Dapagliflozin therapy not linked to renal damage in heart failure patients

A new study by Nakase and team showed that patients with heart failure with a reduced ejection fraction (HFrEF) who saw a brief drop in estimated glomerular filtration rate (eGFR) after starting dapagliflozin did not often have renal tubular damage, and the drop might have been caused by a hemodynamic change instead. The findings of this study were published in Internal Medicine.

Uncertainty exists regarding the connection between the early decline in glomerular filtration rate (GFR) following the start of sodium-glucose co-transporter 2 inhibitors (SGLT2) and renal tubular damage in patients with heart failure and a low ejection fraction. Therefore, this study looked at how dapagliflozin treatment in individuals with HFrEF affected changes in estimated GFR and urine N-acetyl-D-glucosaminidase (uNAG).

Researchers looked at 89 individuals with HFrEF who had recently begun using dapagliflozin 10 mg/day for this trial. After starting dapagliflozin, changes in the eGFR and uNAG-to-creatinine ratio (uNAG/Cre) were assessed after 2 weeks and 2 months.

The key findings of this study were:

1. At two weeks, the eGFR started to fall, but by two months, it hadn't dropped any lower.

2. The uNAG/Cre was raised at two weeks, but by two months, it had not gone up any more.

3. The eGFR alterations and the uNAG/Cre changes did not correlate.

4. The relative change in the eGFR was linked with the relative change in the systolic blood pressure, hematocrit, plasma volume, and N-terminal pro-brain natriuretic peptide (NT-proBNP).

5. In a multiple linear regression analysis, the proportional change in urine osmolality at two weeks and the usage of loop diuretics were both substantially correlated with the relative change in uNAG/Cre and the relative change in eGFR at two weeks, respectively.

A brief drop in the eGFR in individuals with HFrEF following the start of dapagliflozin was not linked to renal tubular damage as determined by the NAG/Cre and may have been caused by a hemodynamic change. Although the concurrent use of loop diuretics and higher urine osmolality might cause tubular damage in HFrEF patients, additional WRF is unlikely to develop.

Reference: 

Nakase, M., Ninomiya, K., Horiuchi, Y., Sekiguchi, M., Watanabe, Y., Setoguchi, N., Asami, M., Yahagi, K., Yuzawa, H., Komiyama, K., Tanaka, J., Aoki, J., & Tanabe, K. (2023). Impact of dapagliflozin on the renal function and damage in patients with heart failure with a reduced ejection fraction. Internal Medicine (Tokyo, Japan). https://doi.org/10.2169/internalmedicine.1506-22