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Fibrosis is the end point of most renal diseases, and several glycosaminoglycans have been shown to attenuate this process. Marine invertebrate glycosaminoglycans with unique structures have opened the possibility to test these new compounds on renal fibrosis. The effect of a fucosylated chondroitin sulfate from an echinoderm marine species is reported with the use of a model of renal fibrosis in rats, termed unilateral ureteral obstruction. Animals were given 4 mg/kg body wt of fucosylated chondroitin sulfate intraperitoneally, once a day. After 14 days, their kidneys were examined by histological, immunohistochemical, and biochemical methods. Compared with control mice, collagen deposition decreased in the course of renal fibrosis in the animals receiving fucosylated chondroitin sulfate, as revealed by Sirius red staining and hydroxyproline content. The cellularity related to myofibroblasts and macrophages was also reduced, as was the production of transforming growth factor (TGF)-[beta]. The glycosaminoglycan content increased in the renal interstitium of animals submitted to unilateral ureteral obstruction compared with the control contralateral kidney, mostly due to an increase of chondroitin sulfate content. Interestingly, no change in the pattern of glycosaminoglycan deposition was observed after administration of fucosylated chondroitin sulfate. Fibrosis induced by unilateral ureteral obstruction is attenuated in P-selectin-deficient mice, which also do not respond to the invertebrate glycosaminoglycan. In conclusion, fucosylated chondroitin sulfate attenuates renal fibrosis on a ureteral obstruction model in mice preponderantly through a P-selectin-mediated mechanism. glycosaminoglycans; inflammatory cells; anti-selectin activity; cytokine expression; collagen accumulation doi: 10.1152/ajprenal.00217.2010

Ureteral obstruction leads to increased pressure and inducible nitric oxide synthase (iNOS) expression. This study examined the involvement of epidermal growth factor (EGF) receptor (EGFR), nuclear factor-[kappa]B (NFKB), and signal transducers and activators of transcription 3 (STAT3) in iNOS induction in human proximal tubule (HKC-8) cells in response to pressure or EGF. HKC-8 cells were subjected to 60 mmHg pressure or treated with EGF for 0-36 h. iNOS was more rapidly induced in response to EGF than pressure. The addition of EGFR, NF[kappa]B, and STAT3 inhibitors significantly suppressed pressure- or EGF-stimulated iNOS mRNA and protein expression. Analysis of the activated states of EGFR, NF[kappa]B p65, and STAT3 after exposure to both stimuli demonstrated phosphorylation within 2.5 rain. Anti-EGF antibody inhibited iNOS induction in pressurized HKC-8 cells, providing evidence that endogenous EGF mediates the response to pressure. In ureteral obstruction, when pressure is elevated, phosphorylated EGFR was detected in the apical surface of the renal tubules, validating the in vitro findings. These data indicate that EGFR, NF[kappa]B, and STAT3 are required for human iNOS gene induction in response to pressure or EGF, indicating a similar mechanism of activation. cytokine mix; cycloheximide

Byline: Stefan Jochberger (1), Corinna Velik-Salchner (1), Viktoria D. Mayr (1), Gunter Luckner (1), Volker Wenzel (1), Gerda Falkensammer (2), Hanno Ulmer (3), Nils Morgenthaler (4), Walter Hasibeder (5), Martin W. Dunser (1) Keywords: Cardiac surgery; Vasodilatory shock; Plasma levels; Vasopressin; Copeptin Abstract: Objective To evaluate arginine vasopressin (AVP) and copeptin plasma concentrations in patients with vasodilatory shock after cardiac surgery. Design Prospective, controlled, clinical study. Setting Surgical intensive care unit and cardiac surgery ward in a tertiary university teaching hospital. Patients and participants Thirty-three critically ill patients with vasodilatory shock after cardiac surgery and ten control patients undergoing uncomplicated aorto-coronary bypass surgery. Measurements and results Hemodynamic, laboratory and clinical data were recorded daily in all patients during the first 7 days after cardiac surgery. At the same time, points blood was withdrawn to determine plasma concentrations of AVP (radioimmunoassay) and copeptin (immunoluminometric assy). Standard tests, a mixed effects model and regression analyses were used for statistical analysis. The course of AVP was significantly different between groups (P < 0.001). While AVP concentrations were lower in the study group on the first postoperative day, they were higher than that in the control group from postoperative day 3 on. There was no difference in the postoperative AVP response between study patients with or without chronic angiotensin-converting enzyme inhibitor therapy. Except during continuous veno-venous hemofiltration, AVP and copeptin correlated significantly with each other (P < 0.001 r = 0.749). Conclusions The AVP response to cardiac surgery is significantly different between patients with vasodilatory shock and patients undergoing uncomplicated aorto-coronary bypass surgery. Although no causative relationship between AVP concentrations and cardiovascular instability can be drawn from these results, our data support the hypothesis that inadequately low AVP plasma levels contribute to the failure to restore vascular tone in vasodilatory shock after cardiac surgery. Author Affiliation: (1) Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria (2) Institute for Medical and Chemical Laboratory Diagnostics, Innsbruck Medical University, Innsbruck, Austria (3) Department of Medical Statistics, Informatics and Health Economics (MSIG), Innsbruck Medical University, Innsbruck, Austria (4) Department of Research, B.R.A.H.M.S. Aktiengesellschaft, Hennigsdorf, Germany (5) Department of Anesthesiology and Critical Care Medicine, Krankenhaus der Barmherzigen Schwestern, Ried im Innkreis, Austria Article History: Registration Date: 01/09/2008 Received Date: 28/11/2007 Accepted Date: 31/07/2008 Online Date: 30/09/2008 Article note: Parts of this work were presented as an abstract at the 20th Congress of the European Society of Intensive Care Medicine in Berlin, 7--10 October 2007.

