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  • 951.
    Yahaya, Ismail
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Uthman, Olalekan A.
    Save the Youth Initiative, PO Box 3951, Kaduna North, Kaduna, Nigeria.
    Uthman, Muhammed Mubashir B.
    Save the Youth Initiative, PO Box 3951, Kaduna North, Kaduna, Nigeria.
    Interventions for HIV-associated nephropathy2013In: Cochrane Database of Systematic Reviews, ISSN 1469-493X, E-ISSN 1469-493X, no 1, p. Art. no. CD007183-Article, review/survey (Refereed)
    Abstract [en]

    Background Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common cause of end stage kidney disease (ESKD) in human immunodeficiency virus-1 (HIV-1) serotype patients and it mostly affects patients of African descent. It rapidly progresses to ESKD if untreated. The goal of treatment is directed toward reducing HIV-1 replication and/or slowing the progression of chronic kidney disease. The following pharmacological agents have been used for the treatment of HIVAN: antiretroviral therapy, angiotensin-converting enzyme inhibitors (ACEi), steroids and recently cyclosporin. Despite this, the effect of each intervention is yet to be evaluated. Objectives To evaluate the benefits and harms of adjunctive therapies in the management of HIVAN and its effects on symptom severity and all-cause mortality. Search methods In January 2012 we searched the Cochrane Renal Group's Specialised Register, AIDS Education Global Information System (AEGIS database), ClinicalTrial.gov, the WHO International Clinical Trials Registry Portal, and reference lists of retrieved articles without language restrictions. In our original review we searched CENTRAL, MEDLINE, EMBASE, and AIDSearch, in addition to contacting individual researchers, research organisations and pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs of any therapy used in the treatment of HIVAN. Data collection and analysis We independently screened the search outputs for relevant studies and to retrieve full articles when necessary. For dichotomous outcomes results were to be expressed as risk ratios with 95% confidence intervals, and for continuous scales of measurement the mean difference was to be used. Main results We identified four relevant ongoing studies: one is still ongoing; two have completed recruitment but are yet to be published; and the fourth study was suspended for unspecified reasons. No completed RCTs or quasi-RCTs were identified. We summarised and tabulated the data from the observational studies, however no formal analyses were performed. Authors' conclusions There is currently no RCT-based evidence upon which to base guidelines for the treatment of HIVAN, however three ongoing studies have been identified. Data from observational studies suggest steroids and angiotensin-converting enzyme inhibitors appear to improve kidney function in patients with HIVAN, however no formal analyses were performed in this review. This review highlights the need for good quality RCTs to address the effects of interventions for treating this group.

  • 952. Yavari, Nazila
    et al.
    Andersson-Engels, Stefan
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    An overview on preclinical and clinical experiences with photodynamic therapy for bladder cancer2011In: Canadian Journal of Urology, ISSN 1195-9479, Vol. 18, no 4, p. 5778-5786Article, review/survey (Refereed)
    Abstract [en]

    Photodynamic therapy (PDT) is one of the most interesting methods of photo treatment. In general, PDT is a modality for the treatment of non-muscle invasive tumors. PDT is very well suited in managing bladder cancer, as the bladder is accessible by endoscopy and the tumors are most often limited to the mucosa or sub-mucosa. PDT is likely more useful for patients with recurrent tumors after conventional therapies, as well as for patients with diffuse non-muscle invasive bladder carcinomas that are refractory to standard treatments before the commitment to radical extirpative surgery, particularly in patients at surgical high risk. The treatment of tumors with PDT includes three major parameters: presence of oxygen in tumor tissue, administration of a photosensitizer, and subsequent exposure to light. The PDT mechanism relies on the in situ generation of cytotoxic agents by the activation of a light-sensitive drug, resulting in cell death. In this review, we present past and current advances in the use of PDT with urinary bladder cancer and discuss the future roles for this type of therapy in the treatment of bladder cancer.

