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  • 151.
    Draaken, Markus
    et al.
    Institute of Human Genetics, University of Bonn, Germany.
    Baudisch, Friederike
    Timmermann, Bernd
    Kuhl, Heiner
    Kerick, Martin
    Proske, Judith
    Wittler, Lars
    Pennimpede, Tracie
    Ebert, Anne-Karoline
    Rösch, Wolfgang
    Stein, Raimund
    Bartels, Enrika
    von Lowtzow, Catharina
    Boemers, Thomas M
    Herms, Stefan
    Gearhart, John P
    Lakshmanan, Yegappan
    Kockum, Christina Clementsson
    Holmdahl, Gundela
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nordenskjöld, Agnetha
    Boyadjiev, Simeon A
    Herrmann, Bernhard G
    Nöthen, Markus M
    Ludwig, Michael
    Reutter, Heiko
    Institute of Human Genetics, University of Bonn, Germany.
    Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region2014In: Birth defects research. Clinical and molecular teratology, ISSN 1542-0752, E-ISSN 1542-0760, Vol. 100, no 6, p. 512-517Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients.

    METHODS: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls.

    RESULTS: New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes.

    CONCLUSION: Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation.

  • 152. Drechsler, Christiane
    et al.
    Philstrom, Hege
    Meinitzer, Andreas
    Pilz, Stefan
    Tomaschitz, Andreas
    Abedini, Sadollah
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Jardine, Alan
    Wanner, Christoph
    Maerz, Winfried
    Holdaas, Hallvard
    Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results from the Alert Study2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 539-539Article in journal (Other academic)
  • 153. Drechsler, Christiane
    et al.
    Pihlström, Hege
    Meinitzer, Andreas
    Pilz, Stefan
    Tomaschitz, Andreas
    Abedini, Sadollah
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Jardine, Alan G
    Wanner, Christoph
    März, Winifred
    Holdaas, Hallvard
    Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results From the Assessment of Lescol in Renal Transplantation Study2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 7, p. 1470-1476Article in journal (Refereed)
    Abstract [en]

    Background: Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.

    Methods: Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).

    Results: Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 µmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 µmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 µmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13–5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36–4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63–10.69) and 2.50 (95% CI, 1.38–4.55), respectively.

    Conclusions: Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.

  • 154.
    Dubois, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ronquist, K Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ek, Bo
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Proteomic profiling of detergent resistant membranes (lipid rafts) of prostasomes2015In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 14, no 11, p. 3015-3022Article in journal (Refereed)
    Abstract [en]

    Prostasomes are exosomes derived from prostate epithelial cells through exocytosis by multivesicular bodies. Prostasomes have a bilayered membrane and readily interact with sperm. The membrane lipid composition is unusual with a high contribution of sphingomyelin at the expense of phosphatidylcholine and saturated and monounsaturated fatty acids are dominant. Lipid rafts are liquid-ordered domains that are more tightly packed than the surrounding non-raft phase of the bilayer. Lipid rafts are proposed to be highly dynamic, submicroscopic assemblies that float freely within the liquid disordered membrane bilayer and some proteins preferentially partition into the ordered raft domains. We asked the question whether lipid rafts do exist in prostasomes and, if so, which proteins might be associated with them. Prostasomes of density range 1.13-1.19g/mL were subjected to density gradient ultracentrifugation in sucrose fabricated by phosphate buffered saline (PBS) containing 1% Triton X-100 with capacity for banding at 1.10g/mL, i.e. the classical density of lipid rafts. Prepared prostasomal lipid rafts (by gradient ultracentrifugation) were analyzed by mass spectrometry and electron microscopy. The clearly visible band on top of 1.10g/mL sucrose in the Triton X-100 containing gradient was subjected to LC-MS/MS and more than 370 lipid raft associated proteins were identified. Several of them were involved in intraluminal vesicle formation, e.g. tetraspanins, ESCRTs and Ras-related proteins. This is the first comprehensive LC-MS/MS profiling of proteins in lipid rafts derived from exosomes. Data are available via ProteomeXchange with identifier PXD002163.

  • 155.
    Dubois, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Kharaziha, Pedram
    Chioureas, Dimitris
    Meersman, Niels
    Panaretakis, Theocharis
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Malignant Cell-Derived Extracellular Vesicles Express Different Chromogranin Epitopes Compared to Prostasomes2015In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, no 10, p. 1063-1073Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Prostasomes are nanosized extracellular vesicles exocytosed by prostate epithelial cells. They have been assigned many roles propitious to sperm in favor of fertilization. Prostatic cancer cells can also produce and secrete extracellular vesicles. METHODS. We assessed using ELISA, the surface expression of chromogranin proproteins on prostasomes and malignant extracellular vesicles of four different prostate cancer cell-lines, two hormone sensitive and two hormone refractory. We used a panel of chromogranin A and chromogranin B antibodies against peptides in-between hypothetical cleavage sites along the proproteins. RESULTS. A diverging pattern of chromogranin peptides was apparent when comparing prostasomes and malignant extracellular vesicles indicating a phenotypical change. We also compared western blot patterns (prostasomes and malignant extracellular vesicles) for selected antibodies that displayed high absorbances in the ELISA. Western blot analyses revealed various cleavage patterns of those proproteins that were analyzed in prostasomes and extracellular vesicles. CONCLUSION. Chromogranins are constituents of not only prostasomes but also of malignant prostate cell-derived extracellular vesicles with different amino acid sequences exposed at the membrane surface giving rise to a mosaic pattern. These findings may be of relevance for designing new assays for detection or even possible treatment of prostate cancers.

  • 156.
    Duchek, Milos
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jahnson, Staffan
    Mestad, Oddvar
    Hellström, Pekka
    Hellsten, Sverker
    Malmström, Per-Uno
    Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study.2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed.

    OBJECTIVE: To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours.

    DESIGN, SETTING, AND PARTICIPANTS: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr.

    MEASUREMENTS: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented.

    RESULTS AND LIMITATIONS: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination.

