Kidney Week

Abstract: FR-PO0492

Effects of SGLT2 Inhibitors on YKL-40 Levels in Diabetic Kidney Disease

Session Information

• CKM: Clinical - Trials, Epidemiology, and Biomarkers
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Helvaci, Ozant, Gazi Universitesi, Ankara, Turkey

Ozant Helvaci, MD

• Karaoglan, Aysegul, Gazi Universitesi, Ankara, Turkey

Aysegul Karaoglan, MD

• Helvaci, Burcak Cavnar, TC Saglik Bakanligi Ankara Etlik Sehir Hastanesi, Ankara, Turkey

Burcak Cavnar Helvaci

• Demirezen, Asil, Gazi Universitesi, Ankara, Turkey

Asil Demirezen, MD

• Guz, Galip, Gazi Universitesi, Ankara, Turkey

Galip Guz, MD

• Pasaoglu, Hatice, Gazi Universitesi, Ankara, Turkey

Hatice Pasaoglu, DrMed

Background

SGLT-2 inhibitors demonstrate renal and cardiovascular benefits that occur rapidly and independently of glycemic control, suggesting additional mechanisms beyond glucose lowering. Chronic low-grade inflammation is central to the progression of diabetic kidney disease, yet routinely measured parameters fail to capture this process. YKL-40 (chitinase-3-like protein 1), a glycoprotein secreted by macrophages, neutrophils, and vascular smooth muscle cells, has emerged as a biomarker of inflammation, fibrosis, and endothelial dysfunction. Elevated YKL-40 levels are reported in type 2 diabetes and across stages of diabetic nephropathy, and have been associated with albuminuria, eGFR decline, and adverse cardiovascular outcomes. Whether SGLT-2 inhibitors modulate YKL-40 remains unknown. We investigated whether SGLT-2 inhibitors modify this inflammatory pathway in diabetic kidney disease.

Methods

This prospective study included 100 patients with diabetic kidney disease (stages 2–4). Patients were enrolled before initiation of SGLT-2 inhibitors and received either dapagliflozin (n=50) or empagliflozin (n=50). Demographic, clinical, and laboratory data were recorded. Serum YKL-40 was measured by ELISA at baseline and after mean 48±12 days (33–81 days) of treatment.

Results

Mean age was 65±10 years, 53% were male, and baseline eGFR was 52±18 mL/min/1.73m². SGLT-2 inhibitor treatment significantly reduced serum YKL-40 levels by 27% (69.9±35.3 vs 51.3±35.8 ng/mL, p<0.001). The reduction was accompanied by significant decreases in albumin/creatinine ratio (586 vs 387 mg/g, p<0.001) and protein/creatinine ratio (1236 vs 810 mg/g, p=0.012). No relevant differences were observed between dapagliflozin and empagliflozin groups at baseline or follow-up (p>0.05 for all comparisons).

Conclusion

SGLT-2 inhibitors significantly reduced YKL-40 levels within weeks of treatment initiation in patients with diabetic kidney disease, in parallel with improvements in albuminuria. These findings identify attenuation of systemic inflammation as a potential mechanism underlying SGLT-2 inhibitor renal benefits, and may help explain why these agents act rapidly beyond glucose lowering. To our knowledge, this is the first study to demonstrate SGLT-2 inhibitor effects on YKL-40 specifically in patients with diabetic kidney disease.

Acknowledgment

This study was supported by Gazi University Scientific Research Projects Unit (Project No: TTU-2024-9496).