  • 953.
    Zachar, Rikke
    et al.
    Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.
    Al-Masbhadi, Ammar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Dimke, Henrik
    Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.
    Svenningsen, Per
    Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.
    Jensen, Boye L.
    Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, JB Winslosvej 21,3, DK-5000 Odense, Denmark.
    Carlström, Mattias
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and gamma-ENaC abundance in rat kidney2018In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 315, no 3, p. F547-F557Article in journal (Refereed)
    Abstract [en]

    Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that 1) in pediatric patients with UPJO the RAAS is activated before surgical relief of the obstruction; 2) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na transporters; and 3) the injured UPJO kidney allows aberrant filtration of plasminogen, leading to proteolytic activation of the epithelial Na channel gamma-subunit (gamma-ENaC). Hydronephrosis resulting from UPJO in pediatric patients and rats was associated with increased urinary plasminogen-to-creatinine ratio. In pediatric patients, plasma renin, angiotensin II, urine and plasma aldosterone, and urine soluble prorenin receptor did not differ significantly before or after surgery, or compared with controls. Increased plasmin-to-plasminogen ratio was seen in UPJO rats. Intact gamma-ENaC abundance was not changed in UPJO kidney, whereas low-molecular cleavage product abundance increased. The Na-Cl cotransporter displayed significantly lower abundance in the UPJO kidney compared with the nonobstructed contralateral kidney. The Na-K-ATPase alpha-subunit was unaltered. Treatment with an angiotensin-converting enzyme inhibitor (8 days, captopril) significantly lowered blood pressure in UPJO rats. It is concluded that the RAAS contributes to hypertension following partial obstruction of urine flow at the pelvo-ureteric junction with potential contribution from proteolytic activation of ENaC.

  • 954.
    Zanetti, Daniela
    et al.
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Rao, Abhiram
    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Assimes, Themistocles L.
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA.
    Montgomery, Stephen B.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion2019In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 95, no 5, p. 1197-1208Article in journal (Refereed)
    Abstract [en]

    Urine biomarkers reflecting kidney function and handling of dietary sodium and potassium are strongly associated with several common diseases including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Knowledge about the genetic determinants of these biomarkers may shed light on pathophysiological mechanisms underlying the development of these diseases. We performed genome-wide association studies of urinary albumin: creatinine ratio (UACR), urinary potassium: creatinine ratio (UK/UCr), urinary sodium: creatinine ratio (UNa/UCr) and urinary sodium: potassium ratio (UNa/UK) in up to 218,450 (discovery) and 109,166 (replication) unrelated individuals of European ancestry from the UK Biobank. Further, we explored genetic correlations, tissue-specific gene expression, and possible genes implicated in the regulation of these biomarkers. After replication, we identified 19 genome-wide significant independent loci associated with UACR, 6 each with UK/UCr and UNa/UCr, and 4 with UNa/UK. In addition to 22 novel associations, we confirmed several established associations, including between the CUBN locus and microalbuminuria. We detected high pairwise genetic correlation across the urinary biomarkers, and between their levels and several physiological measurements. We highlight GIPR, a potential diabetes drug target, as possibly implicated in the genetic control of urinary potassium excretion, and NRBP1, a locus associated with gout, as plausibly involved in sodium and albumin excretion. Overall, we identified 22 novel genome-wide significant associations with urinary biomarkers and confirmed several previously established associations, providing new insights into the genetic basis of these traits and their connection to chronic diseases.

  • 955.
    Zare, Reza
    et al.
    Vestre Viken HF Baerum Hosp, Dept Urol, Oslo, Norway.
    Grabe, Magnus
    Lund Univ, Skane Univ Hosp, Dept Urol, Malmo, Sweden.
    Hermann, Gregers G.
    Univ Copenhagen, Herlev & Gentofte Hosp, Dept Urol, Copenhagen, Denmark.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Can routine outpatient follow-up of patients with bladder cancer be improved?: A multicenter prospective observational assessment of blue light flexible cystoscopy and fulguration2018In: Research and Reports in Urology, ISSN 2253-2447, E-ISSN 1179-1551, Vol. 10, p. 151-157Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this prospective cohort study was to determine the feasibility of incorporating blue light flexible cystoscopy (BLFC) and biopsy/fulguration into routine outpatient follow-up of non-muscle invasive bladder cancer patients.

    Methods: The study included patients with non-muscle-invasive bladder cancer (NMIBC) who were scheduled for routine follow-up. Hexaminolevulinate was instilled in the outpatient department, and the bladder was examined under white light and then with BLFC. Biopsies were taken from all suspicious lesions. Small tumors and suspicious lesions were fulgurated on site; patients with larger lesions were referred to the operating room for resection.

