Empagliflozin in ADPKD: well tolerated in a 50-patient pilot, but kidneys grew faster on the drug
In a 50-patient randomized, placebo-controlled pilot in polycystic kidney disease, empagliflozin was well tolerated, but total kidney volume grew about 10% a year on the drug, against about 5% on placebo. A secondary outcome in a small trial, but the investigators say it should give us pause.
🎧 Listen: Weekly · Oct 26, from 10:20.
The question
SGLT2 inhibitors slow CKD across many causes, but people with autosomal dominant polycystic kidney disease were left out of the large trials, so the class has been held back in ADPKD. There was a specific worry: these drugs increase urinary salt and water loss, which can raise vasopressin, the hormone that drives cyst growth.
What the trial did
This blinded pilot and feasibility trial (Colorado and Maryland) randomized 50 adults aged 18 to 55 with ADPKD at high risk of progression (Mayo class 1C to 1E), an eGFR of 30 to 90 and no diabetes, to empagliflozin 25 mg daily (after 10 mg for the first month) or placebo for 12 months. People taking tolvaptan or loop diuretics were excluded. The primary outcome was safety and tolerability; height-adjusted total kidney volume was one of several secondary outcomes. The trial was presented at Kidney Week (SA-OR074).
What they found
- Tolerability: 24 of 25 (96%) in each group tolerated the full dose. Urinary tract infections 2 vs 0 (treated with oral antibiotics; not cyst infections), genital infection 1 vs 0, acute kidney injury 0 vs 1.
- Kidney volume: grew 10.5% a year on empagliflozin (95% CI, 8.2 to 12.7) vs 5.1% on placebo (3.0 to 7.3), a difference of 5.0% a year (2.0 to 8.1).
- eGFR: the expected dip in the first month (about −6 vs 0), then a chronic slope of −0.77 vs −2.87 per year. That difference was not statistically significant; a gap that size could be chance, and the pilot wasn't designed to answer it.
- No differences in pulse wave velocity, copeptin (a marker of vasopressin), urine KIM-1 or the ADPKD Impact Scale.
Why it matters
The investigators, speaking on ASN's Kidney Translation podcast, called the size of the effect surprising and said it should give us some pause. FDA labeling and current consensus guidance do not recommend SGLT2 inhibitors to slow ADPKD. Our take: in polycystic kidney disease alone, hold the SGLT2 inhibitor until larger trials report.
Caveats
The authors caution that five secondary outcomes were tested without adjustment for multiple comparisons, so a chance finding can't be excluded. More patients on the drug were Mayo class 1E (32% vs 20%), although adjusting for it did not change the result. The 25 mg dose is higher than the 10 mg used in the CKD trials, and an ongoing efficacy trial uses lower doses. Fifty people is too few to rule a vasopressin effect in or out.
Funding and ties: funded by the NIDDK and the PKD Foundation, with other foundation and university support; no industry funding is reported. Authors' disclosure forms are available with the article.
The source: Seliger SL, Gitomer B, You Z, et al. Empagliflozin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Randomized Controlled Trial. J Am Soc Nephrol. Published online October 24, 2026. doi:10.1681/ASN.0000001271 Read the original
🎧 Listen: Weekly · Oct 26, from 10:20.
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