@phdthesis{Cejka2024, author = {Cejka, Vladimir}, title = {Prognostische Relevanz von Fettgewebesurrogaten bei Patienten mit chronischer Niereninsuffizienz - Auswertungen der prospektiven German Chronic Kidney Disease Studie}, doi = {10.25972/OPUS-34926}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349266}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Einleitung: In dieser Arbeit wurde die Auswirkung der Fettgewebesurrogate Halsumfang (HU), Taillenumfang (TU) und Body Mass Index (BMI) auf die Prognose bei Patienten mit chronischer Niereninsuffizienz untersucht. Methoden: Datengrundlage dieser Arbeit war die German Chronic Kidney Disease (GCKD) Beobachtungsstudie. Eingeschlossen wurden Erwachsene mit GFR 30-60 ml/min/1,73m² oder GFR > 60 ml/min/1,73m² mit offensichtlicher Proteinurie. Ausschlusskriterien waren: nicht-kaukasische Ethnie, Organtransplantation, Malignome und Herzinsuffizienz NYHA IV. Untersuchte kombinierte Endpunkte (EP) waren: 1) 4P-MACE (Herzinfarkt, Schlaganfall, kardiovaskul{\"a}rer Tod, pAVK-Ereignis) 2) Tod jeglicher Ursache 3) Nierenversagen (Dialyse, Transplantation). Es wurden Cox-Regressionen mit HU, TU, und BMI f{\"u}r jeden EP, adjustiert f{\"u}r Alter, Geschlecht, Nikotinkonsum, Diabetes mellitus, arterielle Hypertonie, LDL-Cholesterin, GFR, Urin-Albumin/Kreatinin Ratio (UACR) und CRP berechnet. Interaktionsterme des jeweiligen Surrogats mit dem Geschlecht wurden eingeschlossen. Ergebnisse: Von den 4537 analysierten Studienteilnehmern, waren 59\% M{\"a}nner mit einem Durchschnittsalter von 60 (±12) Jahren, einer mittleren GFR von 50 (±18) ml/min/1,73m² und einem UACR-Median von 49 (10-374) mg/g. Der mittlere HU war 42,7 (±3,6) cm bei M{\"a}nnern und 37,2 (±3,7) cm bei Frauen, der mittlere TU 107,6 (±13,6) cm bei M{\"a}nnern und 97,0 (±16,3) cm bei Frauen und der mittlere BMI 29,7 (±5,9) kg/m². Die mittlere Beobachtungszeit betrug 6,5 Jahre. Der TU war signifikant mit Tod assoziiert, mit einer HR von 1,014 pro cm (95\% KI 1,005-1,024). HU war signifikant mit Tod bei Frauen assoziiert, Interaktionsterm HR 1,080 pro cm (95\% KI 1,009-1,155). Der BMI hatte keinen signifikanten Einfluss auf untersuchte EP. Schlussfolgerung: Bei Patienten mit mittel- bis schwergradig eingeschr{\"a}nkter Nierenfunktion steigern ein erh{\"o}hter TU (bei beiden Geschlechtern), sowie bei Frauen ein erh{\"o}hter HU das Risiko f{\"u}r Tod jeglicher Ursache.}, subject = {Fettsucht}, language = {de} } @article{GerhardtKordsmeyerSehneretal.2023, author = {Gerhardt, Louisa M. S. and Kordsmeyer, Maren and Sehner, Susanne and G{\"u}der, G{\"u}lmisal and St{\"o}rk, Stefan and Edelmann, Frank and Wachter, Rolf and Pankuweit, Sabine and Prettin, Christiane and Ertl, Georg and Wanner, Christoph and Angermann, Christiane E.}, title = {Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages}, series = {Clinical Research in Cardiology}, volume = {112}, journal = {Clinical Research in Cardiology}, number = {7}, doi = {10.1007/s00392-022-02027-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323990}, pages = {868-879}, year = {2023}, abstract = {Background The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A-D. Methods and results 2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1\%/35.3\%/32.9\% and 23.7\% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( - ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3\%/23.6\%/31.6\%/54.7\%; anaemia: 3.0\%/7.9\%/21.7\%/33.2\%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95\% confidence intervals] for all-cause mortality were 2.1 [1.8-2.6] for CKD + , 1.7 [1.4-2.0] for anaemia, and 3.6 [2.9-4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4\%, 30.8\% and 34.7\%, respectively). Conclusions Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.