score in the PCN group.ConclusionsThe two techniques had a distinct and significantly different impact on quality of life. Over time, PCN patients' symptoms relieve and their QoL improve, while DJS patients' symptoms persist. Specific tube related symptoms, and their dynamics over time, should be a major determinant in choosing the appropriate drainage method, especially when definitive treatment is not imminent.
Project description:Vascular lesions of gut are rare and they may rarely cause luminal obstruction in neonates. A baby boy born at 36 weeks of gestation presented with small bowel obstruction on day 3 of life. X-ray suggested small bowel obstruction. Contrast enema showed microcolon with multiple filling defects. Exploration revealed thin floppy gut with multiple segments of stenoses and dilatation with surface bluish discoloration but no perforation, two areas were resected. Proximal anastomosis was done and distally a stoma was formed. Histopathology showed vascular malformation in all the layers of gut. The diagnosis was impossible preoperatively and could be established after surgery only.
Project description:BackgroundUnilateral ureteric-pelvic junction obstruction (UPJO) is the most common cause of obstructive uropathy and may lead to renal impairment and loss of renal function. The current diagnostic approach with renal imaging cannot reliably determine which newborns and infants less than two years of age have a significant obstruction and are at risk for permanent kidney damage. There is therefore no consensus on optimal therapeutic management of unilateral UPJO.ObjectivesTo assess the effects of surgical versus non-surgical treatment options for newborns and infants less than two years of age with unilateral UPJO.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2016), MEDLINE/Ovid, and EMBASE/Ovid databases from their inception to 13 June 2016. We searched the reference lists of potentially relevant studies without using any language restriction. We also searched the following trial registers for relevant registered studies: www.clinicaltrials.gov/; ISRCTN registry (controlled-trials.com/); www.trialscentral.org/; apps.who.int/trialsearch/; www.drks.de/; and www.anzctr.org.au/trialSearch.aspx.Selection criteriaWe selected randomised and quasi-randomised controlled trials comparing surgical with non-surgical interventions for the treatment of unilateral UPJO.Data collection and analysisTwo review authors independently assessed study eligibility and risk of bias of included studies and extracted data. In case of disagreements we consulted a third review author. The data reported in the two included studies did not allow us to perform a meta-analysis.Main resultsWe found only two studies at high risk of bias that were eligible for inclusion in this review. The total sample size, including both trials, was small (n = 107 participants less than six months of age from the UK and USA), and not all prespecified outcome measures were assessed. Reported measures only accounted for the short-term follow-ups. The mean split renal function was not statistically different between the surgical and non-surgical group at the six-month or one-year time point (very low-quality evidence). The surgical group showed a significantly less obstructed drainage pattern and a lower urinary tract dilatation than the non-surgical group (very low-quality evidence). Transfer from the non-surgical group to the surgical group was reported for about one out of five participants. Split renal function after secondary surgical intervention was reported with variable results, but most of the participants reverted to pre-deteriorated values. The studies either provided no or insufficient data on the following outcome measures: postoperative complications, UPJO-associated clinical symptoms, costs of interventions, radiation exposure, quality of life, and adverse effects.Authors' conclusionsWe found limited evidence assessing the benefits and harms of surgical compared to non-surgical treatment options for newborns and infants less than two years of age with unilateral UPJO. The majority of participants in the non-surgical treatment group did not experience any significant deterioration of split renal function, and only about 20% of them underwent secondary surgical intervention, with minor risk of permanent deteriorated split renal function. The study follow-up period was too short to assess the long-term effects on split renal function in both treatment groups. We need further randomised controlled trials with sufficient statistical power and an adequate follow-up period to determine the optimal therapy for newborns and infants less than two years of age with unilateral UPJO.