    Results: The study included 69 patients, with a mean age of 70 years (range 33 -89 years) and a mean duration since NMIBC diagnosis of 8 years. Most patients had high-grade cancer at initial diagnosis (52/69) and were at high risk of recurrence (48/69). Two patients per hour could be assessed using outpatient BLFC. Preparation and instillation of hexaminolevulinate took less than 10 minutes per patient, and patients had an additional waiting time of 45 60 minutes following instillation, while the hexaminolevulinate solution was retained in the bladder before examination. Eleven patients had histologically confirmed tumors that were identified using both white light flexible cystoscopy and BLFC. An additional three patients had tumors that were identified by BLFC only: two with Ta tumors and one with carcinoma in situ. Of the 14 patients with confirmed tumors, 11 could be managed on site with fulguration, whereas three were referred to the operating room. No adverse events attributable to BLFC were reported.

    Conclusion: Routine outpatient management of patients with NMIBC using BLFC and onsite biopsy/fulguration is feasible, despite the additional time required for hexaminolevulinate instillation, and appears to allow early detection of recurrent lesions, which can be fulgurated without the need for hospitalization.

  • 956.
    Zelenina, Marina
    et al.
    Nordic Centre of Excellence for Research in Water Imbalance Related Disorders (WIRED), Department of Woman and Child Health, Karolinska Institute.
    Li, Yanhong
    Glorieux, Isabelle
    Arnaud, Catherine
    Cristini, Christelle
    Decramer, Stéphane
    Aperia, Anita
    Casper, Charlotte
    Urinary aquaporin-2 excretion during early human development2006In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 21, no 7, p. 947-952Article in journal (Refereed)
    Abstract [en]

    This study was undertaken to assess one of the determinants of kidney concentrating capacity, aquaporin-2 (AQP2), in order to understand the physiopathology of water balance in newborn babies. Urinary AQP2 excretion has been shown to be proportional to AQP2 level in the apical plasma membrane of the kidney collecting ducts and has been suggested as a marker of vasopressin (AVP) action. Urinary AQP2 excretion in the early postnatal period and at 3 weeks of age was measured in 123 neonates admitted during a 6-month period to the neonatal intensive care unit of the Children's Hospital of Toulouse, France. Clinical and biochemical data were collected for each child. During the first days after birth, higher urinary AQP2 was observed in boys than in girls (P=0.01) and positively correlated with urinary sodium/potassium (Na/K) ratio (r=0.33, P=0.01). When the babies had reached 3 weeks of age, urinary AQP2 was proportional to the gestational age at birth (r=0.33, P=0.0068) and daily weight gain (r=0.36, P=0.003). It did not correlate with urinary osmolality, which was overall very low in all babies. Urinary AQP2 was decreased in conditions of impaired renal function (r=-0.42, P=0.0005) and acidosis (P=0.03). Prenatal corticosteroid treatment had no significant impact on urinary AQP2 level. Our data show that urinary AQP2 correlates with the overall maturity of tubular function in human neonates. In babies at this early age, urinary AQP2 cannot serve as a direct marker of the renal action of AVP but reflects AQP2 expression level associated with different physiopathological conditions.

  • 957.
    Zelic, Renata
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Zugna, Daniela
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy ; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Bottai, Matteo
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden .
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    Fiano, Valentina
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Fiorentino, Michelangelo
    Pathology Service, Addarii Institute of Oncology, Sant’ Orsola-Malpighi Hospital, Bologna, Italy.
    Giunchi, Francesca
    Pathology Service, Addarii Institute of Oncology, Sant’ Orsola-Malpighi Hospital, Bologna, Italy.
    Grasso, Chiara
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Lianas, Luca
    Data-Intensive Com puting Division, Center for Advanced Studies, Research and Development in Sardinia, Pula, Italy.
    Mascia, Cecilia
    Data-Intensive Com puting Division, Center for Advanced Studies, Research and Development in Sardinia, Pula, Italy.
    Molinaro, Luca
    Division of Pathology, Azienda Os pedaliero-Universitaria Città della Salute e della Scienza Hospital, Turin, Italy .
    Zanetti, Gianluigi
    Data-Intensive Com puting Division, Center for Advanced Studies, Research and Development in Sardinia, Pula, Italy.
    Richiardi, Lorenzo
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Centro di Riferimento per l ’ Epidemiologia e la Prevenzione Oncologica (CPO) in Piemonte, Turin, Italy .
    Pettersson, Andreas
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Akre, Olof
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Estimation of Relative and Absolute Risks in a Competing-Risks Setting Using a Nested Case-Control Study Design: Example From the ProMort Study2019In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, no 6, p. 1165-1173Article in journal (Refereed)
    Abstract [en]

    In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.

