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Cited by 165Chronic Kidney Disease and DiabetesPeroxisome Proliferator-Activated ReceptorsAcute Kidney Injury Research

The Evolving Understanding of the Contribution of Lipid Metabolism to Diabetic Kidney Disease

Open access
Stadler, Krisztian, Goldberg, Ira J., Susztak, Katalin·2015·Current Diabetes Reports
DOI 10.1007/s11892-015-0611-8PMC PMC4548922
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Abstract

Although diabetes is mainly diagnosed based on elevated glucose levels, dyslipidemia is also observed in these patients. Chronic kidney disease (CKD), a frequent occurrence in patients with diabetes, is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. At baseline, most renal epithelial cells rely on fatty acids as their energy source. CKD, including that which occurs in diabetes, is characterized by tubule epithelial lipid accumulation. Whether this is due to increased uptake or greater local fatty acid synthesis is unknown. We have recently shown that CKD also leads to decreased fatty acid oxidation, which might be an additional mechanism leading to lipid accumulation. Defective fatty acid utilization causes energy depletion resulting in increased apoptosis and dedifferentiation, which in turn contributes to fibrosis and CKD progression. Enhanced fatty acid oxidation in the kidney induced by fenofibrate, a peroxisomal proliferator-activated receptor (PPAR)-α agonist, showed benefit in mouse models of CKD. Fenofibrate treatment also reduced albuminuria in patients with diabetes in multiple clinical trials. Taken together, these findings suggest that further understanding of lipid metabolism in diabetic kidney disease may lead to novel therapeutic approaches.

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  • Lipid accumulation in glomeruli and tubules may lead to fibrosis and accelerated CKD progression.

    “Dyslipidemia and abnormalities in renal lipid metabolism may predispose diabetic individuals to lipid accumulation in glomeruli and tubules, which may lead to fibrosis and accelerated CKD progression.9, 10”

    From Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes (2019) · cites this paper as [10]

    The Introduction (page not provided) links lipid deposition in glomeruli and tubules with kidney injury, and the Abstract links defective fatty-acid utilization to fibrosis and CKD progression. But the ‘Lipid Accumulation—Lipotoxicity Versus Lipid Overload’ section reports that lipid accumulation alone did not cause fibrosis in a mouse model. The claim omits that distinction between lipid accumulation and harmful defects in lipid metabolism. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Fenofibrate may have renoprotective effects by affecting circulating lipid levels.

    “Fenofibrate may have renoprotective effects by affecting circulating lipid levels.”

    From Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes (2019) · cites this paper as [10]

    The Clinical Implications section reports reduced albuminuria with fenofibrate and a small benefit for GFR decline, supporting possible renoprotection. It does not establish that this benefit comes from changing circulating lipids: the reported GFR effect was independent of serum triglyceride levels and may reflect an intrarenal mechanism. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Dyslipidemia and abnormalities in renal lipid metabolism may predispose diabetic individuals to lipid accumulation in glomeruli and tubules.

    “Dyslipidemia and abnormalities in renal lipid metabolism may predispose diabetic individuals to lipid accumulation in glomeruli and tubules, which may lead to fibrosis and accelerated CKD progression.9, 10”

    From Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes (2019) · cites this paper as [10]

  • Experimental studies demonstrate that fenofibrate increases fatty acid oxidation and protects against renal fibrosis in animals.

    “Experimental studies support this hypothesis by demonstrating that fenofibrate increases fatty acid oxidation and protects against renal fibrosis in animals.10”

    From Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes (2019) · cites this paper as [10]

  • Previous studies have suggested that high lipid levels and altered lipid metabolism in diabetic kidney disease may contribute to kidney function decline.

    “Previous studies have suggested that high lipid levels and altered lipid metabolism in diabetic kidney disease may contribute to kidney function decline.9, 10”

    From Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes (2019) · cites this paper as [10]

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Cited by

Sorted by citations

Authors
Stadler, K., Goldberg, I. J., & Susztak, K.
Affiliations
New York University (US)
ORCID
Goldberg, Ira J.
Venue
Current Diabetes Reports
Publisher
Springer Science and Business Media LLC
Published
2015-05-10
Volume
15
Issue
7
Pages
40-40
ISSN
  • 1534-4827 (ISSN-L)
  • 1539-0829
DOI
10.1007/s11892-015-0611-8
PMC
PMC4548922
OpenAlex
W812844120
Cited by
165
References
10
Citations by year
2026: 4 · 2025: 9 · 2024: 13 · 2023: 27 · 2022: 21 · 2021: 19 · 2020: 18 · 2019: 16 · 2018: 10 · 2017: 19 · 2016: 6 · 2015: 3
FWCI
1.94
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Current Diabetes Reports (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL045095, HL073029, R01HL073029, HL45095, R37HL045095)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087635, DK087635, DK-095684, DK076077, R01DK095684, R01DK076077)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
diabetic nephropathy, renal lipid metabolism, fatty acid oxidation, chronic kidney disease, fenofibrate, PPARα agonist, albuminuria, renal fibrosis, dedifferentiation, apoptosis, dyslipidemia, lipoproteins
MeSH terms
Animals, Diabetic Nephropathies, Energy Metabolism, Epithelial Cells, Fatty Acids, Humans, Peroxisome Proliferator-Activated Receptors, Lipid Metabolism

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