    CONCLUSIONS: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 157. Duranton, Flore
    et al.
    Palma, Alfonso
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wauthier, Michel
    Torres, Armando
    Argilés, Angel
    Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of Different Latitudes2018In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 43, no 5, p. 1529-1538Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Climate influences the regulation of blood pressure (BP). Our objective was to precisely estimate BP seasonality in hemodialysis (HD) patients from five European cities with marked climate differences. Methods: Stable prevalent HD patients from 5 European facilities (Santa Cruz de Tenerife (Spain), Seville (Spain), Montpellier (France), Ottignies (Belgium), Umea (Sweden)) present over the years 1995-1999 were included in this historical longitudinal observational study. Individual monthly averages of pre-dialysis BP level were computed from all facility BP measurements (>90 000 observations). The association between BP level and location, seasons and meteorological measurements was analyzed by mixed models. Results: 261 patients were included and followed-up for a median duration of 2 years (6903 monthly observations). Pre-dialysis SBP and DBP were minimal in summer (July) and maximal in winter (November and December), and mean changes were respectively 4.2 [3.0;5.4] and 2.0 [1.3;2.7] mmHg. Seasonality was confirmed in 4 locations (P-season <= 0.0010.001 for SBP and DBP), but not in Umea (both P-season >0.05). Seasonal changes in DBP were larger in southern locations (P-interaction =0.02). BP level was associated with climate parameters: in a positive manner with humidity or rainfall, and inversely with sunshine duration or temperature. The effects of temperature and rainfall on DBP varied with latitude (P-interaction <0.02) and were greater in southern locations. Conclusion: BP varies with seasons and climate in different European areas and seasonality can be more important in southern locations. These changes in BP deserve attention as they may be responsible for a significant increase in cardiovascular risk which may be preventable.

  • 158.
    Dvorák, Martin
    et al.
    Masaryk University, Brno.
    Smrzova, Jana
    www.nefrologie.eu: Building an Electronic Source of Information on the Principles of Andragogy2010In: Alternativni metody vyuky 2010, Prague, 2010Conference paper (Refereed)
    Abstract [en]

    The cooperation between a patient and their physician represents a pre-requisite for successful treatment. Provided the patient is well-informed and willing to cooperate, their illness turns out to progress more slowly and, as a result, they usually live longer than the one who is not as they are more likely to take precautions against medical complications associated with it. Moreover, the quality of such a person’s life is higher and treatment less expensive.The nefrologie.eu portal aims to educate patients, their relatives and other people interested in the area of kidney diseases. Apart from the provision of information on how to prevent and alleviate kidney-related disorders, the portal conducts a perpetual needs analysis thereby ensuring it is the areas that interest patients most that are widely covered by it. In this respect, it also serves as a needs analysis tool for doctors to monitor the fields patients most frequently lack information about allowing them to pinpoint and focus on these during their sessions with their own patients.As the counseling section comprises answers to the questions (800 up to now) the visitors (more than 200 a day) have posted via the site and thus contains concrete information relevant to the individual visitors’ past, present and future lives, its educational impact is facilitated through the personalization factor. What also contributes to the efficiency of the educational process is the fact the information is presented through multiple presentation channels and thus ensures sufficient repetitions and variations on themes.The paper also discusses other principles of andragogy that appear crucial in building a publicly available electronic information source targeting medical education of adults.

  • 159.
    Dyrskjot, Lars
    et al.
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Reinert, Thomas
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Algaba, Ferran
    Univ Autonoma Barcelona, Sect Pathol, Fundacio Puigvert, Barcelona, Spain.
    Christensen, Emil
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Nieboer, Daan
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
    Hermann, Gregers G.
    Frederiksberg Univ Hosp, Dept Urol, Frederiksberg, Denmark.
    Mogensen, Karin
    Frederiksberg Univ Hosp, Dept Urol, Frederiksberg, Denmark.
    Beukers, Willemien
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
    Marquez, Mirari
    Spanish Natl Canc Res Ctr, Madrid, Spain.
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hoyer, Soren
    Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark.
    Ulhoi, Benedicte P.
    Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark.
    Hartmann, Arndt
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany.
    Stohr, Robert
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany.
    Wach, Sven
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany.
    Nawroth, Roman
    Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany.
    Schwamborn, Kristina
    Tech Univ Munich, Inst Pathol, Klinikum Rechts Isar, Munich, Germany.
    Tulic, Cane
    Univ Belgrade, Clin Ctr Serbia, Clin Urol, Fac Med, Belgrade, Serbia.
    Simic, Tatjana
    Univ Belgrade, Inst Med & Clin Biochem, Fac Med, Belgrade, Serbia.
    Junker, Kerstin
    Saarland Univ, Dept Urol, Homburg, Germany.
    Harving, Niels
    Aalborg Univ Hosp, Dept Urol, Aalborg, Denmark.
    Petersen, Astrid C.
    Aalborg Univ Hosp, Dept Pathol, Aalborg, Denmark.
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark.
    Keck, Bastian
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany.
    Grimm, Marc-Oliver
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany.
    Horstmann, Marcus
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany.
    Maurer, Tobias
    Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany.
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
    Real, Francisco X.
    Spanish Natl Canc Res Ctr, Madrid, Spain;Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
    Malats, Nuria
    Spanish Natl Canc Res Ctr, Madrid, Spain.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 3, p. 461-469Article in journal (Refereed)
    Abstract [en]

    Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

  • 160.
    Eckerbom, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Cox, Eleanor
    Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
    Buchanan, Charlotte
    Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Francis, Susan
    Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging2019In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 4, p. F693-F702Article in journal (Refereed)
    Abstract [en]

    Non-invasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 females, 13 males), Arterial Spin Labeling (ASL) to estimate regional renal perfusion, Blood Oxygen Level Dependent (BOLD) transverse relaxation rate (R2*) to estimate oxygenation, and Apparent Diffusion Coefficient (ADC), true diffusion (D) and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex, outer and inner medulla. Additionally, phase contrast (PC) MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index and renal volume. Similar patterns in all investigated parameters were observed in females and males. In conclusion, non-invasive MRI provides useful tools to evaluate intra renal differences in blood flow, perfusion, diffusion, oxygenation and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our current understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.

  • 161.
    Egevad, Lars
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Danneman, Daniela
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Drevin, Linda
    Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
    Correlation of Gleason Score in Biopsy and Radical Prostatectomy Specimens 2000-2012-A Registry Study of 15598 Men2015In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 95, p. 217A-218AArticle in journal (Other academic)
  • 162. Egevad, Lars
    et al.
    Kristiansen, Anna
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Prognostic Significance of Prostate Cancer with Seminal Vesicle Invasion on Radical Prostatectomy: A National Registry Study2017In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 97, p. 222A-222AArticle in journal (Refereed)
  • 163.
    Ejerblad, E.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fored, C. M.
    Karolinska Institutet, Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fryzek, J.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Dickman, P. W.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Elinder, C. G.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    McLaughlin, J. K.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Nyren, O.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Association between smoking and chronic renal failure in a nationwide population-based case-control study2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 8, p. 2178-2185Article in journal (Refereed)
    Abstract [en]

    For determining whether smoking is associated with an increased risk for chronic renal failure (CRF) overall and by type of renal disease, smoking data were analyzed from a nationwide population-based case-control study. Eligible as cases were native 18- to 74-yr-old Swedes whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women). A total of 926 cases (78% of all eligible) and 998 control subjects (75% of 1330 randomly selected subjects from the source population), frequency matched to the cases by gender and age within 10 yr, were included. A face-to-face interview and a self-administered questionnaire provided information about smoking habits and other lifestyle factors. Logistic regression models estimated odds ratios (OR) as measures of relative risk for disease-specific types of CRF among smokers compared with never-smokers. Despite a modest and nonsignificant overall association, the risk increased with high daily doses (OR among smokers of >20 cigarettes/d, 1.51; 95% confidence interval [CI], 1.06 to 2.15), long duration (OR among smokers for >40 yr, 1.45; 95% CI, 1.00 to 2.09), and a high cumulative dose (OR among smokers with >30 pack-years, 1.52; 95% CI, 1.08 to 2.14). Smoking increased risk most strongly for CRF classified as nephrosclerosis (OR among smokers with >20 pack-years, 2.2; 95% CI, 1.3 to 3.8), but significant positive associations were also noted with glomerulonephritis. This study thus suggests that heavy cigarette smoking increases the risk of CRF for both men and women, at least CRF classified as nephrosclerosis and glomerulonephritis.