  • 958. Zhang, Lu
    et al.
    Hu, Jin
    Zirakzadeh, Ali A .
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Medicine, Immunology and Allergy Unit, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Rosvall, Jesper
    Hedlund, Mats
    Hu, Ping Sheng
    P A Wallin, Robert
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Detection of micro-metastases by flow cytometry in lymph nodes from patients with penile cancer2018In: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 18, no 1, article id 86Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The tumor draining lymph node concept was first described in penile cancer for staging. Immunohistochemistry and histopathology evaluations are routinely used in clinical practice to examine lymph nodes for metastasis. However, these methods are time-consuming with low diagnostic accuracy and micro-metastases might be missed. In this study, we aim to evaluate detection of metastatic cells in draining lymph nodes by flow cytometry.

    METHODS: To assess the sensitivity of micro-metastasis detection by FACS (Fluorescence-activated cell sorting), HeLa cells were titrated into Peripheral blood mononuclear cells (PBMCs) and expression of pan-cytokeratin AE1/AE3 was analyzed. Single cell suspensions were separately prepared from 10 regional lymph nodes obtained from 5 patients with invasive penile cancer undergoing radical surgery and lymph node dissection. Lymph node dereived cells were examined for cell surface expression of EpCAM, E-cadherin and intracellular expression of pan-cytokeratin AE1/AE3 by FACS.

    RESULTS: Ten lymph nodes from 5 penile cancer patients were investigated in a head-to-head comparison between FACS and pathology examination of sections. All metastatic lymph nodes verified by pathology examination were also identified by FACS. Two additional lymph nodes with micro-metastases were diagnosed by FACS only.

    CONCLUSIONS: FACS analyses of pan-cytokeratin AE1/AE3 stained single cells from tumor draining lymph nodes can be used to detect micro-metastases in patients with penile cancer patients.

