Discussion
CKD, diabetes, autosomal dominant polycystic kidney disease, kidney failure, albuminuria
DIABETES, AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE, KIDNEY FAILURE, TYPE 1 DIABETES MELLITUS
Our analyses show that in this cohort of patients with CKD at risk of
progression, allocation to empagliflozin causes a small dip in kidney function of
approximately 2 mL/min/1.73mThe acute dip in eGFR when empagliflozin was initiated in EMPA-KIDNEY was
modest (in all participant subgroups it was on average less than 3
mL/min/1.73mOur analyses focussed on chronic slopes. Although effects on total slope
correlate strongly with effects on clinical outcomes over short (2-3 year) follow-up
periods,When comparing chronic slopes, we have reported both the absolute and
relative differences but have emphasised the latter. Absolute differences are
determined by both the background annual rate of change in eGFR and the relative
effect of treatment, so any heterogeneity observed could be due to either of these
components. This is demonstrated in the analysis by baseline uACR: the absolute
difference in chronic slope among participants with uACR ≥2000 mg/g was 1.84
mL/min/1.73mThese analyses are limited by the characteristics of patients included in
EMPA-KIDNEY. Few patients with type 1 diabetes mellitus were included, and patients
with autosomal dominant polycystic kidney disease or with a kidney transplant were
not eligible for the trial. The trial deliberately excluded patients at low risk of
CKD progression (i.e., those with eGFR ≥45 mL/min/1.73mIn summary, in EMPA-KIDNEY allocation to empagliflozin caused a modest acute
dip in eGFR, and then substantially slowed the longer-term progression of CKD. The
longer-term benefits varied by diabetes status, eGFR and most prominently uACR (and
related characteristics such as predicted risk of kidney failure). Although the
trial stopped early because of clear benefits emerging based on results in the
highest risk patients, these analyses show that patients at lower risk such as those
with lower levels of albuminuria - many of whom in their lifetime would otherwise
develop kidney failure - could benefit in terms of preservation of kidney function,
in addition to other proven cardiovascular and mortality benefits.