A Quantitative Systems Pharmacology Kidney Model of Diabetes Associated Renal Hyperfiltration and the Effects of SGLT Inhibitors
Open accessAbstract
The early stage of diabetes mellitus is characterized by increased glomerular filtration rate (GFR), known as hyperfiltration, which is believed to be one of the main causes leading to renal injury in diabetes. Sodium‐glucose cotransporter 2 inhibitors (SGLT 2i) have been shown to be able to reverse hyperfiltration in some patients. We developed a mechanistic computational model of the kidney that explains the interplay of hyperglycemia and hyperfiltration and integrates the pharmacokinetics/pharmacodynamics (PK/PD) of the SGLT 2i dapagliflozin. Based on simulation results, we propose kidney growth as the necessary process for hyperfiltration progression. Further, the model indicates that renal SGLT 1i could significantly improve hyperfiltration when added to SGTL 2i. Integrated into a physiologically based PK/PD (PBPK/PD) Diabetes Platform, the model presents a powerful tool for aiding drug development, prediction of hyperfiltration risk, and allows the assessment of the outcomes of individualized treatments with SGLT 1‐inhibitors and SGLT 2‐inhibitors and their co‐administration with insulin.
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References 43 · Cited by 19
Research works printed but not linked: 1
- [42]Pape, H.‐C., Kurtz, A. & Silbernagl, S. Physiologie (Georg Thieme Verlag, Stuttgart, New York, NY, 2010).
- Authors
- Balazki, P., Schaller, S., Eissing, T., & Lehr, T.
- Affiliations
- Bayer (Germany) (DE)
- esqLABS GmbH Saterland Germany
- Saarland University (DE)
- Corresponding author
- Lehr, Thorsten
- Venue
- CPT: Pharmacometrics & Systems Pharmacology
- Publisher
- Wiley
- Published
- 2018-10-22
- Volume
- 7
- Issue
- 12
- Pages
- 788-797
- ISSN
- 2163-8306 (ISSN-L)
- PMC
- PMC6310870
- OpenAlex
- W2895101793
- Cited by
- 19
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 3
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Publications of the UdS (Saarland University)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- SGLT2 inhibitors, dapagliflozin, SGLT1 inhibitors, kidney growth, glomerular filtration rate, hyperglycemia
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Humans, Kidney Diseases, Models, Biological
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