A modest acute dip in estimated glomerular filtration rate (eGFR) within 2 weeks of dapagliflozin initiation does not increase progression risk in patients with chronic kidney disease (CKD), investigators report.
In the DAPA-CKD trial, more patients receiving dapagliflozin than placebo (49.4% vs 23.7%) experienced an acute reduction in eGFR exceeding 10%. At study entry, all patients had an eGFR of 25-75 mL/min/1.73 m2 and a urine albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, with or without type 2 diabetes.
The rate of annual eGFR decline (in mL/min/1.73 m2) was -1.58 for dapagliflozin recipients who had an initial eGFR dip of more than 10% compared with -2.44 and -2.48 among patients with a less pronounced eGFR dip or an initial eGFR increase, respectively, Hiddo J.L. Heerspink, PhD, PharmD, of the University Medical Centre Groningen in The Netherlands, and colleagues reported in the Journal of the American Society of Nephrology. The placebo group experienced greater annual eGFR decline: -3.27, -3.84, and -3.77 among patients with an initial eGFR dip of more than 10% and less than 10% or an initial eGFR increase, respectively.
“These data suggest that the acute reduction in eGFR could reflect a dapagliflozin-induced reduction in glomerular hyperfiltration,” according to Dr Heerspink’s team.
Patients who were older with high blood pressure, high body mass index, or low hemoglobin, or used diuretics were more likely to experience a larger initial eGFR dip. More patients with a large acute eGFR dip experienced hypoglycemia, kidney events, and volume depletion, whether in the dapagliflozin or placebo group.
“These reassuring efficacy and safety data suggest that it seems reasonable that for the majority of patients there is no need to routinely check electrolytes or kidney function shortly after initiating dapagliflozin unless there is clinical concern for volume depletion such as in elderly patients who are treated with high doses of diuretics,” the investigators stated.
Sodium glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, have been shown to slow kidney function decline and reduce kidney failure risk in patients with type 2 diabetes, heart failure, and CKD. However, the acute eGFR dip after drug initiation may have prompted some clinicians to forgo or discontinue these agents due to safety concerns.
The reversible acute decline in eGFR following initiation of dapagliflozin therapy should not be a reason to discontinue the drug, Dr Heerspink’s team concluded.
This study was a post hoc analysis, so confounding cannot be ruled out. It was not powered to assess the effects of large acute reductions in eGFR (eg, 30% or more).
Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.
Jongs N, Chertow G, Greene T, et al. Correlates and consequences of an acute change in eGFR in response to the SGLT2 inhibitor dapagliflozin in patients with chronic kidney disease. J Am Soc Nephrol. August 2022. doi:10.1681/ASN.2022030306