  • 164.
    Ejerblad, E.
    et al.
    Department of Medical Epidemiology and Biostatistic Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Fored, C. M.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute and Karolinsak University Hospital, Stockholm, Sweden; Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Fryzek, J.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    McLaughlin, J. K.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Nyren, O.
    Department of Medical Epidemiology and Biostatistic Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Obesity and risk for chronic renal failure2006In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 17, no 6, p. 1695-1702Article in journal (Refereed)
    Abstract [en]

    Few large-scale epidemiologic studies have quantified the possible link between obesity and chronic renal failure (CRF). This study analyzed anthropometric data from a nationwide, population-based, case-control study of incident, moderately severe CRF. Eligible as cases were all native Swedes who were aged 18 to 74 yr and had CRF and whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women) during the study period. A total of 926 case patients and 998 control subjects, randomly drawn from the study base, were enrolled. Face-to-face interviews, supplemented with self-administered questionnaires, provided information about anthropometric measures and other lifestyle factors. Logistic regression models with adjustments for several co-factors estimated the relative risk for CRF in relation to body mass index (BMI). Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three-fold excess risk for CRF, relative to BMI<25. Obesity (BMI>or=30) among men and morbid obesity (BMI>or=35) among women anytime during lifetime was linked to three- to four-fold increases in risk. The strongest association was with diabetic nephropathy, but two- to three-fold risk elevations were observed for all major subtypes of CRF. Analyses that were confined to strata without hypertension or diabetes revealed a three-fold increased risk among patients who were overweight at age 20, whereas the two-fold observed risk elevation among those who had a highest lifetime BMI of >35 was statistically nonsignificant. Obesity seems to be an important-and potentially preventable-risk factor for CRF. Although hypertension and type 2 diabetes are important mediators, additional pathways also may exist.

  • 165.
    Ekdahl, Kristina N
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Cardiovascular disease in haemodialysis: role of the intravascular innate immune system.2017In: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 13, no 5, p. 285-296Article, review/survey (Refereed)
    Abstract [en]

    Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.

  • 166.
    Eliasson, Mona
    et al.
    Halmstad University, School of Social and Health Sciences (HOS).
    Karlsson, Erika
    Halmstad University, School of Social and Health Sciences (HOS).
    Mannens ensak eller bådas angelägenhet: Prostatacancers påverkan på den heterosexuella relationen2009Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    When a man is diagnosed with prostate cancer it implies a psychological strain for the man and his female partner where reactions such as shock, loss of meaning, loneliness and anxiety are common. The purpose of this literature review was to describe how everyday life is perceived and influenced in couples where the man has been diagnosed with prostate cancer. The results of the study are based on ten scientific articles focused on exploring couple’s experiences of the disease and how they are affected by the situation. Symptoms such as impotence, incontinence and fatigue were changes that affected the couple’s everyday life and their relationship. These changes were psychologically trying for the couple’s health and their quality of life decreased because of the cancer.  Psychological problems like depression, anxiety and guilt were more common for the woman. Despite the fact that the couples were in great need of information, they felt that health care providers were not attentive to these needs. Clearer guidelines are needed within the health-care system for how couples living with prostate cancer should be treated. The nurse would thereafter be better equipped to meet the couple’s needs for information and support. The nurse should highlight and approach women’s individual needs and show openness towards the sexual problems that can befall couples. More research is needed, particularly in Scandinavia, in order to get a clearer picture of how a homosexual and heterosexual relationship is affected by prostate cancer.

  • 167.
    Eriksson, Daniel
    et al.
    Quantify Research, Stockholm, Sweden.
    Karlsson, Linda
    Quantify Research, Stockholm, Sweden.
    Eklund, Oskar
    Quantify Research, Stockholm, Sweden.
    Dieperink, Hans
    Department of Nephrology, Odense University Hospital, Odense C, Denmark.
    Honkanen, Eero
    Division of Nephrology, Department of Medicine , Helsinki University Central Hospital, Helsinki, Finland.
    Melin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Selvig, Kristian
    Department of Nephrology, Vestre Viken Hospital Trust, Drammen, Norway.
    Lundberg, Johan
    Otsuka Pharma Scandinavia, Stockholm, Sweden.
    Health-related quality of life across all stages of autosomal dominant polycystic kidney disease2017In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 32, no 12, p. 2106-2111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease.

    METHODS: A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients.

    RESULTS: Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5.

    CONCLUSIONS: Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered.

  • 168.
    Erlandsson, Ann
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden; Department of Environmental and Life Sciences/Biology, Karlstad University, Karlstad, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Sven-Olof
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Vyas, Chraig
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    Wikström, Pernilla
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 129-133Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa.

    MATERIALS AND METHODS: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category.

    RESULTS: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97).

    CONCLUSION: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.

  • 169. Erlandsson, Ann
    et al.
    Carlsson, Jessica
    Andersson, Sven-Olof
    Vyas, Chraig
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andrén, Ove
    Davidsson, Sabina
    Rider, Jennifer R.
    High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 129-133Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa. Materials and methods: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category. Results: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97). Conclusion: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.

  • 170.
    Erlandsson, Ann
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology.
    Lundholm, Marie
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Fält, Anna
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Sven-Olof
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    M2 macrophages and regulatory T cells in lethal prostate cancer2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 4, p. 363-369Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs.

    METHODS: were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.

    RESULTS: showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.

    CONCLUSIONS: Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs , promote an immunosuppressive environment.

  • 171.
    Evans, Marc
    et al.
    Llandough Hosp, Diabet Resource Ctr, Cardiff, S Glam, Wales.
    Palaka, Eirini
    AstraZeneca, Global Hlth Econ, Cambridge, England.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Bennett, Hayley
    Hlth Econ & Outcomes Res Ltd, Cardiff, S Glam, Wales.
    Linde, Cecilia
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Qin, Lei
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    McEwan, Phil
    Hlth Econ & Outcomes Res Ltd, Cardiff, S Glam, Wales;Swansea Univ, Sch Human & Hlth Sci, Swansea, W Glam, Wales.
    Bakhai, Ameet
    Royal Free Hosp, Dept Cardiol, London, England.
    The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease2019In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 20, article id 31Article in journal (Refereed)
    Abstract [en]

    Background

    People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD.

