Acute reduction in eGFR on dapagliflozin does not correlate with greater CKD progression
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Among patients with chronic kidney disease and albuminuria treated with dapagliflozin, researchers did not identify a correlation between acute reduction in eGFR and higher rates of CKD progression.
Although dapagliflozin can reduce the risk of kidney failure in those with CKD, according to researchers, the treatment can also lead to reversible acute reduction in eGFR at the start of treatment.
In a post hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD), Hiddo J. L. Heerspink, PhD, professor of clinical trials and personalized medicine and a clinical pharmacologist/trialist in the department of clinical pharmacy and pharmacology at the University Medical Center Groningen in the Netherlands, and colleagues examined 4,304 adults with CKD and albuminuria to measure relationships and consequences of an acute reduction in eGFR after starting dapagliflozin treatment.
Researchers randomized patients to either dapagliflozin 10 mg or placebo once daily, then conducted follow-up visits after 2 weeks; at 2, 4 and 8 months; and at 4-month intervals. Patients were masked to treatment allocation, which was added to standard care.
eGFR was calculated using the CKD Epidemiology Collaboration, and researchers categorized patients by percentage decline in eGFR at week 2 as greater than 10% decline (defined as acute eGFR drop); between 0% and 10% decline (acute modest eGFR drop); and no decline (acute eGFR increase).
Researchers considered the primary outcome a composite of sustained 50% or greater decline in eGFR, onset of end-stage kidney disease, kidney transplantation or an eGFR of less than 15 mL/min per 1.73 m2 by the second measurement or death.
Using logistic regression, researchers determined the changes of experiencing an acute reduction in eGFR greater than 10 % at week 2 with dapagliflozin compared with placebo.
Overall, 4,157 of patients had eGFR data available at baseline and at 2 weeks and were therefore included in the final analysis. Researchers observed an acute reduction in eGFR of greater than 10% in 49.4% of the dapagliflozin group and 23.7% of the placebo group. These patients in the dapagliflozin group experienced a long-term eGFR decline of –1.58 mL/min per 1.73 m2 per year compared with –2.44 mL/min per 1.73 m2 and –2.48 mL/min per 1.73 m2 per year among those experiencing a less pronounced reduction or increase in eGFR, respectively.
Similarly, the long-term eGFR decline among the placebo group was –3.27 mL/min per 1.73 m2, –3.84 mL/min per 1.73 m2 and –3.77 mL/min per 1.73 m2 per year for acute eGFR reduction subgroups of greater than 10%, greater than 0% to 10% or increase in eGFR.
Researchers noted that adverse events in patients randomized to dapagliflozin were not linked to the acute eGFR change.
“In this study of patients with CKD and albuminuria enrolled in the DAPA-CKD trial, we demonstrated that an acute reduction in eGFR is more common in patients receiving dapagliflozin compared with placebo,” Heerspink and colleagues wrote. “Among dapagliflozin-treated patients, a larger acute reduction in eGFR was associated with an attenuated chronic eGFR slope and was not associated with increased risk of the primary composite end point or the secondary composite kidney end point.”
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