@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{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{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{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}
}