  • 959.
    Zhang, Rong
    et al.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Knapp, Michael
    Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany..
    Suzuki, Kentaro
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Kajioka, Daiki
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Schmidt, Johanna M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Inst Anat, Bonn, Germany..
    Winkler, Jonas
    Univ Bonn, Inst Anat, Bonn, Germany..
    Yilmaz, Oeznur
    Univ Bonn, Inst Anat, Bonn, Germany..
    Pleschka, Michael
    Univ Bonn, Inst Anat, Bonn, Germany..
    Cao, Jia
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Kockum, Christina Clementson
    Univ Lund Hosp, Dept Pediat Surg, Lund, Sweden..
    Barker, Gillian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Holmdahl, Gundela
    Queen Silvias Childrens Hosp, Dept Pediat Surg, Gothenburg, Sweden..
    Beaman, Glenda
    Univ Manchester, Ctr Genom Med, Manchester M13 9PL, Lancs, England..
    Keene, David
    Woolf, Adrian S.
    Univ Manchester, Manchester Acad Hlth Sci, Inst Human Dev, Manchester M13 9PL, Lancs, England.;Royal Manchester Childrens Hosp, Manchester, Lancs, England..
    Cervellione, Raimondo M.
    Cent Manchester Univ Hosp NHS Fdn Trust, Royal Manchester Childrens Hosp, Paediat Urol, Manchester, Lancs, England..
    Cheng, Wei
    Capital Inst Pediat, Dept Pediat Surg, Beijing, Peoples R China.;Monash Univ, Fac Med Nursing & Hlth Sci, Southern Med Sch, Dept Paediat, Clayton, Vic, Australia.;Monash Univ, Fac Med Nursing & Hlth Sci, Southern Med Sch, Dept Surg, Clayton, Vic, Australia.;Beijing United Family Hosp, Dept Surg, Beijing, Peoples R China..
    Wilkins, Simon
    Cabrini Monash Univ, Cabrini Hosp, Dept Surg, Melbourne, Vic, Australia.;Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Clayton, Vic 3800, Australia..
    Gearhart, John P.
    Johns Hopkins Sch Med, Div Pediat Urol, Baltimore, MD USA..
    Sirchia, Fabio
    Univ Torino, Citta Salute & Sci Univ Hosp, Dept Med Sci, Turin, Italy.;Univ Torino, Citta Salute & Sci Univ Hosp, Med Genet Unit, Turin, Italy..
    Di Grazia, Massimo
    IRCCS Burlo Garofalo, Inst Maternal & Child Hlth, Trieste, Italy..
    Ebert, Anne-Karolin
    Univ Hosp Ulm, Dept Urol & Pediat Urol, Ulm, Germany..
    Roesch, Wolfgang
    St Hedwig Hosp Barmherzige Bruder, Dept Pediat Urol, Regensburg, Germany..
    Ellinger, Joerg
    Univ Hosp Bonn, Dept Urol, Bonn, Germany..
    Jenetzky, Ekkehart
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;Johannes Gutenberg Univ Mainz, Dept Child & Adolescent Psychiat & Psychotherapy, Mainz, Germany..
    Zwink, Nadine
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Feitz, Wout F.
    Radboud Univ Nijmegen, Med Ctr, Pediat Urol Ctr, Dept Urol, Nijmegen, Netherlands..
    Marcelis, Carlo
    Radboud Univ Nijmegen, Med Ctr, Dept Genet, Nijmegen, Netherlands..
    Schumacher, Johannes
    Univ Bonn, Inst Human Genet, Bonn, Germany..
    Martinon-Torres, Federico
    Hosp Clin Univ Santiago, Translat Pediat & Infect Dis, Santiago De Compostela, Spain.;Inst Invest Sanitaria Santiago Santiago, GENVIP Res Grp Www Genvip Org, Galicia, Spain..
    Hibberd, Martin Lloyd
    Genome Inst Singapore, Singapore, Singapore..
    Khor, Chiea Chuen
    Univ Calif Davis, Med Ctr, Dept Pediat, Div Genom Med, Sacramento, CA 95817 USA..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Barth, Sandra
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany..
    Boyadjiev, Simeon A.
    Univ Calif Davis, Med Ctr, Dept Pediat, Div Genom Med, Sacramento, CA 95817 USA..
    Brusco, Alfredo
    Univ Torino, Citta Salute & Sci Univ Hosp, Dept Med Sci, Turin, Italy.;Univ Torino, Citta Salute & Sci Univ Hosp, Med Genet Unit, Turin, Italy..
    Ludwig, Michael
    Univ Bonn, Dept Clin Chem & Clin Pharmacol, Bonn, Germany..
    Newman, William
    Univ Manchester, Ctr Genom Med, Manchester M13 9PL, Lancs, England..
    Nordenskjold, Agneta
    Karolinska Univ Hosp, Astrid Lindgren Children Hosp, Pediat Surg, Stockholm, Sweden..
    Yamada, Gen
    Wakayama Med Univ, Inst Adv Med, Dev Genet, Wakayama, Japan..
    Odermatt, Benjamin
    Univ Bonn, Inst Anat, Bonn, Germany..
    Reutter, Heiko
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Childrens Hosp, Dept Neonatol & Pediat Intens Care, Bonn, Germany.;Univ Bonn, Bonn, Germany..
    ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42170Article in journal (Refereed)
    Abstract [en]

    Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

  • 960. Zheng, S. Lilly
    et al.
    Sun, Jielin
    Wiklund, Fredrik
    Gao, Zhengrong
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University Hospital, Umeå.
    Purcell, Lina D.
    Adami, Hans-Olov
    Hsu, Fang-Chi
    Zhu, Yi
    Adolfsson, Jan
    Johansson, Jan-Erik
    Turner, Aubrey R.
    Adams, Tamara S.
    Liu, Wennuan
    Duggan, David
    Carpten, John D.
    Chang, Bao-Li
    Isaacs, William B.
    Xu, Jianfeng
    Grönberg, Henrik
    Genetic variants and family history predict prostate cancer similar to prostate-specific antigen2009In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 15, no 3, p. 1105-1111Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Although prostate-specific antigen (PSA) is the best biomarker for predicting prostate cancer, its predictive performance needs to be improved. Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68. The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk. EXPERIMENTAL DESIGN: We systematically evaluated all prostate cancer risk variants that were identified from genome-wide association studies during the past year in a large population-based prostate cancer case-control study population in Sweden, including 2,893 prostate cancer patients and 1,781 men without prostate cancer. RESULTS: Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population. Using a cutoff of any 11 risk alleles or family history, the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86, respectively. The overall predictive performance of prostate cancer using genetic variants, family history, and age, measured by areas under curve was 0.65 (95% confidence interval, 0.63-0.66), significantly improved over that of family history and age (0.61%; 95% confidence interval, 0.59-0.62; P = 2.3 x 10(-10)). CONCLUSION: The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA. The utility of genetic testing, alone and in combination with PSA levels, should be evaluated in large studies such as the European Randomized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial.

  • 961.
    Zhou, Suhan
    et al.
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Jiang, Shan
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Guo, Jie
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Xu, Nan
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Wang, Qin
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Zhang, Gensheng
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Zhao, Liang
    Guangzhou Med Univ, Sch Basic Med Sci, Dept Physiol, Guangzhou, Guangdong, Peoples R China; Charite Univ Med Berlin, Inst Vegetat Physiol, Berlin, Germany.
    Zhou, Qin
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1,Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China.
    Fu, Xiaodong
    Guangzhou Med Univ, Sch Basic Med Sci, Dept Physiol, Guangzhou, Guangdong, Peoples R China.
    Li, Lingei
    Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA;Georgetown Univ, Hypertens Res Ctr, Washington, DC USA.
    Patzak, Andreas
    Charite Univ Med Berlin, Inst Vegetat Physiol, Berlin, Germany.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lai, En Yin
    Zhejiang Univ, Sch Med, Sch Basic Med Sci, Affiliated Hosp 1, Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China; Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA;Georgetown Univ, Hypertens Res Ctr, Washington, DC USA.
    ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function2019In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 1, p. F134-F145Article in journal (Refereed)
    Abstract [en]

    Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Set(473) and eNOS at Ser(1177). Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis. and improving microvascular endothelial dysfunction. rhADAMIS13 could be a promising strategy to treat AKI in clinical settings.

  • 962. Zhu, Baoyi
    et al.
    Ekman, Mari
    Svensson, Daniel
    Lindvall, Jessica M.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Lund University, Sweden.
    Nilsson, Bengt-Olof
    Uvelius, Bengt
    Swärd, Karl
    Array profiling reveals contribution of Cthrc1 to growth of the denervated rat urinary bladder2018In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 314, no 5, p. f893-f905Article in journal (Refereed)
    Abstract [en]

    Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold, and 2,890 mRNAs and 135 micro-RNAs (miRNAs) were differentially expressed. Comparison with array data from obstructed bladders demonstrated overlap between the conditions, and 10% of mRNAs changed significantly and in the same direction. Many mRNAs, including collagen triple helix repeat containing 1 (Cthrc1), Prc1, Plod2, and Dkk3, and miRNAs, such as miR-212 and miR-29. resided in the shared signature. Discordantly regulated transcripts in the two models were rare, making up for <0.07% of all changes, and the gene products in this category localized to the urothelium of normal bladders. These transcripts may potentially be used to diagnose sensory denervation. Western blotting demonstrated directionally consistent changes at the protein level, with increases of, e.g., Cthrc1, Prc1, Plod2, and Dkk3. We chose Cthrc1 for further studies and found that Cthrcl was induced in the smooth muscle cell (SMC) layer following denervation. TGF-beta 1 stimulation and miR-30d-5p inhibition increased Cthrc1 in bladder SMCs, and knockdown and overexpression of Cthrc1 reduced and increased SMC proliferation. This work defines common and distinguishing features of bladder denervation and obstruction and suggests a role for Cthrc1 in bladder growth following denervation.

