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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/109182

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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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