{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:51137"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:51137","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Der therapeutische Effekt von Calcimimetika auf die Progression extraossärer Kalzifikation und ossärer Dekalzifikation bei Ahsg/Fetuin-A-defizienten Mäusen","abstract":"Rising incidence and prevalence of chronic kidney disease during the last few years lead to replacement of organ function in the long run and dependency on regular dialysis for an increasing number of people. This fact is associated with an augmentation of complications entailed by terminal renal failure which go along with a considerable elevation of cardiovascular morbidity and mortality. Extraosseous calcifications seem to have an adverse meaning in this context. Not only vessels but also organs and soft tissue are common sites of massive calcification whereas degradation of calcium carbonate is seen throughout the skeleton leading to renal osteopathy. Especially secondary hyperparathyroidism plays an important role in this multifactorial pathogenesis and served as starting point of medicamentous intervention in our experimental set-up. Via application of calcimimetics the goal of reducing levels of parathyroid hormone as well as calcium phosphate product can be achieved more frequently. The fetuin-knockout mouse model represents a patient suffering from chronic renal failure and its resulting consequences which made it possible to analyse additional effects of the latest calcimimetic agent R-641. The potency of the new compound was consistent with all precursor substances revealing an improved pharmacokinetic profile. There was no clue for any so far unknown adverse drug reactions. In lungs, kidneys and liver a significant influence on tissue calcification compared to vehicle-treated groups could not be detected. However, hearts of verum-treated mice showed a noticeably lower content of calcium. At the gene expression level of osteoblast transdifferentiation R-641 lead to a reduction of osteopontin and an increase of matrix-gla-protein – still without statistic significance. In samples of aortic tissue a significant reduction of cbfa-1 and downstream osteopontin could be attained. Therefore a protective effect on the cardiovascular system can be assumed. Concerning renal osteopathy calcimimetic treatment induced a considerably lower implementation of connective tissue into the bone. Besides typical parameters of osteomalacia such as osteoid surface and osteoid volume could be reduced down to normal values. In contrast osteoid thickness and osteoclast surface remained unchanged. So R-641 causes basically a decline of osteitis fibrosa signs among the knockouts. In summary calcimimetics represent a promising class of active components whose further positive effects are probably still to be discovered. They might be integrated in the standard therapeutic regime of terminal renal insufficiency in the future which could reduce cardiovascular risk factors as well as negative side effects of present therapeutic schemes and possibly improve long time survival of dialysis patients.","abstract_html":"Rising incidence and prevalence of chronic kidney disease during the last few years lead to replacement of organ function in the long run and dependency on regular dialysis for an increasing number of people. This fact is associated with an augmentation of complications entailed by terminal renal failure which go along with a considerable elevation of cardiovascular morbidity and mortality. Extraosseous calcifications seem to have an adverse meaning in this context. Not only vessels but also organs and soft tissue are common sites of massive calcification whereas degradation of calcium carbonate is seen throughout the skeleton leading to renal osteopathy. Especially secondary hyperparathyroidism plays an important role in this multifactorial pathogenesis and served as starting point of medicamentous intervention in our experimental set-up. Via application of calcimimetics the goal of reducing levels of parathyroid hormone as well as calcium phosphate product can be achieved more frequently. The fetuin-knockout mouse model represents a patient suffering from chronic renal failure and its resulting consequences which made it possible to analyse additional effects of the latest calcimimetic agent R-641. The potency of the new compound was consistent with all precursor substances revealing an improved pharmacokinetic profile. There was no clue for any so far unknown adverse drug reactions. In lungs, kidneys and liver a significant influence on tissue calcification compared to vehicle-treated groups could not be detected. However, hearts of verum-treated mice showed a noticeably lower content of calcium. At the gene expression level of osteoblast transdifferentiation R-641 lead to a reduction of osteopontin and an increase of matrix-gla-protein – still without statistic significance. In samples of aortic tissue a significant reduction of cbfa-1 and downstream osteopontin could be attained. Therefore a protective effect on the cardiovascular system can be assumed. Concerning renal osteopathy calcimimetic treatment induced a considerably lower implementation of connective tissue into the bone. Besides typical parameters of osteomalacia such as osteoid surface and osteoid volume could be reduced down to normal values. In contrast osteoid thickness and osteoclast surface remained unchanged. So R-641 causes basically a decline of osteitis fibrosa signs among the knockouts. In summary calcimimetics represent a promising class of active components whose further positive effects are probably still to be discovered. They might be integrated in the standard therapeutic regime of terminal renal insufficiency in the future which could reduce cardiovascular risk factors as well as negative side effects of present therapeutic schemes and possibly improve long time survival of dialysis patients.","abstract_has_math":false,"creators":["Göbner, Sonja"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Jahnen-Dechent, Wilhelm"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-30T19:40:33Z","subjects":["info:eu-repo/classification/ddc/610","Dialyse","Chronische Niereninsuffizienz","Sekundärer Hyperparathyreoidismus","Fetoprotein <alpha->","Verkalkung","Renale Osteopathie","Parathormon","Calcium","Aorta","Vitamin-D-Mangel","Medizin","Kalzimimetika","Calcium-Phosphat-Produkt","akzelerierte Arteriosklerose","Mönckeberg-Sklerose","Calcimimetics","calcium-phosphate-product","accelerated arteriosclerosis","moenckeberg s sclerosis"],"languages":["ger"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113452%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113452%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113452%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/51137","outbound_label":"Repository record","outbound_source":"dc:identifier"},"source_record":{"url":"https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51137","prefix":"oai_dc"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jahnen-Dechent, Wilhelm"]},{"key":"dc:creator","label":"Author","values":["Göbner, Sonja"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2009"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-28154"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Dialyse","Chronische