The DOI matches its Crossref record; 119 of the 120 references it cites were found in a registry or an index.
The role of renal hypoxia in the pathogenesis of diabetic kidney disease: a promising target for newer renoprotective agents including SGLT2 inhibitors?
Open accessAbstract
Diabetic kidney disease is the most common cause of end-stage kidney disease and poses a major global health problem. Finding new, safe, and effective strategies to halt this disease has proven to be challenging. In part that is because the underlying mechanisms are complex and not fully understood. However, in recent years, evidence has accumulated suggesting that chronic hypoxia may be the primary pathophysiological pathway driving diabetic kidney disease and chronic kidney disease of other etiologies and was called the chronic hypoxia hypothesis. Hypoxia is the result of a mismatch between oxygen delivery and oxygen demand. The primary determinant of oxygen delivery is renal perfusion (blood flow per tissue mass), whereas the main driver of oxygen demand is active sodium reabsorption. Diabetes mellitus is thought to compromise the oxygen balance by impairing oxygen delivery owing to hyperglycemia-associated microvascular damage and exacerbate oxygen demand owing to increased sodium reabsorption as a result of sodium-glucose cotransporter upregulation and glomerular hyperfiltration. The resultant hypoxic injury creates a vicious cycle of capillary damage, inflammation, deposition of the extracellular matrix, and, ultimately, fibrosis and nephron loss. This review will frame the role of chronic hypoxia in the pathogenesis of diabetic kidney disease and its prospect as a promising therapeutic target. We will outline the cellular mechanisms of hypoxia and evidence for renal hypoxia in animal and human studies. In addition, we will highlight the promise of newer imaging modalities including blood oxygenation level-dependent magnetic resonance imaging and discuss salutary interventions such as sodium-glucose cotransporter 2 inhibition that (may) protect the kidney through amelioration of renal hypoxia.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“First, it may be due to impaired oxygen delivery resulting from microvascular damage. Second, increased oxygen consumption, caused by both glomerular hyperfiltration and inefficient energy generation due to impaired insulin sensitivity, may also contribute (38).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811744 · Cited by 6,189
Zelniker, T. A., Wiviott, S. D., Raz, I., Im, K., Goodrich, E. L., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Furtado, R. H. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32590-x · Cited by 2,845
Cherney, D. Z. I., Perkins, B. A., Soleymanlou, N., Maione, M., Lai, V., Lee, A., Fagan, N. M., Woerle, H. J., Johansen, O. E., Broedl, U. C., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.005081 · Cited by 1,329
Chronic Hypoxia and Tubulointerstitial Injury
Nangaku, M. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005070757 · Cited by 1,146
Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease
de Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M. P., Christ‐Schmidt, H., Goldsberry, A., Houser, M. T., Krauth, M., Heerspink, H. J. L., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1306033 · Cited by 1,051
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
Kelley, D. E., & Mandarino, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.5.677 · Cited by 1,017
Bardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes
Pergola, P. E., Raskin, P., Toto, R. D., Meyer, C. J., Huff, J. W., Grossman, E. B., Krauth, M., Ruiz, S., Audhya, P., Christ-Schmidt, H., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105351 · Cited by 890
Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment
Tonneijck, L., Muskiet, M. H. A., Smits, M. M., van Bommel, E. J., Heerspink, H. J. L., van Raalte, D. H., & Joles, J. A. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016060666 · Cited by 887
Inzucchi, S. E., Zinman, B., Fitchett, D., Wanner, C., Ferrannini, E., Schumacher, M., Schmoor, C., Ohneberg, K., Johansen, O. E., George, J. T., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1096 · Cited by 740
Vallon, V., & Thomson, S. C. (2017) · Diabetologia · doi:10.1007/s00125-016-4157-3 · Cited by 635
Self-citation
Cited by
Sorted by citations
Diabetic vascular diseases: molecular mechanisms and therapeutic strategies
Li, Y., Liu, Y., Liu, S., Gao, M., Wang, W., Chen, K., Huang, L., & Liu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01400-z · Cited by 799
Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2
Stenvinkel, P., Chertow, G. M., Devarajan, P., Levin, A., Andreoli, S. P., Bangalore, S., & Warady, B. A. (2021) · Kidney International Reports · doi:10.1016/j.ekir.2021.04.023 · Cited by 327
Diabetes mellitus—Progress and opportunities in the evolving epidemic
Abel, E. D., Gloyn, A. L., Evans‐Molina, C., Joseph, J. J., Misra, S., Pajvani, U. B., Simcox, J., Suszták, K., & Drucker, D. J. (2024) · Cell · doi:10.1016/j.cell.2024.06.029 · Cited by 350
An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors
Salvatore, T., Galiero, R., Caturano, A., Rinaldi, L., Martino, A. D., Albanese, G., Salvo, J. D., Epifani, R., Marfella, R., Docimo, G., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073651 · Cited by 279
Inflammation and Oxidative Stress in Chronic Kidney Disease and Dialysis Patients
Ebert, T., Neytchev, O., Witasp, A., Kublickiene, K. R., Stenvinkel, P., & Shiels, P. G. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8184 · Cited by 197
Metadata
- Authors
- Hesp, A. C., Schaub, J. A., Prasad, P. V., Vallon, V., Laverman, G. D., Bjornstad, P., & van Raalte, D. H.
- Affiliations
- Amsterdam University Medical Centers (NL)
- University of Michigan (US)
- Endeavor Health (US)
- University of California San Diego (US)
- Ziekenhuis Groep Twente (NL)
- University of Colorado Anschutz (US)
- Corresponding author
- Hesp, Anne C.
- ORCID
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 98
- Issue
- 3
- Pages
- 579-589
- ISSN
- 0085-2538 (ISSN-L)
- PMC
- PMC8397597
- OpenAlex
- W3020088156
- Cited by
- 202
- References
- 120
- Citations by year
- 2026: 30 · 2025: 34 · 2024: 25 · 2023: 38 · 2022: 40 · 2021: 32 · 2020: 3
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK106557)
- National Institutes of Health (R01DK112042, R01DK106102, R01HL142814, RF1AG061296)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- diabetic nephropathy, renal hypoxia, oxygen delivery, oxygen requirement, sodium-glucose cotransporter 2 inhibition, SGLT2 inhibitors, renal perfusion, glomerular hyperfiltration, sodium reabsorption, renal fibrosis, extracellular matrix deposition, BOLD MRI, renal protection, end-stage renal disease
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Hypoxia, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Humans, Hyperglycemia, Hypoglycemic Agents, Kidney
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
