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. 2024 Jan;41(1):292-314.
doi: 10.1007/s12325-023-02683-y. Epub 2023 Nov 8.

Predictors of Kidney Function Outcomes and Their Relation to SGLT2 Inhibitor Dapagliflozin in Patients with Type 2 Diabetes Mellitus Who Had Chronic Heart Failure

Tetiana A Berezina  1 , Ivan M Fushtey  2 , Alexander A Berezin  2   3 , Sergii V Pavlov  4 , Alexander E Berezin  5   6
Affiliations

Predictors of Kidney Function Outcomes and Their Relation to SGLT2 Inhibitor Dapagliflozin in Patients with Type 2 Diabetes Mellitus Who Had Chronic Heart Failure

Tetiana A Berezina et al. Adv Ther. 2024 Jan.

Abstract

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have a favorable impact on the kidney function in patients with heart failure (HF), while there is no clear evidence of what factors predict this effect. The aim of the study was to identify plausible predictors for kidney function outcome among patients with HF and investigate their association with SGLT2i.

Methods: We prospectively enrolled 480 patients with type 2 diabetes mellitus (T2DM) treated with diet and metformin and concomitant chronic HF and followed them for 52 weeks. In the study, we determined kidney outcome as a composite of ≥ 40% reduced estimated glomerular filtration rate from baseline, newly diagnosed end-stage kidney disease or kidney replacement therapy. The relevant medical information and measurement of the biomarkers (N-terminal natriuretic pro-peptide, irisin, apelin, adropin, C-reactive protein, tumor necrosis factor-alpha) were collected at baseline and at the end of the study.

Results: The composite kidney outcome was detected in 88 (18.3%) patients of the entire population. All patients received guideline-recommended optimal therapy, which was adjusted to phenotype/severity of HF, cardiovascular risk and comorbidity profiles, and fasting glycemia. Levels of irisin, adropin and apelin significantly increased in patients without clinical endpoint, whereas in those with composite endpoint the biomarker levels exhibited a decrease with borderline statistical significance (p = 0.05). We noticed that irisin ≤ 4.50 ng/ml at baseline and a ≤ 15% increase in irisin serum levels added more valuable predictive information than the reference variable. However, the combination of irisin ≤ 4.50 ng/ml at baseline and ≤ 15% increase in irisin serum levels (area under curve = 0.91; 95% confidence interval = 0.87-0.95) improved the discriminative value of each biomarker alone.

Conclusion: We suggest that low levels of irisin and its inadequate increase during administration of SGLT2i are promising predictors for unfavorable kidney outcome among patients with T2DM and concomitant HF.

Keywords: Adropin; Apelin; Circulating biomarkers; Dapagliflozin; Heart failure; Irisin; Kidney outcome; Natriuretic peptides.

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Conflict of interest statement

The authors of the paper (Tetiana A. Berezina, Ivan M. Fushtey, Alexander A. Berezin, Sergii V. Pavlov and Alexander E. Berezin) declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Study design. ESKD end-stage chronic kidney disease, eGFR estimated glomerular filtration rate, HF heart failure, hs-CRP high sensitivity C-reactive protein, NT-proBNP N-terminal brain natriuretic pro-peptide, TNF-alpha tumor necrosis factor alpha
Fig. 2
Fig. 2
Dynamic changes in the biomarker levels in peripheral blood in patients during dapagliflozin administration. Δ% respective change in biomarker levels
Fig. 3
Fig. 3
Levels of NT-proBNP, irisin, adropin, apelin and TNF-alpha in prediction of composite endpoint: receiver-operating characteristic curve analysis. AUC area under curve, CI confidence interval, ROC receiver-operating characteristic curve
See this image and copyright information in PMC

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