Rodent models of diabetic kidney disease: human translatability and preclinical validity

Frederikke E Sembach; Mette V Østergaard; Niels Vrang; Bo Feldt-Rasmussen; Keld Fosgerau; Jacob Jelsing; Lisbeth N Fink

doi:10.1016/j.drudis.2020.05.004

Rodent models of diabetic kidney disease: human translatability and preclinical validity

Frederikke E Sembach, Mette V Østergaard, Niels Vrang, Bo Feldt-Rasmussen, Keld Fosgerau, Jacob Jelsing, Lisbeth N Fink

8 Citationer (Scopus)

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Except for SGLT2 inhibitors and GLP-1R agonists, there have been few changes in DKD treatment over the past 25 years, when multifactorial intervention was introduced in patients with type 2 diabetes mellitus (T2DM). The unmet clinical need is partly due to the lack of animal models that replicate clinical features of human DKD, which has raised concern about the utility of these models in preclinical drug discovery. In this review, we performed a comprehensive analysis of rodent models of DKD to compare treatment efficacy from preclinical testing with outcome from clinical trials. We also investigated whether rodent models are predictive for clinical outcomes of therapeutic agents in human DKD.

Originalsprog	Engelsk
Tidsskrift	Drug Discovery Today
Vol/bind	26
Udgave nummer	1
Sider (fra-til)	200-217
Antal sider	18
ISSN	1359-6446
DOI	https://doi.org/10.1016/j.drudis.2020.05.004
Status	Udgivet - jan. 2021

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10.1016/j.drudis.2020.05.004

Citationsformater

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title = "Rodent models of diabetic kidney disease: human translatability and preclinical validity",

abstract = "Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Except for SGLT2 inhibitors and GLP-1R agonists, there have been few changes in DKD treatment over the past 25 years, when multifactorial intervention was introduced in patients with type 2 diabetes mellitus (T2DM). The unmet clinical need is partly due to the lack of animal models that replicate clinical features of human DKD, which has raised concern about the utility of these models in preclinical drug discovery. In this review, we performed a comprehensive analysis of rodent models of DKD to compare treatment efficacy from preclinical testing with outcome from clinical trials. We also investigated whether rodent models are predictive for clinical outcomes of therapeutic agents in human DKD.",

author = "Sembach, {Frederikke E} and {\O}stergaard, {Mette V} and Niels Vrang and Bo Feldt-Rasmussen and Keld Fosgerau and Jacob Jelsing and Fink, {Lisbeth N}",

year = "2021",

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doi = "10.1016/j.drudis.2020.05.004",

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TY - JOUR

T1 - Rodent models of diabetic kidney disease

T2 - human translatability and preclinical validity

AU - Sembach, Frederikke E

AU - Østergaard, Mette V

AU - Vrang, Niels

AU - Feldt-Rasmussen, Bo

AU - Fosgerau, Keld

AU - Jelsing, Jacob

AU - Fink, Lisbeth N

PY - 2021/1

Y1 - 2021/1

N2 - Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Except for SGLT2 inhibitors and GLP-1R agonists, there have been few changes in DKD treatment over the past 25 years, when multifactorial intervention was introduced in patients with type 2 diabetes mellitus (T2DM). The unmet clinical need is partly due to the lack of animal models that replicate clinical features of human DKD, which has raised concern about the utility of these models in preclinical drug discovery. In this review, we performed a comprehensive analysis of rodent models of DKD to compare treatment efficacy from preclinical testing with outcome from clinical trials. We also investigated whether rodent models are predictive for clinical outcomes of therapeutic agents in human DKD.

AB - Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Except for SGLT2 inhibitors and GLP-1R agonists, there have been few changes in DKD treatment over the past 25 years, when multifactorial intervention was introduced in patients with type 2 diabetes mellitus (T2DM). The unmet clinical need is partly due to the lack of animal models that replicate clinical features of human DKD, which has raised concern about the utility of these models in preclinical drug discovery. In this review, we performed a comprehensive analysis of rodent models of DKD to compare treatment efficacy from preclinical testing with outcome from clinical trials. We also investigated whether rodent models are predictive for clinical outcomes of therapeutic agents in human DKD.

U2 - 10.1016/j.drudis.2020.05.004

DO - 10.1016/j.drudis.2020.05.004

M3 - Review

C2 - 32413492

SN - 1359-6446

VL - 26

SP - 200

EP - 217

JO - Drug Discovery Today

JF - Drug Discovery Today

IS - 1

ER -

Rodent models of diabetic kidney disease: human translatability and preclinical validity

Abstract

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