Daniel Fuster

Thank you Swiss National Science Foundation !! We just received 3.42 Mio CHF funding for our EMPASTONE trial. Looking forward to working with colleagues in Switzerland, Germany, France, Italy and the UK.
clinicaltrials.gov/study/NCT066...

YouTube video by MARKUS at HOMe SGLT-2 Inhibitoren & Nierensteine: SWEETSTONE - Prof. D. Fuster, Prof. S. Trelle (Bern, Schweiz)

Our new webinar in german language:

SGLT-2 Inhibitoren & Nierensteine: SWEETSTONE - Prof. D. Fuster, Prof. S. Trelle (Bern, Schweiz)

WATCH NOW:

youtu.be/i_YTcIQ4YQk?...

@danfuster.bsky.social
@gunnarheine.bsky.social
@marcussaemann.bsky.social

Thank you Pedro. Unfortunately not many groups working on these important transporters anymore.

PIP2-mediated oligomerization of the endosomal sodium/proton exchanger NHE9 Nature Communications - Na+ /H+ exchangers regulate intracellular pH, sodium levels, and cell volume. Cryo-EM structures reveal lipid coordination at the dimer interfaces of NhaA with cardiolipin...

Just out in Nature Communications…..a mystery solved. It’s all about lipids in the regulation of intracellular NHEs. Thank you David for this great collaboration.
rdcu.be/efxE2

visual abstract of NOSTONE and bone density from Hector

So @danfuster.bsky.social and colleagues seem to find HCTZ doesn’t work for anything!

In a post hoc analysis of NOSTONE (where CT scans were done in all & repurposed for calculating bone density) HCTZ doesn’t increase it vs placebo

journals.lww.com/cjasn/pages/... in @asnpublications.bsky.social

Hydrochlorothiazide and Bone Mineral Density in Patients with Kidney Stones: A Post Hoc Analysis of the NOSTONE Trial by Drs. Christe, @danfuster.bsky.social et al.

journals.lww.com/cjasn/abstra...

HCTZ up to 50 mg daily did not preserve BMD compared to placebo over 3 years!

Acid excretion is impaired in calcium oxalate stone formers Pedro H Imenez Silva, Nasser A Dhayat, Daniel G Fuster, Harald Seeger, Alexander Ritter, