@misc{HocherTsuprykov2017,
  author    = {Hocher, Berthold and Tsuprykov, Oleg},
  title     = {Renoprotective effects of GLP1R agonists and SGLT2 inhibitors},
  series = {Nature reviews nephroloy},
  volume    = {13},
  journal   = {Nature reviews nephroloy},
  publisher = {Nature Publ. Group},
  address   = {New York},
  issn      = {1759-5061},
  doi       = {10.1038/nrneph.2017.140},
  pages     = {728 -- 729},
  year      = {2017},
  abstract  = {New data from the LEADER trial show that the glucagon-like peptide 1 receptor agonist liraglutide protects against diabetic nephropathy in patients with type 2 diabetes mellitus. The renoprotective efficacy of liraglutide is not, however, as great as that reported for the sodium-glucose cotransporter 2 inhibitor emplagiflozin in the EMPA-REG OUTCOME trial.},
  language  = {en}
}
@article{TsuprykovBuseSkobloetal.2018,
  author    = {Tsuprykov, Oleg and Buse, Claudia and Skoblo, Roman and Haq, Afrozul and Hocher, Berthold},
  title     = {Reference intervals for measured and calculated free 25-hydroxyvitamin D in normal pregnancy},
  series = {The Journal of Steroid Biochemistry and Molecular Biology},
  volume    = {181},
  journal   = {The Journal of Steroid Biochemistry and Molecular Biology},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0960-0760},
  doi       = {10.1016/j.jsbmb.2018.03.005},
  pages     = {80 -- 87},
  year      = {2018},
  abstract  = {The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status during pregnancy, since vitamin D-binding protein (DBP) concentrations increase throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP thus strongly influencing total 25(OH)D. The concentration of the biologically active free 25(OH)D - on the other hand - is much less dependent on the DBP concentrations. The study was conducted in May-June 2016 in 368 Caucasian pregnant healthy women - residents of Northeastern Germany. Free 25(OH)D was either measured directly by commercial ELISA kit or assessed by calculation via total 25(OH)D, DBP, and albumin serum concentrations. Regardless of the detection method, free 25(OH)D lowers in the 3rd trimester comparing to the 1st trimester (by 12\% and 21\%, p < 0.05 and p < 0.001, for measured and calculated free 25(OH)D, respectively), whereas total 25(OH)D was not decreased in late pregnancy. DBP rises with gestational age. Total 25(OH)D was not correlated with serum calcium (p = 0.251), whereas free 25(OH)D was significantly (p = 0.007 for measured free 25(OH)D and p < 0.001 for calculated free 25(OH)D) positively correlated with calcium. All 25(OH) D isoforms were significantly negatively correlated with bone-specific alkaline phosphatase (BSAP), however the correlation strength was the lowest with total 25(OH)D (rho = -0.108, p = 0.038), whereas both measured and calculated free 25(OH)D revealed better associations with BSAP (rho = -0.203 and rho = -0.211 for measured and calculated free 25(OH)D, respectively, p < 0.001 for both). We established pregnancy trimester specific reference intervals for free measured and calculated 25(OH)D and DBP. Both measured and calculated free 25(OH)D showed better correlations with parameters of the endocrine vitamin D system (calcium and BSAP). Both ways of measuring free 25(OH)D in pregnant women are suitable as novel laboratory parameter for vitamin D status monitoring during human pregnancy and might replace in the future the routine total 25(OH)D assessment.},
  language  = {en}
}
@article{TsuprykovChenHocheretal.2018,
  author    = {Tsuprykov, Oleg and Chen, Xin and Hocher, Carl-Friedrich and Skoblo, Roman and Yin, Lianghong and Hocher, Berthold},
  title     = {Why should we measure free 25(OH) vitamin D?},
  series = {The Journal of Steroid Biochemistry and Molecular Biology},
  volume    = {180},
  journal   = {The Journal of Steroid Biochemistry and Molecular Biology},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0960-0760},
  doi       = {10.1016/j.jsbmb.2017.11.014},
  pages     = {87 -- 104},
  year      = {2018},
  abstract  = {Vitamin D, either in its D-2 or D-3 form, is essential for normal human development during intrauterine life, kidney function and bone health. Vitamin D deficiency has also been linked to cancer development and some auto immune diseases. Given this huge impact of vitamin Don human health, it is important for daily clinical practice and clinical research to have reliable tools to judge on the vitamin D status. The major circulating form of vitamin D is 25-hydroxyvitamin D (25(OH)D), although it is not the most active metabolite, the concentrations of total 25-hydroxyvitamin D in the serum are currently routinely used in clinical practice to assess vitamin D status. In the circulation, vitamin D - like other steroid hormones - is bound tightly to a special carrier - vitamin D-binding protein (DBP). Smaller amounts are bound to blood proteins - albumin and lipoproteins. Only very tiny amounts of the total vitamin D are free and potentially biologically active. Currently used vitamin D assays do not distinguish between the three forms of vitamin D - DBP-bound vitamin D, albumin-bound vitamin D and free, biologically active vitamin D. Diseases or conditions that affect the synthesis of DBP or albumin thus have a huge impact on the amount of circulating total vitamin D. DBP and albumin are synthesized in the liver, hence all patients with an impairment of liver function have alterations in their total vitamin D blood concentrations, while free vitamin D levels remain mostly constant. Sex steroids, in particular estrogens, stimulate the synthesis of DBP. This explains why total vitamin D concentrations are higher during pregnancy as compared to nonpregnant women, while the concentrations of free vitamin D remain similar in both groups of women. The vitamin D-DBP as well as vitamin D-albumin complexes are filtered through the glomeruli and re-uptaken by megalin in the proximal tubule. Therefore, all acute and chronic kidney diseases that are characterized by a tubular damage, are associated with a loss of vitamin D-DBP complexes in the urine. Finally, the gene encoding DBP protein is highly polymorphic in different human racial groups. In the current review, we will discuss how liver function, estrogens, kidney function and the genetic background might influence total circulating vitamin D levels and will discuss what vitamin D metabolite is more appropriate to measure under these conditions: free vitamin D or total vitamin D.},
  language  = {en}
}
@article{vonWebskyHasanReichetzederetal.2018,
  author    = {von Websky, Karoline and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Reichetzeder, Christoph and Tsuprykov, Oleg and Hocher, Berthold},
  title     = {Impact of vitamin D on pregnancy-related disorders and on offspring outcome},
  series = {The Journal of Steroid Biochemistry and Molecular Biology},
  volume    = {180},
  journal   = {The Journal of Steroid Biochemistry and Molecular Biology},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0960-0760},
  doi       = {10.1016/j.jsbmb.2017.11.008},
  pages     = {51 -- 64},
  year      = {2018},
  abstract  = {Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation. During pregnancy, adaptations in maternal vitamin D metabolism lead to a physiologic increase of vitamin D levels, mainly because of an increased renal production, although other potential sources like the placenta are being discussed. A sufficient supply of mother and child with calcium and vitamin D during pregnancy ensures a healthy bone development of the fetus, whereas lack of either of these nutrients can lead to the development of rickets in the child. Moreover, vitamin D insufficiency during pregnancy has consistently been associated with adverse maternal and neonatal pregnancy outcomes. In multitudinous studies, low maternal vitamin D status was associated with a higher risk for pre-eclampsia, gestational diabetes mellitus and other gestational diseases. Likewise, several negative consequences for the fetus have been reported, including fetal growth restriction, increased risk of preterm birth and a changed susceptibility for later-life diseases. However, study results are diverging and causality has not been proven so far. Meta-analyses on the relationship between maternal vitamin D status and pregnancy outcomes revealed a wide heterogeneity of studied populations and the applied methodology in vitamin D assessment. Until today, clinical guidelines for supplementation cannot be based on high-quality evidence and it is not clear if the required intake for pregnant women differs from non-pregnant women. Long-term safety data of vitamin D supplementation in pregnant women has not been established and overdosing of vitamin D might have unfavorable effects, especially in mothers and newborns with mutations of genes involved in vitamin D metabolism. Reliable data from large observational and interventional randomized control trials are urgently needed as a basis for any detailed and safe recommendations for supplementation in the general population and, most importantly, in pregnant women. This is of utmost importance, as ensuring a sufficient vitamin D-supply of mother and child implies a great potential for the prevention of birth complications and development of diseases.},
