@article{BeckTitzeHuebneretal.2015,
  author    = {Beck, Hanna and Titze, Stephanie I. and H{\"u}bner, Silvia and Busch, Martin and Schlieper, Georg and Schultheiss, Ulla T. and Wanner, Christoph and Kronenberg, Florian and Krane, Vera and Eckardt, Kai-Uwe and K{\"o}ttgen, Anna},
  title     = {Heart Failure in a Cohort of Patients with Chronic Kidney Disease: The GCKD Study},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0122552},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143315},
  pages     = {e0122552},
  year      = {2015},
  abstract  = {Background and Aims Chronic kidney disease (CKD) is a risk factor for development and progression of heart failure (HF). CKD and HF share common risk factors, but few data exist on the prevalence, signs and symptoms as well as correlates of HF in populations with CKD of moderate severity. We therefore aimed to examine the prevalence and correlates of HF in the German Chronic Kidney Disease (GCKD) study, a large observational prospective study. Methods and Results We analyzed data from 5,015 GCKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m\(^{2}\) or with an eGFR >= 60 and overt proteinuria (>500 mg/d). We evaluated a definition of HF based on the Gothenburg score, a clinical HF score used in epidemiological studies (Gothenburg HF), and self-reported HF. Factors associated with HF were identified using multivariable adjusted logistic regression. The prevalence of Gothenburg HF was 43\% (ranging from 24\% in those with eGFR >90 to 59\% in those with eGFR<30 ml/min/1.73m2). The corresponding estimate for self-reported HF was 18\% (range 5\%-24\%). Lower eGFR was significantly and independently associated with the Gothenburg definition of HF (p-trend <0.001). Additional significantly associated correlates included older age, female gender, higher BMI, hypertension, diabetes mellitus, valvular heart disease, anemia, sleep apnea, and lower educational status. Conclusions The burden of self-reported and Gothenburg HF among patients with CKD is high. The proportion of patients who meet the criteria for Gothenburg HF in a European cohort of patients with moderate CKD is more than twice as high as the prevalence of self-reported HF. However, because of the shared signs, symptoms and medications of HF and CKD, the Gothenburg score cannot be used to reliably define HF in CKD patients. Our results emphasize the need for early screening for HF in patients with CKD.},
  language  = {en}
}
@article{BuschNadalSchmidetal.2016,
  author    = {Busch, Martin and Nadal, Jennifer and Schmid, Matthias and Paul, Katharina and Titze, Stephanie and H{\"u}bner, Silvia and K{\"o}ttgen, Anna and Schultheiss, Ulla T. and Baid-Agrawal, Seema and Lorenzen, Johan and Schlieper, Georg and Sommerer, Claudia and Krane, Vera and Hilge, Robert and Kielstein, Jan T. and Kronenberg, Florian and Wanner, Christoph and Eckardt, Kai-Uwe and Wolf, Gunter},
  title     = {Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort},
  series = {BMC Nephrology},
  volume    = {17},
  journal   = {BMC Nephrology},
  number    = {59},
  doi       = {10.1186/s12882-016-0273-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164687},
  year      = {2016},
  abstract  = {Background Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results At baseline, DM was present in 1842 patients (35 \%) and the median HbA1C was 7.0 \% (25th-75th percentile: 6.8-7.9 \%), equalling 53 mmol/mol (51, 63); 24.2 \% of patients received dietary treatment only, 25.5 \% oral antidiabetic drugs but not insulin, 8.4 \% oral antidiabetic drugs with insulin, and 41.8 \% insulin alone. Metformin was used by 18.8 \%. Factors associated with an HbA1C level >7.0 \% (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 \% CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 \% CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 \% CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 \% CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 \% receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.},
  language  = {en}
}
@article{CarstenAGorskiLietal.2011,