    Methods

    A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses.

    Results

    Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia.

    Conclusion

    This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

  • 172. Fall, Katja
    et al.
    Strömberg, Fredrik
    Rosell, Johan
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Varenhorst, Eberhard
    Reliability of death certificates in prostate cancer patients2008In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, no 4, p. 352-357Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the reliability of cause-of-death diagnoses among prostate cancer patients. MATERIAL AND METHODS: Information from death certificates obtained from the Swedish Death Register was compared with systematically reviewed medical records from the population-based Swedish Regional Prostate Cancer Register, South-East Region. In total, 5675 patients were included who had been diagnosed with prostate cancer between 1987 and 1999 and who had died before 1 January 2003. RESULTS: The proportion of prostate cancer cases classified as having died from prostate cancer was 3% higher in the official death certificates than in the reviewed records [0.03, 95% confidence interval (CI) 0.02 to 0.04]. Overall agreement between the official cause of death and the reviewed data was 86% (95% CI 85 to 87%). A higher accuracy was observed among men with localized disease (88%, 95% CI 87 to 89%), aged 60 years or younger at death (96%, 95% CI 93 to 100%), or who had undergone curative treatment (91%, 95% CI 88 to 95%). This study indicates a relatively high reliability of official cause-of-death statistics of prostate cancer patients in Sweden. CONCLUSION: Mortality data obtained from death certificates may be useful in the evaluation of large-scale prostate cancer intervention programmes, especially among younger patients with localized disease.

  • 173.
    Feldreich, Tobias
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Nowak, Christoph
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Solna, Sweden.
    Ripsweden, Jonas
    Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Campus Flemingsberg, Stockholm, Sweden.
    Qureshi, Abdul Rashid
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Heimburger, Olof
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Barany, Peter
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Stenvinkel, Peter
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Vuilleumier, Nicolas
    Geneva Univ Hosp, Dept Genet Lab Med & Pathol, Geneva, Switzerland;Geneva Fac Med, Dept Med Specialties, Geneva, Switzerland.
    Kalra, Philip A.
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England;Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England.
    Green, Darren
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England;Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England.
    Arnlov, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease2019In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 32, no 1, p. 111-119Article in journal (Refereed)
    Abstract [en]

    Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n=183, 55% women, mean age 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n=186, 73% women, mean age 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).

    Results

    In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p=0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C=0.777 to C=0.799 and C=0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p=0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.

    Conclusions

    Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

  • 174.
    Fellström , Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zannad, Faiez
    Schmieder, Roland
    Holdaas, Hallvard
    Jardine, Alan
    Rose, Helen
    Wilpshaar, Wim
    Effect of rosuvastatin on outcomes in chronic haemodialysis patients: design and rationale of the AURORA study2005In: Current controlled trials. Cardiovascular medicine (Online), ISSN 1468-6708, E-ISSN 1468-6694, Vol. 6, no 1, p. 9-16Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis. METHODS: More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event. CONCLUSION: Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.

  • 175.
    Fellström , Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan G.
    Scmieder, R.E.
    Holdaas, H.
    Bannister, K.
    Beutler, J.
    Chae, D.W.
    Chevalie, A.
    Cobbe, S.M.
    Grönhagen-Riska, C.
    De Lima, J.J.
    Lins, R.
    Mayer, G.
    McMahon, A.W.
    Parving, H.H.
    Remuzzi, G.
    Samuelsson, O.
    Sonkodi, S.
    Sci, D.
    Süleymanlar, G.
    Tsakiris, D.
    Tesar, V.
    Todorov, V.
    Wiecek, A.
    Wüthrich, R.P.
    Gottlow, M.
    Johnsson, E.
    Zannard, F.
    Rosuvastatin and Cardiovascuular Events in Patients Undergoing Hemodialysis2009In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 360, no 14, p. 1395-1407Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

  • 176.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Effects of lowering LDL-cholesterol with ezetimible/simvastatin in patients with advanced chronic kidney disease: the Study  of Heart and Renal protectionManuscript (preprint) (Other academic)
  • 177.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Lack of effect lowering LDL cholesterol on cancer risk: metaanalysis of individual data from 175,000 participants in 27 randomized trials on statin therapy.Manuscript (preprint) (Other academic)
  • 178.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Risk Factors and Management Options for Cardiovascular Disease (CVD) in Kidney Transplantation2013In: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, no 2, p. S15-S16Article in journal (Refereed)
  • 179.
    Fellström, Bengt C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Barratt, Jonathan
    Univ Leicester, Leicester, Leics, England..
    Cook, Heather
    PharmaL Consulting AB, Stockholm, Sweden..
    Coppo, Rosanna
    Regina Margherita Hosp, Fdn Ric Molinette, Turin, Italy..
    Feehally, John
    Univ Leicester, Leicester, Leics, England..
    de Fijter, Johan W.
    Leiden Univ, Med Ctr, Leiden, Netherlands..
    Floege, Jürgen
    Rhein Westfal TH Aachen, Aachen, Germany..
    Hetzel, Gerd
    HeinrichHeine Univ, DaVita Renal Ctr, Dusseldorf, Germany..
    Jardine, Alan G.
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Locatelli, Francesco
    Osped A Manzoni, Lecce, Italy..
    Maes, Bart D.
    AZ Delta, Roeselare, Belgium..
    Mercer, Alex
    Pharmalink AB, Stockholm, Sweden..
    Ortiz, Fernanda
    Helsinki Univ Hosp, Helsinki, Finland..
    Praga, Manuel
    Univ Complutense Madrid, Investigat Inst Hosp Octubre 12, Madrid, Spain..
    Sorensen, Soren S.
    Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark..
    Tesar, Vladimir
    Charles Univ Prague, Prague, Czech Republic..
    Del Vecchio, Lucia
    Osped A Manzoni, Lecce, Italy..
    Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 389, no 10084, p. 2117-2127Article in journal (Refereed)
    Abstract [en]

    Background: IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy.

    Methods: We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries. We recruited patients aged at least 18 years with biopsy-confirmed primary IgA nephropathy and persistent proteinuria despite optimised renin-angiotensin system (RAS) blockade. We randomly allocated patients with a computer algorithm, with a fixed block size of three, in a 1:1:1 ratio to 16 mg/day TRF-budesonide, 8 mg/day TRF-budesonide, or placebo, stratified by baseline urine protein creatinine ratio (UPCR). Patients self-administered masked capsules, once daily, 1 h before breakfast during the treatment phase. All patients continued optimised RAS blockade treatment throughout the trial. Our primary outcome was mean change from baseline in UPCR for the 9-month treatment phase, which was assessed in the full analysis set, defined as all randomised patients who took at least one dose of trial medication and had at least one post-dose efficacy measurement. Safety was assessed in all patients who received the intervention. This trial is registered with ClinicalTrials.gov, number NCT01738035.

    Findings: Between Dec 11, 2012, and June 25, 2015, 150 randomised patients were treated (safety set) and 149 patients were eligible for the full analysis set. Overall, at 9 months TRF-budesonide (16 mg/day plus 8 mg/day) was associated with a 24.4% (SEM 7.7%) decrease from baseline in mean UPCR (change in UPCR vs placebo 0.74; 95% CI 0.59-0.94; p=0.0066). At 9 months, mean UPCR had decreased by 27.3% in 48 patients who received 16 mg/day (0.71; 0.53-0.94; p=0.0092) and 21.5% in the 51 patients who received 8 mg/day (0.76; 0.58-1.01; p=0.0290); 50 patients who received placebo had an increase in mean UPCR of 2.7%. The effect was sustained throughout followup. Incidence of adverse events was similar in all groups (43 [88%] of 49 in the TRF-budesonide 16 mg/day group, 48 [94%] of 51 in the TRF-budesonide 8 mg/day, and 42 [84%] of 50 controls). Two of 13 serious adverse events were possibly associated with TRF-budesonide-deep vein thrombosis (16 mg/day) and unexplained deterioration in renal function in follow-up (patients were tapered from 16 mg/day to 8 mg/day over 2 weeks and follow-up was assessed 4 weeks later).

    Interpretation: TRF-budesonide 16 mg/day, added to optimised RAS blockade, reduced proteinuria in patients with IgA nephropathy. This effect is indicative of a reduced risk of future progression to end-stage renal disease. TRF-budesonide could become the first specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation.

  • 180.
    Fellström, Bengt C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Holdaas, Hallvard
    Chronic allograft nepropathy2009In: Evidence-based nephrology / [ed] Donald A. Molony, Jonathan C. Craig, Oxford: Wiley-Blackwell , 2009, , p. 1-9p. 599-608Chapter in book (Other academic)
  • 181.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Holdaas, Hallvard
    Jardine, Alan
    Cardiovascular risk in renal transplantation2008In: Trends in Transplantation, ISSN 1887-455X, Vol. 2, no 2, p. 92-100Article, book review (Other academic)
    Abstract [en]

    Renal transplant patients suffer from a higher risk of cardiovascular morbidity and mortality. The risk-factor spectrum is different from the general population; several risk factors are transplantation specific, and to a large extent dependent on the immunosuppressive drugs used to prevent rejection. Due to the complexity of the risk factors, the variable impact of each factor on different cardiovascular outcomes and the inter-relationships between risk factors, it is difficult to judge the overall cardiovascular risk in a single renal transplant patient. In this paper we review risk-factor data from the literature, limited to single risk factors and their impact on single cardiovascular outcomes. We believe that a cardiovascular risk calculator specific to the renal transplant population, which takes into account all the important risk factors for a cardiovascular event, based upon a high quality database such as the ALERT data set, may provide a solid guidance to means to assess the overall cardiovascular risk in renal transplant recipients.

  • 182.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Holdaas, Hallvard
    Jardine, Alan G.
    Nyberg, Gudrun
    Grönhagen-Riska, Carola
    Madsen, Soren
    Neumayer, Hans-Hellmut
    Cole, Edward
    Maes, Bart
    Ambühl, Patrice
    Olsson, Anders G.
    Staffler, Beatrix
    Pedersen, Terje R.
    Risk factors for reaching renal endpoints in the assessment of Lescol in renal transplantation (ALERT) trial2005In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 79, no 2, p. 205-212Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the study was to identity risk factors for long-term renal transplant function and development of chronic allograft nephropathy (CAN) in renal transplant recipients included in the Assessment of Lescol in Renal Transplantation (ALERT) trial. METHODS: The ALERT trial was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 and 80 mg/day, in renal transplant recipients who were randomized to receive fluvastatin (Lescol) (n = 1,050) or placebo (n = 1,052) over 5 to 6 years of follow-up. Renal endpoints including graft loss or doubling of serum creatinine or death were analyzed by univariate and multivariate regression analysis in the placebo group. RESULTS: There were 137 graft losses (13.5%) in the placebo group, mainly caused by CAN (82%). Univariate risk factors for graft loss or doubling of serum creatinine were as follows: serum creatinine, proteinuria, hypertension, pulse pressure, time since transplantation, donor age, human leukocyte antigen-DR mismatches, treatment for rejection, low high-density lipoprotein cholesterol, and smoking. Multivariate analysis revealed independent risk factors for graft loss as follows: serum creatinine (relative risk [RR], 3.12 per 100-microM increase), proteinuria (RR, 1.64 per 1-g/24 hr increase), and pulse pressure (RR, 1.12 per 10 mm Hg), whereas age was a protective factor. With patient death in the composite endpoint, diabetes mellitus, smoking, age, and number of transplantations were also risk factors. CONCLUSIONS: Independent risk factors for graft loss or doubling of serum creatinine or patient death are mainly related to renal transplant function, proteinuria, and blood pressure, which emphasizes the importance of renoprotective treatment regimens in this population.

  • 183.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Holdaas, Halvard
    Jardine, Alan
    Schmieder, Roland
    Gottlow, Mattis
    Eva, Jonsson
    Zannad, Faiez
    Cardiovascular benefits and improved patient survival by rosuvastatin treatment in hemodialyis patients are determined by normalization of CRP and LDL-cholesterol - A prospective analyis of the AURORA trial.Manuscript (preprint) (Other academic)
  • 184.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Holdaas, Halvard
    Jardine, Alan
    Tiran, Beate
    Weihrauch, Gisela
    Maerz, Winfried
    Calcium, Phosphate, Parathyroid Hormone and Osteoprotegerin as Risk Factors for Cardiovascular disease and Graft Loss in Renal TransplantationManuscript (preprint) (Other academic)
  • 185.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan G.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cole, E.
    Neumayer, Hans-Helmutt
    Maes, Bart
    Gimpelewicz, Claudio
    Holdaas, Hallvard
    Renal dysfunction is a strong and independent risk factor for mortality and cardiovascular complications in renal transplantation2005In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 5, no 8, p. 1986-1991Article in journal (Refereed)
    Abstract [en]

    Renal transplant recipients (RTR) have shortened life expectancy, primarily due to premature cardiovascular disease (CVD). Traditional CVD risk factors are highly prevalent. In addition, several non-traditional risk factors may contribute to the high risk. The aim of the study was to evaluate the effects of renal dysfunction on mortality and cardiovascular complications in 1052 placebo-treated patients of the Assessment of LEscol in Renal Transplantation (ALERT) trial. Follow-up was 5-6 years and endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke. The effects of serum creatinine at baseline on these endpoints were evaluated. Elevated serum creatinine in RTR was a strong and independent risk factor for MACE, cardiac, non-cardiovascular, and all-cause mortality, but not for stroke or non-fatal MI alone. Serum creatinine was associated with increased mortality and MACE, independent of established CVD risk factors. Graft loss resulted in increased incidences of non-cardiovascular death, all-cause mortality, MACE and non-fatal MI. In conclusion, elevated serum creatinine is a strong risk factor for all-cause, non-cardiovascular and cardiac mortality, and MACE, independent of traditional risk factors, but not for stroke or non-fatal MI alone.