  language  = {en}
}
@article{LiLuTsuprykovetal.2018,
  author    = {Li, Jian and Lu, Yong-Ping and Tsuprykov, Oleg and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Reichetzeder, Christoph and Tian, Mei and Zhang, Xiao Li and Zhang, Qin and Sun, Guo-Ying and Guo, Jingli and Gaballa, Mohamed Mahmoud Salem Ahmed and Peng, Xiao-Ning and Lin, Ge and Hocher, Berthold},
  title     = {Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet},
  series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  volume    = {61},
  journal   = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  number    = {8},
  publisher = {Springer},
  address   = {New York},
  issn      = {0012-186X},
  doi       = {10.1007/s00125-018-4635-x},
  pages     = {1862 -- 1876},
  year      = {2018},
  abstract  = {Aims/hypothesis Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Methods Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy.},
  language  = {en}
}
@article{HasanvonWebskyReichetzederetal.2019,
  author    = {Hasan, Ahmed Abdallah Abdalrahman Mohamed and von Websky, Karoline and Reichetzeder, Christoph and Tsuprykov, Oleg and Gaballa, Mohamed Mahmoud Salem Ahmed and Guo, Jingli and Zeng, Shufei and Delic, Denis and Tammen, Harald and Klein, Thomas and Kleuser, Burkhard and Hocher, Berthold},
  title     = {Mechanisms of GLP-1 receptor-independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy},
  series = {Kidney international : official journal of the International Society of Nephrology},
  volume    = {95},
  journal   = {Kidney international : official journal of the International Society of Nephrology},
  number    = {6},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0085-2538},
  doi       = {10.1016/j.kint.2019.01.010},
  pages     = {1373 -- 1388},
  year      = {2019},
  abstract  = {Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway. Here we investigated the renal effects of the DPP-4 inhibitor linagliptin in Glp1r-/- knock out and wild-type mice with 5/6 nephrectomy (5/6Nx). Mice were allocated to groups: sham + wild type + placebo; 5/6Nx+ wild type + placebo; 5/6Nx+ wild type + linagliptin; sham + knock out+ placebo; 5/6Nx + knock out+ placebo; 5/6Nx + knock out+ linagliptin. 5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice. Two hundred ninety-eight proteomics signals were differentially regulated in kidneys among the groups, with 150 signals specific to linagliptin treatment as shown by mass spectrometry. Treatment significantly upregulated three peptides derived from collagen alpha-1(I), thymosin beta 4 and heterogeneous nuclear ribonucleoprotein Al (HNRNPA1) and significantly downregulated one peptide derived from Y box binding protein-1 (YB-1). The proteomics results were further confirmed using western blot and immunofluorescence microscopy. Also, 5/6Nx led to significant up-regulation of renal transforming growth factor-beta 1 and pSMAD3 expression in wild type mice and linagliptin significantly counteracted this up-regulation in wild type and GIplr-/- mice. Thus, the renoprotective effects of linagliptin cannot solely be attributed to the GLP-1/GLP1R pathway, highlighting the importance of other signaling pathways (collagen I homeostasis, HNRNPA1,YB-1,thymosin beta 4 and TGF-beta 1) influenced by DPP-4 inhibition.},
  language  = {en}
}
@inproceedings{TsuprykovBuseSkobloetal.2017,
  author    = {Tsuprykov, Oleg and Buse, Claudia and Skoblo, Roman and Hocher, Berthold},
  title     = {Free 25 (OH) vitamin D, but not total 25 (OH) vitamin D, is strongly correlated with gestational age and calcium in normal human pregnancy},
  series = {Journal of bone and mineral research},
  volume    = {32},
  booktitle = {Journal of bone and mineral research},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0884-0431},
  pages     = {S323 -- S323},
  year      = {2017},
  language  = {en}
}
@article{ReichetzederHeunischvonEinemetal.2017,
  author    = {Reichetzeder, Christoph and Heunisch, Fabian and von Einem, Gina-Franziska and Tsuprykov, Oleg and Kellner, Karl-Heinz and Dschietzig, Thomas and Kretschmer, Axel and Hocher, Berthold},
  title     = {Pre-interventional kynurenine predicts medium-term outcome after contrast media exposure due to coronary angiography},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft},
  volume    = {42},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000477222},
