eGFR dip does not influence outcomes in T2D patients on empagliflozin

An eGFR* decline of >10 percent did not appear to influence kidney outcomes in individuals receiving empagliflozin for type 2 diabetes, according to data presented at ERA-EDTA 2020.

“[A]n initial eGFR dip … was consistently reported across the class of SGLT2** inhibitors … Although this is considered haemodynamic and largely reversible, this has raised concerns in clinical practice,” said Dr Bettina Kraus from the University Hospital Würzburg in Germany who presented the findings.

A post hoc analysis was conducted to weigh the implications of an initial eGFR dip and determine predictive baseline factors. Using data from EMPA-REG OUTCOME*** comparing empagliflozin 10 and 25 mg (n=4,443 [pooled]) against placebo (n=2,225), participants were classified according to eGFR declines from baseline to week 4: dippers (>10 percent), intermediate (≤10 percent), and nondippers (none, or with increased eGFR). [ERA-EDTA 2020, abstract LBCT 4547]

“We recognized that empagliflozin caused a shift towards more patients [being] categorized as eGFR dippers,” said Kraus. With placebo, 13 percent had experienced a >10-percent dip; this has more than doubled (28 percent) with empagliflozin.

Nonetheless, week 12 saw a “nice rebound”, said Kraus, followed by a consistent stabilization across all categories until 192 weeks. “Dippers returned to about 50 percent of the initial dip and regained some of the eGFR after 12 weeks … [T]hat was very reassuring.”

The rates of participants with a more pronounced eGFR decline (>30 percent) – which is regarded as alarming – were low (1.4 percent and 0.9 percent for empagliflozin and placebo, respectively). Kraus underscored however that this needs further exploration to determine other potential underlying causes for AKI^#, volume depletion, etc.

Diuretic use and KDIGO^## risk category were identified as predictive of an eGFR dip of >10 percent (odds ratios [ORs], 3.6, 4.7, and 4.4 for moderate, high, and very high risk groups, respectively). “[These suggest] that patients on diuretics and with at least moderately increased KDIGO risk are the ones most likely experiencing such a dip,” said Kraus.

The incidence of serious adverse events among empagliflozin recipients on diuretic therapy in the high and very high KDIGO risk category were 28.7 percent and 41.6 percent, respectively. Nonetheless, these were lower than placebo (36.5 and 45.5, respectively).

A reduction in incident or worsening nephropathy (hazard ratio [HR], 0.61) and hard kidney outcomes (HR, 0.54) was observed with empagliflozin vs placebo. A similar effect was seen in patients with increased dipping OR of >2.7 (HR, 0.56 and 0.70, respectively). The risk for nephropathy at week 4 was sustained irrespective of adjustments for eGFR dip (HR, 0.58), suggesting that such a dip did not influence the risk.

“[Taken together,] these data show that around one in four empagliflozin-treated patients experiences an initial eGFR dip. This was more likely in those taking diuretics and/or in more advanced stages of CKD^###. [Nonetheless,] empagliflozin was safe and effective,” commented ERA-EDTA President-elect Professor Christoph Wanner from Würzburg, Germany. “For such high-risk patients … any intervention that slows the progression of kidney disease and allows the need for dialysis to be postponed as long as possible [is welcome].”