}, language = {en} } @article{MaglioccaMoneDiIorioetal.2022, author = {Magliocca, Giorgia and Mone, Pasquale and Di Iorio, Biagio Raffaele and Heidland, August and Marzocco, Stefania}, title = {Short-chain fatty acids in Chronic Kidney Disease: focus on inflammation and oxidative stress regulation}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {10}, issn = {1422-0067}, doi = {10.3390/ijms23105354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284587}, year = {2022}, abstract = {Chronic Kidney Disease (CKD) is a debilitating disease associated with several secondary complications that increase comorbidity and mortality. In patients with CKD, there is a significant qualitative and quantitative alteration in the gut microbiota, which, consequently, also leads to reduced production of beneficial bacterial metabolites, such as short-chain fatty acids. Evidence supports the beneficial effects of short-chain fatty acids in modulating inflammation and oxidative stress, which are implicated in CKD pathogenesis and progression. Therefore, this review will provide an overview of the current knowledge, based on pre-clinical and clinical evidence, on the effect of SCFAs on CKD-associated inflammation and oxidative stress.}, language = {en} } @article{KoepingShehataDielerSchneideretal.2018, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Schneider, Dieter and Cebulla, Mario and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian P.}, title = {Characterization of vertigo and hearing loss in patients with Fabry disease}, series = {Orphanet Journal of Rare Diseases}, volume = {13}, journal = {Orphanet Journal of Rare Diseases}, doi = {10.1186/s13023-018-0882-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222818}, year = {2018}, abstract = {Background Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions. Methods Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results More than one out of three patients (35.1\%) complained about hearing loss, 54.4\% about vertigo and 28.1\% about both symptom. In 74\% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9\%, VEMPs were pathological in 68\%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed. Conclusions Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.}, language = {en} } @article{deZeeuwAkizawaAgarwaletal.2013, author = {de Zeeuw, Dick and Akizawa, Tadao and Agarwal, Rajiv and Audhya, Paul and Bakris, George L. and Chin, Melanie and Krauth, Melissa and Lambers Heerspink, Hiddo J. and Meyer, Colin J. and McMurray, John J. and Parving, Hans-Henrik and Pergola, Pablo E. and Remuzzi, Giuseppe and Toto, Robert D. and Vaziri, Nosratola D. and Wanner, Christoph and Warnock, David G. and Wittes, Janet and Chertow, Glenn M.}, title = {Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON)}, series = {American Journal of Nephrology}, volume = {37}, journal = {American Journal of Nephrology}, number = {3}, issn = {0250-8095}, doi = {10.1159/000346948}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196832}, pages = {212-222}, year = {2013}, abstract = {Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Methods: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. Results: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.}, language = {en} } @article{DannewitzSommererStoelzeletal.2020, author = {Dannewitz, Bettina and Sommerer, Claudia and St{\"o}lzel, Peggy and Baid-Agrawal, Seema and Nadal, Jennifer and B{\"a}rthlein, Barbara and Wanner, Christoph and Eckardt, Kai-Uwe and Zeier, Martin and Schlagenhauf, Ulrich and Krane, Vera and Jockel-Schneider, Yvonne}, title = {Status of periodontal health in German patients suffering from chronic kidney disease—Data from the GCKD study}, series = {Journal of Clinical Periodontology}, volume = {47}, journal = {Journal of Clinical Periodontology}, number = {1}, doi = {10.1111/jcpe.13208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217821}, pages = {19 -- 29}, year = {2020}, abstract = {Aim To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. Material and methods The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. Results 24.4\% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6\% displayed moderate and 27\% severe periodontitis. Questionnaire data revealed that 62.3\% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4\% denied having received any systematic periodontal therapy so far, although 50\% of them indicated to visit their dentist regularly for professional tooth cleanings. Conclusion While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.}, language = {en} } @article{MacdougallBircherEckhardtetal.2016, author = {Macdougall, Iain C. and Bircher, Andreas J. and Eckhardt, Kai-Uwe and Obrador, Gregorio T. and Pollock, Carol A. and Stenvinkel, Peter and Swinkels, Dorine W. and Wanner, Christoph and Weiss, G{\"u}nter and Chertow, Glenn M.