  • 963. Zirakzadeh, A Ali
    et al.
    Kinn, Johan
    Krantz, David
    Rosenblatt, Robert
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
    Winerdal, Malin E
    Hu, Jin
    Hartana, Ciputra Adijaya
    Lundgren, Christian
    Bergman, Emma Ahlén
    Johansson, Markus
    Holmström, Benny
    Hansson, Johan
    Sidikii, Alexander
    Vasko, Janos
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marits, Per
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer2017In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, p. 63-70Article in journal (Refereed)
    Abstract [en]

    Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-α. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.

  • 964.
    Zirakzadeh, A. Ali
    et al.
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Kinn, Johan
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Krantz, David
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Rosenblatt, Robert
    Umeå Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden; Karolinska Inst, Stockholm South Gen Hosp, Dept Urol, Stockholm, Sweden.
    Winerdal, Malin E.
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Hu, Jin
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Lundgren, Christian
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Bergman, Emma Ahlén
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Sidikii, Alexander
    Länssjukhuset Ryhov, Dept Urol, Region Jonköping, Sweden.
    Vasko, Janos
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Marits, Per
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Sherif, Amir
    Umeå Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Winqvist, Ola
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer2017In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, p. 63-70Article in journal (Refereed)
    Abstract [en]

    Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-alpha. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.

  • 965. Zivkovic, AM
    et al.
    Yang, J
    Hegedus, C
    Nording, Malin
    Department of Entomology, University of California, Davis, CA, USA.
    O´Sullivan, A
    Hogg, RJ
    Weiss, RH
    Bay, C
    Hammock, BD
    Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations2012In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 8, no 6, p. 1102-1113Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease, frequently associated with hypertension and renal inflammation. ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil (FO) improve kidney function in animal models, but have inconsistent metabolic effects in humans. Oxylipin profiles in serum from IgAN patients supplemented with either FO or corn oil (CO) placebo were analyzed by liquid chromatography coupled to tandem mass spectrometry. EPA cyclooxygenase and lipoxygenase metabolites, and EPA and DHA epoxides and diols were increased in response to FO supplementation, as were total epoxides and epoxide/diol ratios. Several of these metabolites were drivers of separation as assessed by multivariate analysis of FO patients pre- vs. post-supplementation, including 17,18-dihydroxyeicosatrienoic acid, prostaglandin D3, prostagalandin E3, Resolvin E1, 12-hydroxyeicosapentaenoic acid, and 10(11)-epoxydocosapentaenoic acid. In patients whose proteinuria improved, plasma total oxylipins as well as several hydroxyoctadecadienoic acids, hydroxyeicosatetraenoic acids, and leukotriene B4 metabolites were among the metabolites that were significantly lower than in patients whose proteinuria either did not improve or worsened. These data support the involvement of oxylipins in the inflammatory component of IgAN as well as the potential use of oxylipin profiles as biomarkers and for assessing responsiveness to ω-3 fatty acid supplementation in IgAN patients.

  • 966.
    Ärnlöv, Johan
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Carlsson, Axel C
    Sundström, Johan
    Ingelsson, Erik
    Larsson, Anders
    Lind, Lars
    Larsson, Tobias E
    Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community2013In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 83, p. 160-166Article in journal (Refereed)
    Abstract [en]

    Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Longitudinal Study of Adult Men population-based cohort (mean age 77 years). During a median follow-up of 9.7 years, 110 participants died of cardiovascular causes. In Cox regression models adjusted for age and established cardiovascular risk factors, higher serum FGF23 was associated with a significantly increased risk for cardiovascular mortality (hazard ratio (HR) per increased s.d. of 1.36). This relationship remained significant, albeit attenuated, after adjustment for glomerular filtration rate (GFR) (HR 1.21). FGF23 was also associated with all-cause mortality, although the association was weaker than that with cardiovascular mortality, and it was nonsignificant in fully adjusted multivariate models. Spline analysis suggested a log-linear relationship between FGF23 and outcome. Participants with a combination of high FGF23 (>60 pg/ml), low GFR (<60 ml/min), and micro-/macro-albuminuria (albumin/creatinine ratio above 3 mg/ml) had an almost eightfold increased risk compared with participants without these abnormalities. Thus, a higher FGF23 level is associated with an increased cardiovascular mortality risk in the community. Clinical trials are needed to determine whether FGF23 is a modifiable risk factor.Kidney International advance online publication, 5 September 2012; doi:10.1038/ki.2012.327.

