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Albuminuria and Serum Tumor Necrosis Factor Receptor Levels in Patients with Type 2 Diabetes on SGLT2 Inhibitors: A

Toshiki Otoda1, Akiko Sekine2, Ryoko Uemoto2

  • 1Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 18-15, 3 Chome, Kuramoto-cho, Tokushima, 770-8503, Japan. otoda.toshiki@tokushima-u.ac.jp.

Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders
|October 26, 2023
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce proteinuria in diabetic kidney disease. This study found decreased albuminuria after SGLT2i treatment was linked to reduced serum tumor necrosis factor receptor levels in type 2 diabetes patients.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) show proteinuria-reducing effects in diabetic kidney disease, even with renin-angiotensin inhibitor use.
  • The exact mechanism behind SGLT2i's renal benefits remains unclear.
  • This study explored factors linked to proteinuria reduction following SGLT2i administration.

Purpose of the Study:

  • To investigate the association between changes in proteinuria and biomarkers of kidney injury, inflammation, and oxidative stress after SGLT2i treatment.
  • To identify clinical indicators, such as serum tumor necrosis factor receptors (TNFR), associated with reduced albuminuria in type 2 diabetes patients.

Main Methods:

  • A prospective, open-label, single-arm study involving 123 patients with type 2 diabetes (T2DM).
  • Participants received SGLT2 inhibitors for 4 months, with primary outcomes being changes in urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABPCR).
  • Secondary endpoints included changes in kidney injury markers, and correlation analyses were performed for clinical indicators like serum TNFR1 and TNFR2.

Main Results:

  • SGLT2i treatment led to a significant reduction in uACR (from 19.2 to 13.3 mg/gCr).
  • No significant change was observed in uL-FABPCR.
  • Changes in serum TNFR1 levels positively correlated with reduced uACR, and this association remained independent in multivariate analysis.

Conclusions:

  • SGLT2i administration for 4 months decreased albuminuria in T2DM patients.
  • The reduction in albuminuria was associated with a decrease in serum TNFR levels.
  • Serum TNFR levels may play a role in the renoprotective effects of SGLT2i.
Keywords:
AlbuminuriaDiabetic kidney diseaseInflammationSodium-glucose cotransporter 2 inhibitorsTumor necrosis factor receptorType 2 diabetes

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