}, title = {Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference}, series = {Kidney International}, volume = {89}, journal = {Kidney International}, number = {1}, doi = {10.1016/j.kint.2015.10.002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191467}, pages = {28-39}, year = {2016}, abstract = {Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.}, language = {en} } @article{RotheBrandenburgHaunetal.2017, author = {Rothe, Hansj{\"o}rg and Brandenburg, Vincent and Haun, Margot and Kollerits, Barbara and Kronenberg, Florian and Ketteler, Markus and Wanner, Christoph}, title = {Ecto-5 ' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients - Data from the German Calciphylaxis Registry}, series = {PLoS One}, volume = {12}, journal = {PLoS One}, number = {2}, doi = {10.1371/journal.pone.0172407}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171817}, year = {2017}, abstract = {Introduction: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. Methods: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD). 144 dialysis patients from the German calciphylaxis registry were compared with 370 dialysis patients without history of CUA. Genotyping was performed using iPLEX Gold MassARRAY(Sequenom, San Diego, USA), KASP genotyping chemistry (LGC, Teddington, Middlesex, UK) or sequencing. Statistical analysis comprised logistic regression analysis with adjustment for age and sex. Results: 165 SNPs were finally analyzed and 6 SNPs were associated with higher probability for calciphylaxis (OR>1) in our cohort. Nine SNPs of three genes (CD73, FGF23 and Vitamin D receptor) reached nominal significance (p< 0.05), but did not reach statistical significance after correction for multiple testing. Of the CD73 gene, rs4431401 (OR = 1.71, 95\%CI 1.08-2.17, p = 0.023) and rs9444348 (OR = 1.48, 95\% CI 1.11-1.97, p = 0.008) were associated with a higher probability for CUA. Of the FGF23 and VDR genes, rs7310492, rs11063118, rs13312747 and rs17882106 were associated with a higher probability for CUA. Conclusion: Polymorphisms in the genes encoding CD73, vitamin D receptor and FGF23 may play a role in calciphylaxis development. Although our study is the largest genetic study on calciphylaxis, it is limited by the low sample sizes. It therefore requires replication in other cohorts if available.}, language = {en} } @article{PerkovicAgarwalFiorettoetal.2016, author = {Perkovic, Vlado and Agarwal, Rajiv and Fioretto, Paola and Hemmelgarn, Brenda R. and Levin, Adeera and Thomas, Merlin C. and Wanner, Christoph and Kasiske, Bertram L. and Wheeler, David C. and Groop, Per-Henrik}, title = {Management of patients with diabetes and CKD: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) controversies conference}, series = {Kidney International}, volume = {90}, journal = {Kidney International}, number = {6}, doi = {10.1016/j.kint.2016.09.010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186599}, pages = {1175-1183}, year = {2016}, abstract = {The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.}, language = {en} } @article{MarzoccoFazeliDiMiccoetal.2018, author = {Marzocco, Stefania and Fazeli, Gholamreza and Di Micco, Lucia and Autore, Giuseppina and Adesso, Simona and Dal Piaz, Fabrizio and Heidland, August and Di Iorio, Biagio}, title = {Supplementation of short-chain fatty acid, sodium propionate, in patients on maintenance hemodialysis: beneficial effects on inflammatory parameters and gut-derived uremic toxins, a pilot study (PLAN Study)}, series = {Journal of Clinical Medicine}, volume = {7}, journal = {Journal of Clinical Medicine}, number = {10}, issn = {2077-0383}, doi = {10.3390/jcm7100315}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197626}, pages = {315}, year = {2018}, abstract = {Background: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates. Aim of the study: The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation. Study design: We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning, after six weeks and at the end of the administration period, as well as four weeks after withdrawal of the treatment. Results: The subjects revealed a significant decline of inflammatory parameters C-reactive protein (-46\%), interleukin IL-2 (-27\%) and IL-17 (-15\%). The inflammatory parameters IL-6 and IFN-gamma showed a mild