Obstruction-induced fibrosis is a leading cause of end-stage renal failure in children. The pathophysiological mechanisms may involve apoptosis and the rennin-angiotensin system. We studied apoptosis and fibrosis in a well-established neonatal pig model with unilateral partial ureteral obstruction (PUUO) induced during ongoing nephrogenesis in 2-day-old piglets. The role of angiotensin II (ANG II) was studied using the A[T.sub.1] receptor blocker CV-11974 (0.12 mg/h candesartan from age 23 to 30 days). At day 30 the kidneys were perfusion fixed and fibrosis, apoptosis, and tubular lengths were quantitated using stereological methods, picro Sirius red staining, and immunohistochemical techniques identifying activated caspase 3, aquaporin-2 (AQP2), and yon Willebrand factor. The collagen content was assessed by hydroxyproline density. Neonatal induced PUUO increased interstitial and glomerular cell apoptosis and fibrosis. At this stage, PUUO did not increase tubular cell apoptosis or decrease tubular length and cell number. A[T.sub.1] receptor blockade prevented the PUUO-induced interstitial and glomerular cell apoptosis but did not attenuate fibrosis. In conclusion, A[T.sub.1] receptor blockade after the end of nephrogenesis may prevent interstitial and glomerular cell apoptosis but not fibrosis, suggesting that pathways not involving A[T.sub.1] receptor stimulation contribute to neonatal obstruction-induced fibrosis or that prevention of interstitial cell apoptosis counteracts a potential antifibrotic effect of A[T.sub.1] receptor blockade in this pig model of congenital obstructive nephropathy. Our results demonstrate that ANG II plays a role in PUUO-induced glomerular cell apoptosis. angiotensin II; caspase 3; neonatal; stereology; tubular doi:10.1152/ajprenal.00479.2006.

Abstract The rates of ureteric obstruction and complications for use of externally draining uretero-vesico-cutaneous (external) stents (Group 1: n=39) and the use of internal uretero-vesical (double-J) stents (Group 2: n=16), [...]

Byline: S. K. Chowdhary (1), A. Lander (1), K. Parashar (1), J. J. Corkery (1) Keywords: Keywords Ectopic ureters; Solitary kidney Abstract: Ectopic ureters present in childhood with symptoms related to an abnormal site or structure (refluxing, obstructed) of the ureteric orifice. The majority drain duplex kidneys. The diagnosis is relatively easy if the poles are functioning or hydronephrotic. Associated malformations are rarely seen and the results of surgery are gratifying. If an ectopic ureter drains a single kidney, it is called a single-system ectopic ureter (SSEU). We reviewed a 15-year experience (1980--1995) with 127 ectopic ureters from our hospital:11 SSEUs in ten consecutive children were managed during this period. Our data lead us to believe that SSEUs are a special subset of ectopic ureters. Diagnosis is often delayed because the ectopic ureter may be associated with a single small, dysplastic, poorly-functioning, non-visualised kidney and the child may be thought to have a contralateral normal 'solitary kidney'. Associated systemic malformations are common. Residual symptoms of wetting may persist in the early postoperative period. A high degree of suspicion must be maintained for this entity when a child presents with urinary symptoms of wetting or recurrent infection and a 'solitary kidney'. Early endoscopic examination of the genitourinary tract will clinch the diagnosis in the majority of cases. Residual symptoms of wetting in the postoperative period generally resolve with passage of time. Author Affiliation: (1) Diana, Princess Of Wales Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK, GB (2) Advanced Paediatric Centre, PGIMER, Chandigarh 160012, India, IN Article note: Accepted: 20 November 2000

Herniation of a ureter in an inguinal canal and scrotum is rare, and the general surgeon should be aware of this possibility to avoid injury to the ureter during hernial [...]