Niereninsuffizienz","Sekundärer Hyperparathyreoidismus","Fetoprotein <alpha->","Verkalkung","Renale Osteopathie","Parathormon","Calcium","Aorta","Vitamin-D-Mangel","Medizin","Kalzimimetika","Calcium-Phosphat-Produkt","akzelerierte Arteriosklerose","Mönckeberg-Sklerose","Calcimimetics","calcium-phosphate-product","accelerated arteriosclerosis","moenckeberg s sclerosis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["ger"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/51137","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113452%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Rising incidence and prevalence of chronic kidney disease during the last few years lead to replacement of organ function in the long run and dependency on regular dialysis for an increasing number of people. This fact is associated with an augmentation of complications entailed by terminal renal failure which go along with a considerable elevation of cardiovascular morbidity and mortality. Extraosseous calcifications seem to have an adverse meaning in this context. Not only vessels but also organs and soft tissue are common sites of massive calcification whereas degradation of calcium carbonate is seen throughout the skeleton leading to renal osteopathy. Especially secondary hyperparathyroidism plays an important role in this multifactorial pathogenesis and served as starting point of medicamentous intervention in our experimental set-up. Via application of calcimimetics the goal of reducing levels of parathyroid hormone as well as calcium phosphate product can be achieved more frequently. The fetuin-knockout mouse model represents a patient suffering from chronic renal failure and its resulting consequences which made it possible to analyse additional effects of the latest calcimimetic agent R-641. The potency of the new compound was consistent with all precursor substances revealing an improved pharmacokinetic profile. There was no clue for any so far unknown adverse drug reactions. In lungs, kidneys and liver a significant influence on tissue calcification compared to vehicle-treated groups could not be detected. However, hearts of verum-treated mice showed a noticeably lower content of calcium. At the gene expression level of osteoblast transdifferentiation R-641 lead to a reduction of osteopontin and an increase of matrix-gla-protein – still without statistic significance. In samples of aortic tissue a significant reduction of cbfa-1 and downstream osteopontin could be attained. Therefore a protective effect on the cardiovascular system can be assumed. Concerning renal osteopathy calcimimetic treatment induced a considerably lower implementation of connective tissue into the bone. Besides typical parameters of osteomalacia such as osteoid surface and osteoid volume could be reduced down to normal values. In contrast osteoid thickness and osteoclast surface remained unchanged. So R-641 causes basically a decline of osteitis fibrosa signs among the knockouts. In summary calcimimetics represent a promising class of active components whose further positive effects are probably still to be discovered. They might be integrated in the standard therapeutic regime of terminal renal insufficiency in the future which could reduce cardiovascular risk factors as well as negative side effects of present therapeutic schemes and possibly improve long time survival of dialysis patients."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University V, 72 S. : Ill., graph. Darst. (2009). = Aachen, Techn. Hochsch., Diss., 2009"]},{"key":"dc:title","label":"Title","values":["Der therapeutische Effekt von Calcimimetika auf die Progression extraossärer Kalzifikation und ossärer Dekalzifikation bei Ahsg/Fetuin-A-defizienten Mäusen"]}]}],"canonical_facts":{"dc:contributor":["Jahnen-Dechent, Wilhelm"],"dc:coverage":["DE"],"dc:creator":["Göbner, Sonja"],"dc:date":["2009"],"dc:description":["Rising incidence and prevalence of chronic kidney disease during the last few years lead to replacement of organ function in the long run and dependency on regular dialysis for an increasing number of people. This fact is associated with an augmentation of complications entailed by terminal renal failure which go along with a considerable elevation of cardiovascular morbidity and mortality. Extraosseous calcifications seem to have an adverse meaning in this context. Not only vessels but also organs and soft tissue are common sites of massive calcification whereas degradation of calcium carbonate is seen throughout the skeleton leading to renal osteopathy. Especially secondary hyperparathyroidism plays an important role in this multifactorial pathogenesis and served as starting point of medicamentous intervention in our experimental set-up. Via application of calcimimetics the goal of reducing levels of parathyroid hormone as well as calcium phosphate product can be achieved more frequently. The fetuin-knockout mouse model represents a patient suffering from chronic renal failure and its resulting consequences which made it possible to analyse additional effects of the latest calcimimetic agent R-641. The potency of the new compound was consistent with all precursor substances revealing an improved pharmacokinetic profile. There was no clue for any so far unknown adverse drug reactions. In lungs, kidneys and liver a significant influence on tissue calcification compared to vehicle-treated groups could not be detected. However, hearts of verum-treated mice showed a noticeably lower content of calcium. At the gene expression level of osteoblast transdifferentiation R-641 lead to a reduction of osteopontin and an increase of matrix-gla-protein – still without statistic significance. In samples of aortic tissue a significant reduction of cbfa-1 and downstream osteopontin could be attained. Therefore a protective effect on the cardiovascular system can be assumed. Concerning renal osteopathy calcimimetic treatment induced a considerably lower implementation of connective tissue into the bone. Besides typical parameters of osteomalacia such as osteoid surface and osteoid volume could be reduced down to normal values. In contrast osteoid thickness and osteoclast surface remained unchanged. So R-641 causes basically a decline of osteitis fibrosa signs among the knockouts. In summary calcimimetics represent a promising class of active components whose further positive effects are probably still to be discovered. They might be integrated in the standard therapeutic regime of terminal renal insufficiency in the future which could reduce cardiovascular risk factors as well as negative side effects of present therapeutic schemes and possibly improve long time survival of dialysis patients."],"dc:identifier":["https://publications.rwth-aachen.de/record/51137","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113452%22"],"dc:language":["ger"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-28154"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University V, 72 S. : Ill., graph. Darst. (2009). = Aachen, Techn. 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