non-significant reduction and the anti-inflammatory cytokine IL-10 increased significantly (+71\%). While the concentration of bacterial endotoxins and TNF-α remained unchanged, the gut-derived uremic toxins, indoxyl sulfate (-30\%) and p-cresyl sulfate (-50\%), revealed a significant decline. The SP supplementation reduced the parameters of oxidative stress malondialdehyde (-32\%) and glutathione peroxidase activity (-28\%). The serum insulin levels dropped by 30\% and the HOMA-index by 32\%. The reduction of inflammatory parameters was associated with a lowering of ferritin and a significant increase in transferrin saturation (TSAT). Four weeks after the end of the treatment phase, all improved parameters deteriorated again. Evaluation of the psycho-physical performance with the short form 36 (SF-36) questionnaire showed an enhancement in the self-reported physical functioning, general health, vitality and mental health. The SP supplementation was well tolerated and without important side effects. No patient had left the study due to intolerance to the medication. The SP supplementation in MHD patients reduced pro-inflammatory parameters and oxidative stress and improved insulin resistance and iron metabolism. Furthermore, SP effectively lowered the important gut-derived uremic toxins indoxyl and p-cresol sulfate. These improvements were associated with a better quality of life. Further controlled studies are required in a larger cohort to evaluate the clinical outcome.}, language = {en} } @phdthesis{Triebswetter2019, author = {Triebswetter, Susanne}, title = {Charakterisierung von Langzeit{\"u}berlebenden in einem Kollektiv h{\"a}modialysepflichtiger Patienten mit Typ 2 Diabetes}, doi = {10.25972/OPUS-18982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189821}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Die Mortalit{\"a}tsrate von Dialysepatienten ist gegen{\"u}ber der Allgemeinbev{\"o}lkerung deutlich erh{\"o}ht; im Besonderen bei Patienten, die zugleich an einem Diabetes mellitus Typ 2 leiden. Es gibt zahlreiche Studien, die versuchen, Pr{\"a}diktoren f{\"u}r das Kurz- und Langzeit{\"u}berleben von Dialysepatienten zu ermitteln. Studien, die dasselbe f{\"u}r h{\"a}modialysepflichtige Patienten mit Typ 2 Diabetes mellitus versuchen, sind jedoch noch selten. Ziel der vorliegenden Arbeit war es, die {\"U}berlebenden der Deutschen Diabetes Dialyse Studie (4D Studie) zu charakterisieren und {\"U}berlebenszeitanalysen durchzuf{\"u}hren, um Hypothesen f{\"u}r zuk{\"u}nftige Studien zu generieren und m{\"o}gliche Risikofaktoren f{\"u}r eine erh{\"o}hte Mortalit{\"a}t zu ermitteln. In der vorliegenden Arbeit wurden mit Hilfe der Daten der 4D-Studie {\"U}berlebenszeitanalysen f{\"u}r 1255 h{\"a}modialysepflichtige Patienten mit Diabetes mellitus Typ 2 aus 178 Dialysezentren in Deutschland durchgef{\"u}hrt (mittlere Beobachtungsdauer: 11,5 Jahre). Der prim{\"a}re Endpunkt war die Gesamtmortalit{\"a}t. Mit dem Cox Proportional Hazards Modell wurden Hazard Ratios f{\"u}r zehn ausgew{\"a}hlte Parameter (Alter, Geschlecht, Pflege, Body Mass Index, Albumin, Diabetesdauer, HbA1c, und kardiovaskul{\"a}re, zerebrovaskul{\"a}re, periphere vaskul{\"a}re Vorerkrankungen) sowohl f{\"u}r das gesamte Kollektiv als auch f{\"u}r nach Geschlecht, Alter und Diabetesdauer aufgeteilte Subgruppen berechnet. Anschließend wurden f{\"u}r alle drei Subgruppen Interaktionsanalysen durchgef{\"u}hrt. Die {\"U}berlebenden des gesamten Studienzeitraumes von 11,5 Jahren sind im Durchschnitt j{\"u}nger und h{\"a}ufiger m{\"a}nnlich, haben weniger Vorerkrankungen und sind seltener pflegebed{\"u}rftig, sind k{\"u}rzer an Diabetes mellitus erkrankt, das HbA1c ist besser eingestellt und BMI und Serumalbumin liegen h{\"o}her als bei den Verstorbenen. Pflegebed{\"u}rftigkeit (HR = 1,199, p = 0,018), ein niedriges Serumalbumin (HR = 0,723, p = 0,002) sowie kardiovaskul{\"a}re (HR = 1,423, p < 0,001) und periphere vaskul{\"a}re Erkrankungen (HR = 1,549, p < 0,001) erh{\"o}hen das Mortalit{\"a}tsrisiko signifikant. Weibliche Patienten verlieren ihren, in der Gesamtbev{\"o}lkerung {\"u}blichen, {\"U}berlebensvorteil (HR = 1,019, p < 0,79).