  • 186.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan G.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cole, Edward
    Grönhagen-Riska, Carola
    Neumayer, Hans H.
    Maes, Bart
    Gimpelewicz, Claudio
    Holdaas, Hallvard
    Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation: experience from the Assessment of Lescol in Renal Transplantation trial2005In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 79, no 9, p. 1160-1163Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients. In renal-transplant recipients, immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors. Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different populations. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial. METHODS: All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy. Follow-up was 5 to 6 years, and endpoints included cardiac death, noncardiovascular death, all-cause mortality, major adverse cardiac event (MACE), stroke, nonfatal myocardial infarction, and graft loss. RESULTS: Baseline serum creatinine was strongly and independently associated with increased cardiac, noncardiovascular, and all-cause mortality, as well as MACE and graft loss. Serum creatinine was not a risk factor for stroke or nonfatal myocardial infarction. CONCLUSIONS: Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause, noncardiovascular and cardiac mortality, MACE, and graft loss.

  • 187.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mensur,
    Mansour,
    Larsson,
    Söderberg-Naucler,
    CMV reactivity in renal tranplants with CANManuscript (preprint) (Other academic)
  • 188.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Bra lärobok – kan bli bättre2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 763Article, book review (Other academic)
  • 189.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Nu finns en ny svensk lärobok i njurmedicin2016In: Vaskulär Medicin, Vol. 32, no 41Article, book review (Other academic)
  • 190.
    Fernström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Hylander Rössner, Britta
    Njurmedicinska kliniken, Karolinska universitetssjukhuset, Solna .
    Polycystisk njursjukdom (ADPKD)2015Other (Other academic)
    Abstract [sv]
    • Polycystisk njursjukdom (ADPKD) innebär att man i njurarna bildar ett fåtal till hundratals cystor i njurarna som slår ut den normala njurfunktionen och ökar buktrycket.
    • Orsakas av mutationer på PKD-1 och PKD-2-generna.
    • Ärvs autosomalt dominant.
    • Vanliga symtom är:- Tryckkänsla/smärta i buken- Njursten- Nedsatt urinkoncentrationsförmåga- Hypertoni- UVI- Hematuri- Uremiska symtom
    • Kan ge manifestationer extrarenalt- Levercystor- Pankreascystor- Intracerebrala aneurysm- Klaffvitium- Divertikulos- Bukväggsbråck
    • Diagnos sätts antingen på förekomst av cystor och ärftlighet för ADPKD eller enbart på förekomst av cystor (dock krävs då fler cystor).
    • Botande behandling annan än transplantation saknas.
    • Symtomlindrande behandling syftar till att minska mortalitet och morbiditet på grund av sjunkande njurfunktion.
    • Transplantation är indicerat om patienten är uremisk.
    • Nya behandlingar är under utveckling.
  • 191. Fernández-Pello, Sergio
    et al.
    Hofmann, Fabian
    Tahbaz, Rana
    Marconi, Lorenzo
    Lam, Thomas B
    Albiges, Laurence
    Bensalah, Karim
    Canfield, Steven E
    Dabestani, Saeed
    Giles, Rachel H
    Hora, Milan
    Kuczyk, Markus A
    Merseburger, Axel S
    Powles, Thomas
    Staehler, Michael
    Volpe, Alessandro
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bex, Axel
    A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma.2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, no 3, p. 426-436Article, review/survey (Refereed)
    Abstract [en]

    CONTEXT: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown.

    OBJECTIVE: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC.

    EVIDENCE ACQUISITION: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken.

    EVIDENCE SYNTHESIS: The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03-1.92 and 1.41, 95% CI: 0.88-2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67-2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9-2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91-1.86). Sunitinib was associated with more Grade 3-4 adverse events than everolimus, although this was not statistically significant.

    CONCLUSIONS: This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed.

    PATIENT SUMMARY: We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.

  • 192.
    Ferry, Sven
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Urinary tract infections in primary health care in northern Sweden: epidemiological, bacteriological and clinical aspects1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The epidemiology of urinary tract infection (UTI) in the population of Vännäs (8 000 inhabitants) was studied during one year. The annual incidence increased from 0.5% in the first decade of life to more than 10% in the age group 90-100 years. Male UTI comprised only 13% of the episodes, increased after middle age and contributed 4 0% by > 80 years of age. At 17 PHC centres (PHCCs) a prevalence study (McPHC) of mainly uncomplicated UTI was performed. Most episodes were acutely symptomatic (lower 75%, upper 5%).

    Microscopy of wet-stained urinary sediment with a minimum of moderate amount of bacteria and/or 5 leukocytes per high power field (4 00 x) as breakpoint resulted in a desired high sensitivity (97%) and 86% efficacy in acutely symptomatic patients. Diagnosis of bacteriuria using Uricult dipslides yielded acceptable results with an overall efficacy of 88%. Nitrite test and Uriglox showed an unacceptable low mean sensitivity ofR56 and 69%, respectively. A positive nitrite, sediment or Uricult , when used in combination, was optimal in diagnosing UTI with a sensitivity of 98% in acutely symptomatic patients during their office visits.

    The average risk of drug resistance was 17% in the Vännäs study. Sensicult satisfactorily predicted drug sensitivity (93%) but not bacterial drug resistance (50%). Using Uricult with classification of bacteriuria by Gram-grouping, lactose and catalase reactions for targeting UTI therapy, according to local guidelines, resulted in a similar low risk (6 %) of prescribing drugs to which the organisms were resistagt as when using Sensicult (7%). This development of the Uricult method is simple and can be recommended for office practice in PHC.

    The spectrum of bacteria causing UTI and their drug resistance was more associated with the selection of patients, sex and age than with symptoms. The pattern of drug resistance was little influenced by UTI history and the mean pretherapy resistance for the seven drugs tested in McPHC was low (7%). Drug resistance was increased in failure (mean 24%) but not in early or repeated recurrence. In McPHC therapy resulted in 8% bacteriological failure and 12% early recurrence, irrespective of whether the bacteria were classified as sensitive or resistant in vitro to the drug given. Thus, in order to be of prognostic value for therapy of uncomplicated UTI, high-level breakpoints focusing more on peak urinary drug concentrations need to be studied.