  author    = {Carsten A., B{\"o}ger and Gorski, Mathias and Li, Man and Hoffmann, Michael M. and Huang, Chunmei and Yang, Qiong and Teumer, Alexander and Krane, Vera and O'Seaghdha, Conall M. and Kutalik, Zolt{\´a}n and Wichmann, H.-Erich and Haak, Thomas and Boes, Eva and Coassin, Stefan and Coresh, Josef and Kollerits, Barbara and Haun, Margot and Paulweber, Bernhard and K{\"o}ttgen, Anna and Li, Guo and Shlipak, Michael G. and Powe, Neil and Hwang, Shih-Jen and Dehghan, Abbas and Rivadeneira, Fernando and Uitterlinden, Andr{\´e} and Hofman, Albert and Beckmann, Jacques S. and Kr{\"a}mer, Bernhard K. and Witteman, Jacqueline and Bochud, Murielle and Siscovick, David and Rettig, Rainer and Kronenberg, Florian and Wanner, Christoph and Thadhani, Ravi I. and Heid, Iris M. and Fox, Caroline S. and Kao, W.H.},
  title     = {Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD},
  series = {PLoS Genetics},
  volume    = {7},
  journal   = {PLoS Genetics},
  number    = {9},
  doi       = {10.1371/journal.pgen.1002292},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133758},
  pages     = {e1002292},
  year      = {2011},
  abstract  = {Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.},
  language  = {en}
}
@article{DrechslerKolleritzMeinitzeretal.2013,
  author    = {Drechsler, Christiane and Kolleritz, Barbara and Meinitzer, Andreas and M{\"a}rz, Winfried and Ritz, Eberhard and K{\"o}nig, Paul and Neyer, Ulrich and Pilz, Stefan and Wanner, Christoph and Kronenberg, Florian},
  title     = {Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  organization    = {MMKD Study Group},
  doi       = {10.1371/journal.pone.0063560},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130979},
  pages     = {e63560},
  year      = {2013},
  abstract  = {Background: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD). Methods: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. Results: Study participants were at baseline on average 47 \(\pm\)13 years old and 65\% were male. Mean \(\pm\) standard deviation of homoarginine concentrations were \(2.5 \pm 1.1 \mu mol/L\) and concentrations were incrementally lower at lower levels of GFR with mean concentrations of \(2.90 \pm 1.02 \mu mol/L\) (GFR. 90 ml/min), \(2.64 \pm 1.06 \mu mol/L\) (GFR 60-90 ml/min), \(2.52 \pm 1.24 \mu mol/L\) (GFR 30-60 ml/min) and \(2.05 \pm 0.78 \mu mol/L\) (GFR, 30 ml/min), respectively (p = 0.002). The age-and sex-adjusted risk to reach the renal endpoint was significantly higher by 62\% with each decrease by one standard deviation (\(1.1 \mu mol/L\)) of homoarginine (HR 1.62, 95\% CI 1.16-2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95\% CI 1.11-2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95\% CI 0.98-1.98, p = 0.06). Conclusions: Homoarginine concentrations are directly correlated with kidney function and are significantly associated with the progression of CKD. Low homoarginine concentrations might be an early indicator of kidney failure and a potential target for the prevention of disease progression which needs further investigations.},
  language  = {en}
}
@article{KressHuettenhoferLandryetal.2013,
  author    = {Kress, Michaela and H{\"u}ttenhofer, Alexander and Landry, Marc and Kuner, Rohini and Favereaux, Alexandre and Greenberg, David and Bednarik, Josef and Heppenstall, Paul and Kronenberg, Florian and Malcangio, Marzia and Rittner, Heike and {\"U}{\c{c}}eyler, Nurcan and Trajanoski, Zlatko and Mouritzen, Peter and Birklein, Frank and Sommer, Claudia and Soreq, Hermona},
  title     = {microRNAs in nociceptive circuits as predictors of future clinical applications},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {6},
  journal   = {Frontiers in Molecular Neuroscience},
  number    = {33},
  doi       = {10.3389/fnmol.2013.00033},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154597},
  year      = {2013},
  abstract  = {Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs - and microRNAs (miRNAs) in particular - regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.},
  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}
}