}, subject = {Chronische Niereninsuffizienz}, language = {de} } @article{SchuppStopperHeidland2016, author = {Schupp, Nicole and Stopper, Helga and Heidland, August}, title = {DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers}, series = {Oxidative Medicine and Cellular Longevity}, volume = {2016}, journal = {Oxidative Medicine and Cellular Longevity}, number = {3592042}, doi = {10.1155/2016/3592042}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166569}, year = {2016}, abstract = {Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients' burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker's potential to predict clinical outcomes.}, language = {en} } @phdthesis{Wagner2019, author = {Wagner, Martin}, title = {Chronic Kidney Disease as an Important Co-morbid Condition in Coronary Heart Disease Patients}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175498}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {In patients with coronary heart disease (CHD) the control of the modifiable "traditional" cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, achieving/maintaining normal body weight and smoking cessation is of major importance to improve prognosis. Guideline recommendations for secondary CHD prevention include specific treatment targets for blood pressure, lipid levels, and markers of glucose metabolism for both younger and older patients. Chronic kidney disease (CKD) has been identified as a "non-traditional" risk factor for worse outcome in CHD patients, as it is associated with a markedly increased risk for subsequent CV events and mortality. The specific objectives of the current thesis-project are to investigate (a) the quality of care in a recent sample of German CHD patients and to investigate variation of risk factor control between younger and elder patients (≤70 versus >70 years), (b) to analyze the prevalence of CKD across Europe in stable CHD patients in the outpatient setting and during a hospital stay for CHD, (c) to investigate the level of awareness of CKD in German CHD patients and their treating physicians. Data from the European-wide EUROASPIRE IV study were used that include data on 7998 CHD patients in the ambulatory setting (study visit) and during a hospital stay for CHD (index). The German EUROASPIRE IV study center in W{\"u}rzburg recruited 536 patients in 2012-2013. Risk factor control was compared against the current recommendations of the European Society of Cardiology. CKD was described by stages of glomerular filtration rate (eGFR) and albuminuria. German patients were asked in an additional kidney specific module whether they have ever been told by a physician about renal impairment. The fact that CKD or acute kidney injury (AKI) was mentioned in prominent parts of the hospital discharge letter as well as correct ICD-coding of CKD or AKI served as a proxy for physician's awareness of CKD. The majority of German CHD patients was treated with the recommended drug therapies including e.g. β-blockers, anti-platelets and statins. However, treatment targets for blood pressure and LDL-cholesterol levels were not achieved in many patients (45\% and 53\%, respectively) and glycemic control in diabetic CHD patients with HbA1-levels <7\% was insufficient (61\%). A minority of patients reported on current smoking (10\%), but unhealthy life-styles e.g. overweight/obesity (85\%/37\%) were frequent. Patterns of care differed between younger and older CHD patients while older patients were less likely to receive the recommended medical CHD-therapy, were more likely to have uncontrolled blood pressure and also to be diabetic. However, a greater proportion of diabetic patients >70 years was achieving the HbA1c target, and less elder patients were current smokers or were obese. About 17\% of patients on average had CKD (eGFR< 60 ml/min/1.73m²) in the entire European sample at the study visit, and an additional 10\% had albuminuria despite preserved eGFR, with considerable variation among countries. Impaired kidney function was observed in every fifth patient admitted for CHD in the entire European dataset of the EUROASPIRE IV study. Of the German CHD patients with CKD at the study visit, only a third were aware of their renal impairment. A minority of these patients was being seen by nephrologists, however, with a higher likelihood of CKD awareness and specialist care in more advanced stages of CKD. About a third of patients admitted for CHD