    UTI symptoms in McPHC were eradicated in only 2/3 of the bacterio- logically cured episodes and in 1/3 of the failures at control 1-3 days posttherapy showing that symptoms are an unreliable indicator of UTI.

    From current literature, it seems unlikely that asymptomatic bacteriuria (ABU) plays a major role in the development of uremia due to chronic pyelonephritis. With the exception of ABU in pregnancy, therapy seems to yield no benefit. Omitting posttherapy bacteriuria controls in patients with symptoms eradicated, at least in women with uncomplicated UTI, would lead to considerable savings both for patients and the health care system.

  • 193. Figueroa, Jonine D.
    et al.
    Han, Summer S.
    Garcia-Closas, Montserrat
    Baris, Dalsu
    Jacobs, Eric J.
    Kogevinas, Manolis
    Schwenn, Molly
    Malats, Nuria
    Johnson, Alison
    Purdue, Mark P.
    Caporaso, Neil
    Landi, Maria Teresa
    Prokunina-Olsson, Ludmila
    Wang, Zhaoming
    Hutchinson, Amy
    Burdette, Laurie
    Wheeler, William
    Vineis, Paolo
    Siddiq, Afshan
    Cortessis, Victoria K.
    Kooperberg, Charles
    Cussenot, Olivier
    Benhamou, Simone
    Prescott, Jennifer
    Porru, Stefano
    Bueno-de-Mesquita, H. Bas
    Trichopoulos, Dimitrios
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Clavel-Chapelon, Françoise
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth
    Tjønneland, Anne
    Brenan, Paul
    Chang-Claude, Jenny
    Riboli, Elio
    Conti, David
    Gago-Dominguez, Manuela
    Stern, Mariana C.
    Pike, Malcolm C.
    Van den Berg, David
    Yuan, Jian-Min
    Hohensee, Chancellor
    Rodabough, Rebecca
    Cancel-Tassin, Geraldine
    Roupret, Morgan
    Comperat, Eva
    Chen, Constance
    De Vivo, Immaculata
    Giovannucci, Edward
    Hunter, David J.
    Kraft, Peter
    Lindstrom, Sara
    Carta, Angela
    Pavanello, Sofia
    Arici, Cecilia
    Mastrangelo, Giuseppe
    Karagas, Margaret R.
    Schned, Alan
    Armenti, Karla R.
    Hosain, G. M. Monawar
    Haiman, Chris A.
    Fraumeni, Joseph F., Jr.
    Chanock, Stephen J.
    Chatterjee, Nilanjan
    Rothman, Nathaniel
    Silverman, Debra T.
    Genome-wide interaction study of smoking and bladder cancer risk2014In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 35, no 8, p. 1737-1744Article in journal (Refereed)
    Abstract [en]

    Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 x 10(-5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 x 10(-7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 x 10-7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.

  • 194. Figueroa, Jonine D.
    et al.
    Middlebrooks, Candace D.
    Banday, A. Rouf
    Ye, Yuanqing
    Garcia-Closas, Montserrat
    Chatterjee, Nilanjan
    Koutros, Stella
    Kiemeney, Lambertus A.
    Rafnar, Thorunn
    Bishop, Timothy
    Furberg, Helena
    Matullo, Giuseppe
    Golka, Klaus
    Gago-Dominguez, Manuela
    Taylor, Jack A.
    Fletcher, Tony
    Siddiq, Afshan
    Cortessis, Victoria K.
    Kooperberg, Charles
    Cussenot, Olivier
    Benhamou, Simone
    Prescott, Jennifer
    Porru, Stefano
    Dinney, Colin P.
    Malats, Nuria
    Baris, Dalsu
    Purdue, Mark P.
    Jacobs, Eric J.
    Albanes, Demetrius
    Wang, Zhaoming
    Chung, Charles C.
    Vermeulen, Sita H.
    Aben, Katja K.
    Galesloot, Tessel E.
    Thorleifsson, Gudmar
    Sulem, Patrick
    Stefansson, Kari
    Kiltie, Anne E.
    Harland, Mark
    Teo, Mark
    Offit, Kenneth
    Vijai, Joseph
    Bajorin, Dean
    Kopp, Ryan
    Fiorito, Giovanni
    Guarrera, Simonetta
    Sacerdote, Carlotta
    Selinski, Silvia
    Hengstler, Jan G.
    Gerullis, Holger
    Ovsiannikov, Daniel
    Blaszkewicz, Meinolf
    Esteban Castelao, Jose
    Calaza, Manuel
    Martinez, Maria Elena
    Cordeiro, Patricia
    Xu, Zongli
    Panduri, Vijayalakshmi
    Kumar, Rajiv
    Gurzau, Eugene
    Koppova, Kvetoslava
    Bueno-De-Mesquita, H. Bas
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Clavel-Chapelon, Francoise
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth C.
    Tjonneland, Anne
    Brennan, Paul
    Chang-Claude, Jenny
    Riboli, Elio
    Conti, David
    Stern, Marianna C.
    Pike, Malcolm C.
    Van den Berg, David
    Yuan, Jian-Min
    Hohensee, Chancellor
    Jeppson, Rebecca P.
    Cancel-Tassin, Geraldine
    Roupret, Morgan
    Comperat, Eva
    Turman, Constance
    De Vivo, Immaculata
    Giovannucci, Edward
    Hunter, David J.
    Kraft, Peter
    Lindstrom, Sara
    Carta, Angela
    Pavanello, Sofia
    Arici, Cecilia
    Mastrangelo, Giuseppe
    Kamat, Ashish M.
    Zhang, Liren
    Gong, Yilei
    Pu, Xia
    Hutchinson, Amy
    Burdett, Laurie
    Wheeler, William A.
    Karagas, Margaret R.
    Johnson, Alison
    Schned, Alan
    Hosain, G. M. Monawar
    Schwenn, Molly
    Kogevinas, Manolis
    Tardon, Adonina
    Serra, Consol
    Carrato, Alfredo
    Garcia-Closas, Reina
    Lloreta, Josep
    Andriole, Gerald, Jr.
    Grubb, Robert, III
    Black, Amanda
    Diver, W. Ryan
    Gapstur, Susan M.
    Weinstein, Stephanie
    Virtamo, Jarmo
    Haiman, Christopher A.
    Landi, Maria Teresa
    Caporaso, Neil E.
    Fraumeni, Joseph F., Jr.
    Vineis, Paolo
    Wu, Xifeng
    Chanock, Stephen J.
    Silverman, Debra T.
    Prokunina-Olsson, Ludmila
    Rothman, Nathaniel
    Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry2016In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 6, p. 1203-1214Article in journal (Refereed)
    Abstract [en]

    Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

  • 195.
    Fored, C. M.
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Ejerblad, E.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Fryzek, J. P.
    The International Epidemiology Institute, Rockville, MD, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
    Lambe, M.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Elinder, C. G.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Socio-economic status and chronic renal failure: a population-based case-control study in Sweden2003In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 18, no 1, p. 82-88Article in journal (Refereed)
    Abstract [en]

    Background: Low socio-economic status is associated with the occurrence of several different chronic diseases, but evidence regarding renal disease is scant. To explore whether the risk of chronic renal failure varies by socio-economic status, we performed a population-based case-control study in Sweden.

