@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{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{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} } @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{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{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{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} } @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{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{PilgramEberweinWilleetal.2021, author = {Pilgram, Lisa and Eberwein, Lukas and Wille, Kai and Koehler, Felix C. and Stecher, Melanie and Rieg, Siegbert and Kielstein, Jan T. and Jakob, Carolin E. M. and R{\"u}thrich, Maria and Burst, Volker and Prasser, Fabian and Borgmann, Stefan and M{\"u}ller, Roman-Ulrich and Lanznaster, Julia and Isberner, Nora and Tometten, Lukas and Dolff, Sebastian}, title = {Clinical course and predictive risk factors for fatal outcome of SARS-CoV-2 infection in patients with chronic kidney disease}, series = {Infection}, volume = {49}, journal = {Infection}, number = {4}, organization = {LEOSS Study group}, issn = {0300-8126}, doi = {10.1007/s15010-021-01597-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308957}, pages = {725-737}, year = {2021}, abstract = {Purpose The ongoing pandemic caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has stressed health systems worldwide. Patients with chronic kidney disease (CKD) seem to be more prone to a severe course of coronavirus disease (COVID-19) due to comorbidities and an altered immune system. The study's aim was to identify factors predicting mortality among SARS-CoV-2-infected patients with CKD. Methods We analyzed 2817 SARS-CoV-2-infected patients enrolled in the Lean European Open Survey on SARS-CoV-2-infected patients and identified 426 patients with pre-existing CKD. Group comparisons were performed via Chi-squared test. Using univariate and multivariable logistic regression, predictive factors for mortality were identified. Results Comparative analyses to patients without CKD revealed a higher mortality (140/426, 32.9\% versus 354/2391, 14.8\%). Higher age could be confirmed as a demographic predictor for mortality in CKD patients (> 85 years compared to 15-65 years, adjusted odds ratio (aOR) 6.49, 95\% CI 1.27-33.20, p = 0.025). We further identified markedly elevated lactate dehydrogenase (> 2 × upper limit of normal, aOR 23.21, 95\% CI 3.66-147.11, p < 0.001), thrombocytopenia (< 120,000/µl, aOR 11.66, 95\% CI 2.49-54.70, p = 0.002), anemia (Hb < 10 g/dl, aOR 3.21, 95\% CI 1.17-8.82, p = 0.024), and C-reactive protein (≥ 30 mg/l, aOR 3.44, 95\% CI 1.13-10.45, p = 0.029) as predictors, while renal replacement therapy was not related to mortality (aOR 1.15, 95\% CI 0.68-1.93, p = 0.611). Conclusion The identified predictors include routinely measured and universally available parameters. Their assessment might facilitate risk stratification in this highly vulnerable cohort as early as at initial medical evaluation for SARS-CoV-2.}, 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{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} } @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{SteinhardtCejkaChenetal.2024, author = {Steinhardt, Maximilian J. and Cejka, Vladimir and Chen, Mengmeng and B{\"a}uerlein, Sabrina and Sch{\"a}fer, Julia and Adrah, Ali and Ihne-Schubert, Sandra M. and Papagianni, Aikaterini and Kort{\"u}m, K. Martin and Morbach, Caroline and St{\"o}rk, Stefan}, title = {Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study}, series = {Journal of Clinical Medicine}, volume = {13}, journal = {Journal of Clinical Medicine}, number = {1}, issn = {2077-0383}, doi = {10.3390/jcm13010283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-356024}, year = {2024}, abstract = {Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1\% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5\% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.}, language = {en} }