Urinary renin in patients and mice with diabetic kidney disease
- Autores
- Tang, Jeannette; Wysocki, Jan; Ye, Minghao; Garramuño, Patricia; Rein, Johannes; Shirazi, Mina; Bader, Michael; Gomez, Roberto Ariel; Sequeira Lopez, Maria Luisa S.; Afkarian, Maryam; Batlle, Daniel
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- In patients with diabetic kidney disease (DKD), plasma renin activity is usually decreased, but there is limited information on urinary renin and its origin. Urinary renin was evaluated in samples from patients with longstanding type I diabetes mellitus and mice with streptozotocin-induced diabetes mellitus. Renin-reporter mouse model (Ren1d-Cre;mT/ mG) was made diabetic with streptozotocin to examine whether the distribution of cells of the renin lineage was altered in a chronic diabetic environment. Active renin was increased in urine samples from patients with DKD (n=36), compared with those without DKD (n=38; 3.2 versus 1.3 pg/mg creatinine; P<0.001). In mice with streptozotocin-induced diabetes mellitus, urine renin was also increased compared with nondiabetic controls. By immunohistochemistry, in mice with streptozotocin-induced diabetes mellitus, juxtaglomerular apparatus and proximal tubular renin staining were reduced, whereas collecting tubule staining, by contrast, was increased. To examine the role of filtration and tubular reabsorption on urinary renin, mice were either infused with either mouse or human recombinant renin and lysine (a blocker of proximal tubular protein reabsorption). Infusion of either form of renin together with lysine markedly increased urinary renin such that it was no longer different between nondiabetic and diabetic mice. Megalin mRNA was reduced in the kidney cortex of streptozotocin-treated mice (0.70±0.09 versus 1.01±0.04 in controls, P=0.01) consistent with impaired tubular reabsorption. In Ren1d-Cre;mT/mG with streptozotocin-induced diabetes mellitus, the distribution of renin lineage cells within the kidney was similar to nondiabetic renin-reporter mice. No evidence for migration of cells of renin linage to the collecting duct in diabetic mice could be found. Renin mRNA in microdissected collecting ducts from streptozotocin-treated mice, moreover, was not significantly different than in controls, whereas in kidney cortex, largely reflecting juxtaglomerular apparatus renin, it was significantly reduced. In conclusion, in urine from patients with type 1 diabetes mellitus and DKD and from mice with streptozotocin-induced diabetes mellitus, renin is elevated. This cannot be attributed to production from cells of the renin lineage migrating to the collecting duct in a chronic hyperglycemic environment. Rather, the elevated levels of urinary renin found in DKD are best attributed to altered glomerular filteration and impaired proximal tubular reabsorption.
Fil: Tang, Jeannette. Northwestern University; Estados Unidos
Fil: Wysocki, Jan. Northwestern University; Estados Unidos
Fil: Ye, Minghao. Northwestern University; Estados Unidos
Fil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Rein, Johannes. Northwestern University; Estados Unidos
Fil: Shirazi, Mina. Northwestern University; Estados Unidos
Fil: Bader, Michael. Charité Universitätsmedizin; Alemania
Fil: Gomez, Roberto Ariel. University of Virginia; Estados Unidos
Fil: Sequeira Lopez, Maria Luisa S.. University of Virginia; Estados Unidos
Fil: Afkarian, Maryam. University of California at Davis; Estados Unidos
Fil: Batlle, Daniel. Northwestern University; Estados Unidos - Materia
-
diabetes mellitus
kidney
mice
renin
renin-angiotensin system - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/109182
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Urinary renin in patients and mice with diabetic kidney diseaseTang, JeannetteWysocki, JanYe, MinghaoGarramuño, PatriciaRein, JohannesShirazi, MinaBader, MichaelGomez, Roberto ArielSequeira Lopez, Maria Luisa S.Afkarian, MaryamBatlle, Danieldiabetes mellituskidneymicereninrenin-angiotensin systemhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In patients with diabetic kidney disease (DKD), plasma renin activity is usually decreased, but there is limited information on urinary renin and its origin. Urinary renin was evaluated in samples from patients with longstanding type I diabetes mellitus and mice with streptozotocin-induced diabetes mellitus. Renin-reporter mouse model (Ren1d-Cre;mT/ mG) was made diabetic with streptozotocin to examine whether the distribution of cells of the renin lineage was altered in a chronic diabetic environment. Active renin was increased in urine samples from patients with DKD (n=36), compared with those without DKD (n=38; 3.2 versus 1.3 pg/mg creatinine; P<0.001). In mice with streptozotocin-induced diabetes mellitus, urine renin was also increased compared with nondiabetic controls. By immunohistochemistry, in mice with streptozotocin-induced diabetes mellitus, juxtaglomerular apparatus and proximal tubular renin staining were reduced, whereas collecting tubule staining, by contrast, was increased. To examine the role of filtration and tubular reabsorption on urinary renin, mice were either infused with either mouse or human recombinant renin and lysine (a blocker of proximal tubular protein reabsorption). Infusion of either form of renin together with lysine markedly increased urinary renin such that it was no longer different between nondiabetic and diabetic mice. Megalin mRNA was reduced in the kidney cortex of streptozotocin-treated mice (0.70±0.09 versus 1.01±0.04 in controls, P=0.01) consistent with impaired tubular reabsorption. In Ren1d-Cre;mT/mG with streptozotocin-induced diabetes mellitus, the distribution of renin lineage cells within the kidney was similar to nondiabetic renin-reporter mice. No evidence for migration of cells of renin linage to the collecting duct in diabetic mice could be found. Renin mRNA in microdissected collecting ducts from streptozotocin-treated mice, moreover, was not significantly different than in controls, whereas in kidney cortex, largely reflecting juxtaglomerular apparatus renin, it was significantly reduced. In conclusion, in urine from patients with type 1 diabetes mellitus and DKD and from mice with streptozotocin-induced diabetes mellitus, renin is elevated. This cannot be attributed to production from cells of the renin lineage migrating to the collecting duct in a chronic hyperglycemic environment. Rather, the elevated levels of urinary renin found in DKD are best attributed to altered glomerular filteration and impaired proximal tubular reabsorption.Fil: Tang, Jeannette. Northwestern University; Estados UnidosFil: Wysocki, Jan. Northwestern University; Estados UnidosFil: Ye, Minghao. Northwestern University; Estados UnidosFil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Rein, Johannes. Northwestern University; Estados UnidosFil: Shirazi, Mina. Northwestern University; Estados UnidosFil: Bader, Michael. Charité Universitätsmedizin; AlemaniaFil: Gomez, Roberto Ariel. University of Virginia; Estados UnidosFil: Sequeira Lopez, Maria Luisa S.. University of Virginia; Estados UnidosFil: Afkarian, Maryam. University of California at Davis; Estados UnidosFil: Batlle, Daniel. Northwestern University; Estados UnidosLippincott Williams2019-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/109182Tang, Jeannette; Wysocki, Jan; Ye, Minghao; Garramuño, Patricia; Rein, Johannes; et al.; Urinary renin in patients and mice with diabetic kidney disease; Lippincott Williams; Hypertension; 74; 1; 7-2019; 83-940194-911XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.119.12873info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.12873info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:35Zoai:ri.conicet.gov.ar:11336/109182instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:02:36.164CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Urinary renin in patients and mice with diabetic kidney disease |
title |
Urinary renin in patients and mice with diabetic kidney disease |
spellingShingle |
Urinary renin in patients and mice with diabetic kidney disease Tang, Jeannette diabetes mellitus kidney mice renin renin-angiotensin system |
title_short |
Urinary renin in patients and mice with diabetic kidney disease |
title_full |
Urinary renin in patients and mice with diabetic kidney disease |
title_fullStr |
Urinary renin in patients and mice with diabetic kidney disease |
title_full_unstemmed |
Urinary renin in patients and mice with diabetic kidney disease |
title_sort |
Urinary renin in patients and mice with diabetic kidney disease |
dc.creator.none.fl_str_mv |
Tang, Jeannette Wysocki, Jan Ye, Minghao Garramuño, Patricia Rein, Johannes Shirazi, Mina Bader, Michael Gomez, Roberto Ariel Sequeira Lopez, Maria Luisa S. Afkarian, Maryam Batlle, Daniel |
author |
Tang, Jeannette |
author_facet |
Tang, Jeannette Wysocki, Jan Ye, Minghao Garramuño, Patricia Rein, Johannes Shirazi, Mina Bader, Michael Gomez, Roberto Ariel Sequeira Lopez, Maria Luisa S. Afkarian, Maryam Batlle, Daniel |
author_role |
author |
author2 |
Wysocki, Jan Ye, Minghao Garramuño, Patricia Rein, Johannes Shirazi, Mina Bader, Michael Gomez, Roberto Ariel Sequeira Lopez, Maria Luisa S. Afkarian, Maryam Batlle, Daniel |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
diabetes mellitus kidney mice renin renin-angiotensin system |
topic |
diabetes mellitus kidney mice renin renin-angiotensin system |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
In patients with diabetic kidney disease (DKD), plasma renin activity is usually decreased, but there is limited information on urinary renin and its origin. Urinary renin was evaluated in samples from patients with longstanding type I diabetes mellitus and mice with streptozotocin-induced diabetes mellitus. Renin-reporter mouse model (Ren1d-Cre;mT/ mG) was made diabetic with streptozotocin to examine whether the distribution of cells of the renin lineage was altered in a chronic diabetic environment. Active renin was increased in urine samples from patients with DKD (n=36), compared with those without DKD (n=38; 3.2 versus 1.3 pg/mg creatinine; P<0.001). In mice with streptozotocin-induced diabetes mellitus, urine renin was also increased compared with nondiabetic controls. By immunohistochemistry, in mice with streptozotocin-induced diabetes mellitus, juxtaglomerular apparatus and proximal tubular renin staining were reduced, whereas collecting tubule staining, by contrast, was increased. To examine the role of filtration and tubular reabsorption on urinary renin, mice were either infused with either mouse or human recombinant renin and lysine (a blocker of proximal tubular protein reabsorption). Infusion of either form of renin together with lysine markedly increased urinary renin such that it was no longer different between nondiabetic and diabetic mice. Megalin mRNA was reduced in the kidney cortex of streptozotocin-treated mice (0.70±0.09 versus 1.01±0.04 in controls, P=0.01) consistent with impaired tubular reabsorption. In Ren1d-Cre;mT/mG with streptozotocin-induced diabetes mellitus, the distribution of renin lineage cells within the kidney was similar to nondiabetic renin-reporter mice. No evidence for migration of cells of renin linage to the collecting duct in diabetic mice could be found. Renin mRNA in microdissected collecting ducts from streptozotocin-treated mice, moreover, was not significantly different than in controls, whereas in kidney cortex, largely reflecting juxtaglomerular apparatus renin, it was significantly reduced. In conclusion, in urine from patients with type 1 diabetes mellitus and DKD and from mice with streptozotocin-induced diabetes mellitus, renin is elevated. This cannot be attributed to production from cells of the renin lineage migrating to the collecting duct in a chronic hyperglycemic environment. Rather, the elevated levels of urinary renin found in DKD are best attributed to altered glomerular filteration and impaired proximal tubular reabsorption. Fil: Tang, Jeannette. Northwestern University; Estados Unidos Fil: Wysocki, Jan. Northwestern University; Estados Unidos Fil: Ye, Minghao. Northwestern University; Estados Unidos Fil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Rein, Johannes. Northwestern University; Estados Unidos Fil: Shirazi, Mina. Northwestern University; Estados Unidos Fil: Bader, Michael. Charité Universitätsmedizin; Alemania Fil: Gomez, Roberto Ariel. University of Virginia; Estados Unidos Fil: Sequeira Lopez, Maria Luisa S.. University of Virginia; Estados Unidos Fil: Afkarian, Maryam. University of California at Davis; Estados Unidos Fil: Batlle, Daniel. Northwestern University; Estados Unidos |
description |
In patients with diabetic kidney disease (DKD), plasma renin activity is usually decreased, but there is limited information on urinary renin and its origin. Urinary renin was evaluated in samples from patients with longstanding type I diabetes mellitus and mice with streptozotocin-induced diabetes mellitus. Renin-reporter mouse model (Ren1d-Cre;mT/ mG) was made diabetic with streptozotocin to examine whether the distribution of cells of the renin lineage was altered in a chronic diabetic environment. Active renin was increased in urine samples from patients with DKD (n=36), compared with those without DKD (n=38; 3.2 versus 1.3 pg/mg creatinine; P<0.001). In mice with streptozotocin-induced diabetes mellitus, urine renin was also increased compared with nondiabetic controls. By immunohistochemistry, in mice with streptozotocin-induced diabetes mellitus, juxtaglomerular apparatus and proximal tubular renin staining were reduced, whereas collecting tubule staining, by contrast, was increased. To examine the role of filtration and tubular reabsorption on urinary renin, mice were either infused with either mouse or human recombinant renin and lysine (a blocker of proximal tubular protein reabsorption). Infusion of either form of renin together with lysine markedly increased urinary renin such that it was no longer different between nondiabetic and diabetic mice. Megalin mRNA was reduced in the kidney cortex of streptozotocin-treated mice (0.70±0.09 versus 1.01±0.04 in controls, P=0.01) consistent with impaired tubular reabsorption. In Ren1d-Cre;mT/mG with streptozotocin-induced diabetes mellitus, the distribution of renin lineage cells within the kidney was similar to nondiabetic renin-reporter mice. No evidence for migration of cells of renin linage to the collecting duct in diabetic mice could be found. Renin mRNA in microdissected collecting ducts from streptozotocin-treated mice, moreover, was not significantly different than in controls, whereas in kidney cortex, largely reflecting juxtaglomerular apparatus renin, it was significantly reduced. In conclusion, in urine from patients with type 1 diabetes mellitus and DKD and from mice with streptozotocin-induced diabetes mellitus, renin is elevated. This cannot be attributed to production from cells of the renin lineage migrating to the collecting duct in a chronic hyperglycemic environment. Rather, the elevated levels of urinary renin found in DKD are best attributed to altered glomerular filteration and impaired proximal tubular reabsorption. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-07 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/109182 Tang, Jeannette; Wysocki, Jan; Ye, Minghao; Garramuño, Patricia; Rein, Johannes; et al.; Urinary renin in patients and mice with diabetic kidney disease; Lippincott Williams; Hypertension; 74; 1; 7-2019; 83-94 0194-911X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/109182 |
identifier_str_mv |
Tang, Jeannette; Wysocki, Jan; Ye, Minghao; Garramuño, Patricia; Rein, Johannes; et al.; Urinary renin in patients and mice with diabetic kidney disease; Lippincott Williams; Hypertension; 74; 1; 7-2019; 83-94 0194-911X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.119.12873 info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.12873 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Lippincott Williams |
publisher.none.fl_str_mv |
Lippincott Williams |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269765652971520 |
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13.13397 |