  pages     = {244 -- 256},
  year      = {2017},
  abstract  = {Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application. Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE. Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at >= 3.5 mu mol/L. Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine >= 3.5 mu mol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography.},
  language  = {en}
}
@misc{AlterOttvonWebskyetal.2011,
  author    = {Alter, Markus L. and Ott, Ina and von Websky, Karoline and Tsuprykov, Oleg and Sharkovska, Yuliya and Krause-Relle, Katharina and Raila, Jens and Henze, Andrea and Kretschmer, Axel and Stasch, Johannes-Peter and Hocher, Berthold},
  title     = {Additional stimulation of sGC on top of standard treatment with ARB`s may offer a new therapeutic approach for the treatment of diabetic nephropathy resistant to ARB treatment alone},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {855},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-42825},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-428250},
  pages     = {4},
  year      = {2011},
  abstract  = {Background Riociguat is the first of a new class of drugs, the soluble guanylate cyclase (sGC) stimulators. Riociguat has a dual mode of action: it sensitizes sGC to the body's own NO and can also increase sGC activity in the absence of NO. The NO-sGC-pathway is impaired in many cardiovascular diseases such as heart failure, pulmonary hypertension and diabetic nephropathy (DN). DN leads to high cardiovascular morbidity and mortality. There is still a high unmet medical need. The urinary albumin excretion rate is a predictive biomarker for these clinical events. Therefore, we investigated the effect of riociguat, alone and in combination with the angiotensin II receptor antagonist (ARB) telmisartan on the progression of DN in diabetic eNOS knock out mice, a new model closely resembling human pathology. Methods Seventy-six male eNOS knockout C57BL/6J mice were divided into 4 groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), riociguat (3 mg/kg), riociguat+telmisartan (3 and 1 mg/kg), and vehicle. Fourteen mice were used as non-diabetic controls. After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were highly increased and similar in all diabetic groups. Results Riociguat, alone (105.2 ± 2.5 mmHg; mean±SEM; n = 14) and in combination with telmisartan (105.0 ± 3.2 mmHg; n = 12), significantly reduced blood pressure versus diabetic controls (117.1 ± 2.2 mmHg; n = 14; p = 0.002 and p = 0.004, respectively), whereas telmisartan alone (111.2 ± 2.6 mmHg) showed a modest blood pressure lowering trend (p = 0.071; n = 14). The effects of single treatment with either riociguat (97.1 ± 15.7 µg/d; n = 13) or telmisartan (97.8 ± 26.4 µg/d; n = 14) did not significantly lower albumin excretion on its own (p = 0.067 and p = 0.101, respectively). However, the combined treatment led to significantly lower urinary albumin excretion (47.3 ± 9.6 µg/d; n = 12) compared to diabetic controls (170.8 ± 34.2 µg/d; n = 13; p = 0.004), and reached levels similar to non-diabetic controls (31.4 ± 10.1 µg/d, n = 12). Conclusion Riociguat significantly reduced urinary albumin excretion in diabetic eNOS knock out mice that were refractory to treatment with ARB's alone. Patients with diabetic nephropathy refractory to treatment with ARB's have the worst prognosis among all patients with diabetic nephropathy. Our data indicate that additional stimulation of sGC on top of standard treatment with ARB`s may offer a new therapeutic approach for patients with diabetic nephropathy resistant to ARB treatment.},
  language  = {en}
}
@article{HocherHaumannRahnenfuehreretal.2016,
  author    = {Hocher, Berthold and Haumann, Hannah and Rahnenf{\"u}hrer, Jan and Reichetzeder, Christoph and Kalk, Philipp and Pfab, Thiemo and Tsuprykov, Oleg and Winter, Stefan and Hofmann, Ute and Li, Jian and P{\"u}schel, Gerhard Paul and Lang, Florian and Schuppan, Detlef and Schwab, Matthias and Schaeffeler, Elke},
  title     = {Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner},
  series = {Epigenetics : the official journal of the DNA Methylation Society},
  volume    = {11},
  journal   = {Epigenetics : the official journal of the DNA Methylation Society},
  publisher = {Routledge, Taylor \& Francis Group},
  address   = {Philadelphia},
  issn      = {1559-2294},
  doi       = {10.1080/15592294.2016.1184800},
  pages     = {539 -- 552},
  year      = {2016},
  abstract  = {Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.},
  language  = {en}
}