showed either CKD or AKI during the hospital stay, but the discharge letter mentioned chronic or acute kidney disease only in every fifth of these patients. In contrast, correct ICD coding of CKD or AKI was more complete, but still suboptimal. In summary, quality of secondary prevention in German CHD patients indicates considerably room for improvement, with life-style modifications may become an even greater factor in prevention campaigns than medical treatment into certain target ranges. Preventive therapies should also consider different needs in older individuals acknowledging physical and mental potential, other comorbidities and drug-interactions with co-medication. CKD is common in CHD patients, not only in the elderly. Since CHD and CKD affect each other and impact on worse prognosis of each other, raising the awareness of CKD among patients and physicians and considering CKD in medical therapy may improve prognosis and slow disease progression of CHD as well as CKD.}, language = {en} } @article{SchneiderSchneiderKrieteretal.2015, author = {Schneider, Andreas and Schneider, Markus P. and Krieter, Detlef H. and Genser, Bernd and Scharnagl, Hubert and Stojakovic, Tatjana and Wanner, Christoph and Drechsler, Christiane}, title = {Effect of high-flux dialysis on circulating FGF-23 levels in end-stage renal disease patients: results from a randomized trial}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0128079}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148559}, pages = {e0128079}, year = {2015}, abstract = {Background In patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. Interventional strategies aiming to reduce levels of FGF-23 in HD patients are of particular interest. The purpose of the current study was to compare the impact of high-flux versus low-flux HD on circulating FGF-23 levels. Methods We conducted a post-hoc analysis of the MINOXIS study, including 127 dialysis patients randomized to low-flux (n = 62) and high-flux (n = 65) HD for 52 weeks. Patients with valid measures for FGF-23 investigated baseline and after 52 weeks were included. Results Compared to baseline, a significant increase in FGF-23 levels after one year of low-flux HD was observed (Delta plasma FGF-23: +4026 RU/ml; p < 0.001). In contrast, FGF-23 levels remained stable in the high flux group (Delta plasma FGF-23: +373 RU/ml, p = 0.70). The adjusted difference of the absolute change in FGF-23 levels between the two treatment groups was statistically significant (p < 0.01). Conclusions Over a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23. However, the implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in specifically designed clinical trials.}, language = {en} } @article{WagnerWannerSchichetal.2017, author = {Wagner, Martin and Wanner, Christoph and Schich, Martin and Kotseva, Kornelia and Wood, David and Hartmann, Katrin and Fette, Georg and R{\"u}cker, Viktoria and Oezkur, Mehmet and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Patient's and physician's awareness of kidney disease in coronary heart disease patients - a cross-sectional analysis of the German subset of the EUROASPIRE IV survey}, series = {BMC Nephrology}, volume = {18}, journal = {BMC Nephrology}, number = {321}, doi = {10.1186/s12882-017-0730-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158387}, year = {2017}, abstract = {Background Chronic kidney disease (CKD) is a common comorbid condition in coronary heart disease (CHD). CKD predisposes the patient to acute kidney injury (AKI) during hospitalization. Data on awareness of kidney dysfunction among CHD patients and their treating physicians are lacking. In the current cross-sectional analysis of the German EUROASPIRE IV sample we aimed to investigate the physician's awareness of kidney disease of patients hospitalized for CHD and also the patient's awareness of CKD in a study visit following hospital discharge. Methods All serum creatinine (SCr) values measured during the hospital stay were used to describe impaired kidney function (eGFR\(_{CKD-EPI}\) < 60 ml/min/1.73m2) at admission, discharge and episodes of AKI (KDIGO definition). Information extracted from hospital discharge letters and correct ICD coding for kidney disease was studied as a surrogate of physician's awareness of kidney disease. All