    Methods: All native residents from May 1996 to May 1998, aged 18-74 years, formed the source population. Cases (n = 926) were incident patients with chronic renal failure in a pre-uraemic stage. Control subjects (n = 998) were randomly selected within the source population. Exposures were assessed at personal interviews and relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for age, sex, body mass index (BMI), smoking, alcohol consumption and regular analgesics use.

    Results: In families with unskilled workers only, the risk of chronic renal failure was increased by 110% [OR = 2.1; 95% confidence interval (CI), 1.1-4.0] and 60% (OR = 1.6; 95% CI, 1.0-2.6) among women and men, respectively, relative to subjects living in families in which at least one member was a professional. Subjects with 9 years or less of schooling had a 30% (OR = 1.3; 95% CI, 1.0-1.7) higher risk compared with those with a university education. The excess risk was of similar magnitude regardless of underlying renal disease.

    Conclusions: Low socio-economic status is associated with an increased risk of chronic renal failure. The moderate excess was not explained by age, sex, BMI, smoking, alcohol or analgesic intake. Thus, socio-economic status appears to be an independent risk indicator for chronic renal failure in Sweden.

  • 196.
    Fored, C. M.
    et al.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Ejerblad, E.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Fryzek, J. P.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Dickman, P. W.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Signorello, L. B.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Lipworth, L.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Elinder, C. G.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Blot, W. J.
    International Epidemiology Institute, Rockville, MD, United States.
    McLaughlin, J. K.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Zack, M. M.
    National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, United States .
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Acetaminophen, aspirin, and chronic renal failure2001In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 345, no 25, p. 1801-1808Article in journal (Refereed)
    Abstract [en]

    Background: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect.

    Methods: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics.

    Results: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated.

    Conclusions: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

  • 197.
    Fored, C. M.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden.
    Nise, G.
    Division of Occupational Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden.
    Ejerblad, E.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Fryzek, J. P.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    McLaughlin, J. K.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Elinder, C. G.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden.
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Absence of association between organic solvent exposure and risk of chronic renal failure: a nationwide population-based case-control study2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 1, p. 180-186Article in journal (Refereed)
    Abstract [en]

    Exposure to organic solvents has been suggested to cause or exacerbate renal disease, but methodologic concerns regarding previous studies preclude firm conclusions. We examined the role of organic solvents in a population-based case-control study of early-stage chronic renal failure (CRF). All native Swedish residents aged 18 to 74 yr, living in Sweden between May 1996 and May 1998, formed the source population. Incident cases of CRF in a pre-uremic stage (n = 926) and control subjects (n = 998), randomly selected from the study base, underwent personal interviews that included a detailed occupational history. Expert rating by a certified occupational hygienist was used to assess organic solvent exposure intensity and duration. Relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for potentially important covariates. The overall risk for CRF among subjects ever exposed to organic solvents was virtually identical to that among never-exposed (OR, 1.01; 95% confidence interval [CI], 0.81 to 1.25). No dose-response relationships were observed for lifetime cumulative solvent exposure, average dose, or exposure frequency or duration. The absence of association pertained to all subgroups of CRF: glomerulonephritis (OR, 0.96; 95% CI, 0.68 to 1.34), diabetic nephropathy (OR, 1.02; 95% CI, 0.74 to 1.41), renal vascular disease (OR, 1.16; 95% CI, 0.76 to 1.75), and other renal CRF (OR, 0.92; 95% CI, 0.66 to 1.27). The results from a nationwide, population-based study do not support the hypothesis of an adverse effect of organic solvents on CRF development, in general. Detrimental effects from subclasses of solvents or on specific renal diseases cannot be ruled out.

  • 198.
    Forsberg, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Medicin-geriatriska kliniken, Skellefteå lasarett.
    Jonsson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Christofer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Microemboli, developed during haemodialysis, pass the lung barrier and may cause ischaemic lesions in organs such as the brain2010In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 25, no 8, p. 2691-2695Article in journal (Refereed)
    Abstract [en]

    The infused and returning fluid from HD devices contains air microbubbles that enter the patient without triggering any alarms. These small emboli pass the lung and may cause ischaemic lesions in organs supported by the arterial circuit, such as the brain.

  • 199.
    Forsman, Ramona
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Common blood markers as possible predictors of response to neoadjuvant chemotherapy, in muscle-invasive urinary bladder cancer2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 200. Fossa, Sophie D.
    et al.
    Wiklund, Fredrik
    Klepp, Olbjorn
    Angelsen, Anders
    Solberg, Arne
    Dumber, Jan-Erik
    Hoyer, Morten
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results of The Scandinavian Prostate Cancer Group-72016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 4, p. 684-691Article in journal (Refereed)
    Abstract [en]

    Background: In high-risk prostate cancer (PCa), no study with observation times beyond 10 yr has demonstrated survival improvement after addition of prostatic radiotherapy (RAD) to endocrine treatment (ET) alone. Objective: To compare mortality rates in patients receiving ET alone versus ET + RAD. Design, settings, and participants: From 1996 to 2002, 875 Scandinavian patients with high-risk (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian Prostate Cancer Group-7). After 3 mo with total androgen blockade in all patients, all individuals continued lifelong antiandrogen monotherapy. Those randomized to ET + RAD started prostate radiotherapy (70 Gy) at 3 mo. Outcome, measurements and statistical analysis: PCa-specific 15-yr mortality represented the primary endpoint. Assessment of the combination treatment effect and prognostic factors was performed in competing risk analyses and Cox proportional-hazard models. Intervention: RAD added to ET. Results and limitations: With a median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34% (95% confidence interval, 29-39%) and 17% (95% confidence interval, 13-22%) in the ET and ET + RAD arms respectively (p < 0.001). Compared with the ET arm, the median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment with ET alone, age >= 65 yr and increasing histology grade independently increased the risk of PCa-specific and overall mortality. Limitations include nonformal evaluation of comorbidity, the inability to calculate progression-free survival, and lack of information about salvage therapy and toxicity. Conclusions: In patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone; the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high-risk PCa. Patient summary: Adding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis. 

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