  • 967.
    Öborn, Helena
    et al.
    Division of Pediatrics, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Wettergren, Lena
    Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden.
    Herthelius, Maria
    Division of Pediatrics, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Forinder, Ulla
    University of Gävle, Faculty of Health and Occupational Studies, Department of Social Work and Psychology, Social work. Department of Neurobiology, Care Sciences and Society, Division of Social Work, Karolinska Institutet, Stockholm, Sweden.
    Associations between lower urinary tract dysfunction and health-related quality of life in children with chronic kidney disease2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 8, p. 959-966Article in journal (Refereed)
    Abstract [en]

    Aim Little is known about the health-related quality of life (HRQoL) of children with lower urinary tract dysfunction (LUTD) and chronic kidney disease (CKD). We investigated LUTD and other possible predictors of impaired HRQoL in children with conservatively treated moderate to severe CKD or with a kidney transplant.

    Methods All 64 children with CKD or a kidney transplant treated at Karolinska University Hospital, Stockholm, Sweden, between June 2011 and December 2012 were approached and 59 children aged 8-18 were enrolled in the study. Lower urinary tract function was evaluated with voiding history, frequency and volume chart, uroflowmetry and post void ultrasound measurements. Self-reported HRQoL was assessed with validated generic instruments.

    Results The HRQoL of the study cohort was as good as the general paediatric population, apart from the physical and psychological well-being dimensions, and was no different to children with other chronic conditions. Urinary incontinence, but not LUTD in general, was associated with impaired HRQoL, as was having a kidney transplant and being female in some dimensions.

    Conclusion LUTD was common in children with CKD or a kidney transplant but did not affect their general HRQoL. Predictors of impaired HRQoL included incontinence, having had a kidney transplant and being female.

  • 968.
    Örtegren, Joakim
    et al.
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden; epartment of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Holmberg, Jan Tage
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden; Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Lekås, Edvard
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden.
    Mana, Sabah
    Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Mårtensson, Stig
    Section of Urology, Department of Surgery, Växjö County Hospital, Växjö, Sweden; Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Richthoff, Jonas
    Section of Urology, Department of Surgery, Ljungby Hospital, Ljungby, Sweden.
    Sundqvist, Pernilla
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology , Sahlgrenska University Hospital, Gothenburg, Sweden .
    Bratt, Ola
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology , Sahlgrenska University Hospital, Gothenburg, Sweden .
    Liedberg, Fredrik
    Department of Translational Medicine, Lund University , Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    A randomised trial comparing two protocols for transrectal prostate repeat biopsy: six lateral posterior plus six anterior cores versus a standard posterior 12-core biopsy2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Objective: To test the hypothesis that a combination of 6 posterior and 6 anterior cores detects more cancer than 12 posterior cores at a repeat transrectal prostate biopsy in men who have had one previous benign systematic biopsy.

    Patients and methods: Three hundred and forty men with persistently raised serum PSA were randomly allocated 1:1 to either a standard 12-core biopsy (12 cores from the lateral peripheral zone through a side-fire biopsy canal) or an experimental 12-core biopsy protocol with 6 anterior cores through an end-fire biopsy canal and 6 cores from the lateral peripheral zone through a side-fire biopsy canal. All biopsies were obtained transrectally with ultrasound guidance. The primary endpoint was cancer detection. Secondary endpoints were detection of ISUP Grade Groups/Gleason Grade Group ≥2 cancer, total biopsy cancer length and complications leading to medical intervention.

    Results: Prostate cancer was detected in 42/168 men (25%) in the experimental biopsy group and in 36/172 (21%) in the standard biopsy group (p = 0.44). The corresponding proportions for Gleason score ≥7 were 12% and 7% (p = 0.14). Median total cancer length was 4 (inter quartile range [IQR] = 1.5 - 6) mm in the end-fire group and 3 (IQR = 1.3 - 7) mm in the side-fire group. Ten men in the end-fire group and three in the side-fire group had a medical intervention for biopsy-related complications (p = 0.05).

    Conclusion: The biopsy protocol that included six end-fire anterior cores did not detect more cancer and was associated with more complications.

17181920 951 - 968 of 968
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