patients were interrogated 0.5 to 3 years after hospital discharge, whether they had ever been told about kidney disease by a physician. Results Of the 536 patients, 32\% had evidence for acute or chronic kidney disease during the index hospital stay. Either condition was mentioned in the discharge letter in 22\%, and 72\% were correctly coded according to ICD-10. At the study visit in the outpatient setting 35\% had impaired kidney function. Of 158 patients with kidney disease, 54 (34\%) were aware of CKD. Determinants of patient's awareness were severity of CKD (OR\(_{eGFR}\) 0.94; 95\%CI 0.92-0.96), obesity (OR 1.97; 1.07-3.64), history of heart failure (OR 1.99; 1.00-3.97), and mentioning of kidney disease in the index event's hospital discharge letter (OR 5.51; 2.35-12.9). Conclusions Although CKD is frequent in CHD, only one third of patients is aware of this condition. Patient's awareness was associated with kidney disease being mentioned in the hospital discharge letter. Future studies should examine how raising physician's awareness for kidney dysfunction may improve patient's awareness of CKD.}, language = {en} } @article{BiermannHeilmannDidieetal.2012, author = {Biermann, Daniel and Heilmann, Andreas and Didi{\´e}, Michael and Schlossarek, Saskia and Wahab, Azadeh and Grimm, Michael and R{\"o}mer, Maria and Reichenspurner, Hermann and Sultan, Karim R. and Steenpass, Anna and Erg{\"u}n, S{\"u}leyman and Donzelli, Sonia and Carrier, Lucie and Ehmke, Heimo and Zimmermann, Wolfram H. and Hein, Lutz and B{\"o}ger, Rainer H. and Benndorf, Ralf A.}, title = {Impact of AT2 Receptor Deficiency on Postnatal Cardiovascular Development}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0047916}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134902}, pages = {e47916}, year = {2012}, abstract = {Background: The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear. Methodology/Principal Findings: Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of \(\alpha\)-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca\(^{2+}\) transient in response to isoprenaline when stimulated concomitantly with angiotensin II. Conclusion: The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.}, language = {en} } @article{KleikersHooijmansGoebetal.2015, author = {Kleikers, Pamela W. M. and Hooijmans, Carlijn and G{\"o}b, Eva and Langhauser, Friederike and Rewell, Sarah S. J. and Radermacher, Kim and Ritskes-Hoitinga, Merel and Howells, David W. and Kleinschnitz, Christoph and Schmidt, Harald H. H. W.}, title = {A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {13428}, doi = {10.1038/srep13428}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151401}, year = {2015}, abstract = {Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX\(_{2}\) to be a major therapeutic target in stroke. Systematic review and MA of all available NOX\(_{2}\)\(^{-/y}\) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX\(_{2}\) as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.}, language = {en} } @article{OderVerghoErtletal.2016, author = {Oder, Daniel and Vergho, Dorothee and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter}, title = {Case report of a 45-year old female Fabry disease patient carrying two alpha-galactosidase A gene mutation alleles}, series = {BMC Medical Genetics}, volume = {17}, journal = {BMC Medical Genetics}, number = {46}, doi = {10.1186/s12881-016-0309-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146617}, year = {2016}, abstract = {Background X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown. Case presentation This article reports on a 45 year old female patient carrying the two alpha-galactosidase A gene mutations c.416A > G, p.N139S in exon 3 and c.708G > C, p.W236C in exon 5, but still showing only mild organ manifestations. Conclusion This current case highlights the importance of careful clinical characterization in patients with Fabry disease, who may show additional rare constellations and, therefore, are in need of personalized medicine. The impact of potential additional protective effects exceeding the presence of a non-pathogenic GLA allele in female gene carriers requires further investigation.