Abstract: FR-OR090

Effect of the SGLT-2 Inhibitor Dapagliflozin on Glomerular and Tubular Injury Markers

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Dekkers, Claire, University Medical Center Groningen, Groningen, Netherlands
  • Petrykiv, Sergei, None, Groningen, GRONINGEN, Netherlands
  • Laverman, Gozewijn Dirk, ZGT Almelo, Almelo, Overijssel, Netherlands
  • Gansevoort, Ron T., UMC Groningen, Groningen, Netherlands
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
Background

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to delay progression of kidney function decline in type 2 diabetes. However, an FDA communication reported potential risk of acute kidney injury (AKI) particular during the first weeks of treatment, potentially due to tubular injury. Here we assessed effects of the SGLT2 inhibitor dapagliflozin (DAPA) on markers of subclinical tubular injury.

Methods

Data was used from a randomized controlled cross-over trial in 33 patients with type 2 diabetes and albuminuria ≥100 mg/g designed to assess the albuminuria lowering effect of 6-weeks treatment with DAPA 10 mg/d. IgG and IgG4 were measured as markers of glomerular damage and fractional excretion of the IgG to IgG4 ratio was used as proxy of charge selectivity. Urinary KIM-1, NGAL and LFABP were assessed as tubular damage markers, whereas urinary MCP-1 and urinary IL-6 were measured as inflammation markers.

Results

Compared to placebo, DAPA decreased IgG and IgG4 excretion, but did not change the glomerular charge selectivity index (table 1). Compared to placebo, DAPA decreased urinary KIM-1 excretion, whereas no change in NGAL and LFABP was observed. The inflammatory marker IL-6 significantly decreased during DAPA therapy. DAPA also decreased albuminuria (36.2% [95%CI 22.9, 47.2]) and eGFR (5.3 ml/min/1.73m2 [8.0, 2.7]). Albuminuria change tended to correlate with eGFR change during DAPA (r=0.34; p=0.06). Tubular injury markers did not correlate with change in eGFR. Changes in IgG, MCP-1 and IL-6 significantly correlated with change in albuminuria (all p<0.02).

Conclusion

DAPA lowers urinary excretion of glomerular and tubular injury markers as well as inflammation markers. These data indicate that the fall in eGFR after start of dapagliflozin reflects a hemodynamic response and not (subclinical) tubular injury.

Table 1
Injury markersMean change % from baseline compared to placebo (95% CI)P-value
IgG-28.4 (-7.2, -44.7)0.01
IgG4-34.6 (-3.0, -55.9)0.04
IgG/IgG417.8 (-25.2, 85.4)0.46
KIM-1-22.6 (-0.3, -39.8)0.05
NGAL-13.4 (-35.6, 16.6)0.33
LFABP0.9 (-13.2, 17.2)0.91
IL-6-23.5 (-1.4, -40.6)0.04
MCP-1-14.1 (-32.2, 8.8)0.20