• In general, blood pressure-lowering therapies still preserve kidney function even when eGFR dips occur at initiation.
• eGFR dips exceeding 30% are cause for concern.

PHILADELPHIA — Medications that reduce blood pressure and improve glycemia may preserve kidney function over time despite initial eGFR dips, according to a speaker at the Heart in Diabetes CME Conference.

Matthew R. Weir, MD, professor and chief in the division of nephrology at University of Maryland School of Medicine, said eGFR dips “should be expected and planned upon” when using BP-lowering medications and should not deter clinicians from using them.

“An eGFR dip is cause of concern when it is more than 30%,” Weir told Healio. “But you have to carefully individualize. If an eGFR dip starts and it keeps getting worse, that’s a bad sign.”

Various trials on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have explored associations between eGFR dips and kidney function. In a meta-analysis published in JAMA Internal Medicine in 2000, Weir and George L. Bakris, MD, found that an initial eGFR dip within the first 6 months of beginning treatment was predictive of better preservation of kidney function among patients treated with an ACE inhibitor or ARB.

In addition, a post hoc analysis of the ONTARGET/TRANSCEND trials in 2017 observed favorable outcomes when patients had an initial eGFR dip compared with patients with increased eGFR, Weir said. Results of the analysis showed that the risk for adverse kidney events decreased for those with an initial eGFR dip while the risk increased for patients who had an initial uptake in eGFR.

Studies on other therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, have also observed kidney benefits after initial eGFR dips, according to Weir. In the EMPA-REG Outcome trial, empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) demonstrated safety and efficacy for patients with type 2 diabetes and CVD, even when an initial eGFR dip was observed.

“The bottom line here is people on diuretics, people with lesser kidney function, are probably more likely to have a bit more of a dip when using an SGLT2 inhibitor,” Weir said in his presentation. “But overall, it did not appear to be a clinical concern.”

For GLP-1 receptor agonists, data from the FLOW trial showed that patients treated with semaglutide (Ozempic, Novo Nordisk) had a greater eGFR dip vs. placebo at 12 weeks but more preserved kidney function by week 208 compared with placebo, according to Weir.

Furthermore, data from the CONFIDENCE trial showed that among patients treated with finerenone (Kerendia, Bayer) and empagliflozin or either treatment alone, greater dips in eGFR were associated with better outcomes related to albuminuria, systolic BP and eGFR for both the combination therapy and both monotherapies, Weir said.

“The stabilization of eGFR decline in people with advanced [chronic kidney disease] should reassure clinicians that these therapies remain safe in hemodynamically stable patients with more advanced CKD stages,” Weir said.

Overall, an eGFR dip is generally associated with better kidney preservation outcomes, according to Weir. However, in cases where a patient’s eGFR dips more than 30%, careful monitoring is needed, he said.

“I would also like to point out that dipping of the estimated GFR is different between therapies and can be additive,” Weir said in his presentation. “You’re going to see a lot more [dips] with ACEs and ARBs than you are with the other three therapies that I discussed.”

Matthew R. Weir, MD, can be reached at nephrology@healio.com.