}, language = {en} } @article{PalkovitsŠebekovaKlenovicsetal.2013, author = {Palkovits, Mikl{\´o}s and Šebekov{\´a}, Katar{\´i}na and Klenovics, Kristina Simon and Kebis, Anton and Fazeli, Gholamreza and Bahner, Udo and Heidland, August}, title = {Neuronal Activation in the Central Nervous System of Rats in the Initial Stage of Chronic Kidney Disease-Modulatory Effects of Losartan and Moxonidine}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0066543}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130108}, pages = {e66543}, year = {2013}, abstract = {The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively. In 37 brain areas/nuclei several neurons with different functional properties were strongly affected in 4/6NX. It elicited a moderate to high Fos-activity in areas responsible for the monoaminergic innervation of the cerebral cortex, the limbic system, the thalamus and hypothalamus (e.g. noradrenergic neurons of the locus coeruleus, serotonergic neurons in dorsal raphe, histaminergic neurons in the tuberomamillary nucleus). Other monoaminergic cell groups (A5 noradrenaline, C1 adrenaline, medullary raphe serotonin neurons) and neurons in the hypothalamic paraventricular nucleus (innervating the sympathetic preganglionic neurons and affecting the peripheral sympathetic outflow) did not show Fos-activity. Stress- and pain-sensitive cortical/subcortical areas, neurons in the limbic system, the hypothalamus and the circumventricular organs were also affected by 4/6NX. Administration of losartan and more strongly moxonidine modulated most effects and particularly inhibited Fos-activity in locus coeruleus neurons. In conclusion, 4/6NX elicits high activity in central sympathetic, stress- and pain-related brain areas as well as in the limbic system, which can be ameliorated by losartan and particularly by moxonidine. These changes indicate a high sensitivity of CNS in initial stages of CKD which could be causative in clinical disturbances.}, language = {en} } @article{LocatelliSpasovskiDimkovicetal.2014, author = {Locatelli, Francesco and Spasovski, Goce and Dimkovic, Nada and Wanner, Christoph and Dellanna, Frank and Pontoriero, Giuseppe}, title = {The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study}, series = {Nephrology Dialysis Transplantation}, volume = {29}, journal = {Nephrology Dialysis Transplantation}, number = {5}, doi = {10.1093/ndt/gft476}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121114}, pages = {1061-73}, year = {2014}, abstract = {BACKGROUND: This study compared the effects of short-term titrated colestilan (a novel non-absorbable, non-calcium, phosphate binder) with placebo, and evaluated the safety and efficacy of colestilan over 1 year compared with sevelamer, in patients with chronic kidney disease (CKD) 5D. METHODS: This prospective multicentre study comprised a 4-week phosphate binder washout period, a 16-week short-term, flexible-dose, treatment period (including a 4-week placebo-controlled withdrawal period) and a 40-week extension treatment phase. RESULTS: At Week 16 (the end of the 4-week placebo-controlled withdrawal period), serum phosphorus level was 0.43 mmol/L (1.32 mg/dL) lower with colestilan than placebo (P < 0.001; primary end point). Serum LDL-C level was also lower with colestilan than with placebo (P < 0.001). Both colestilan and sevelamer produced significant reductions from baseline in serum phosphorus levels (P < 0.001), maintained for 1 year, and the proportion of patients achieving target levels of ≤1.78 mmol/L (5.5 mg/dL) or ≤1.95 mmol/L (6.0 mg/dL) at study end were similar (65.3 and 73.3\%, respectively, for colestilan, and 66.9 and 77.4\%, respectively, for sevelamer). Serum calcium level remained stable in the colestilan group but tended to increase slightly in the sevelamer group (end-of-study increase of 0.035 mmol/L over baseline). Both binders produced similar reductions from baseline in LDL-C level (P < 0.001), and responder rates after 1 year, using a target of <1.83 mmol/L (70 mg/dL) or <2.59 mmol/L (100 mg/dL) were similar in both groups (50.7 and 85.3\% for colestilan and 54.0 and 80.6\% for sevelamer). Colestilan was generally well tolerated. CONCLUSIONS: Colestilan is effective and safe for the treatment of hyperphosphataemia in patients with CKD 5D, and affords similar long-term phosphorus and cholesterol reductions/responder rates to sevelamer.}, language = {en} }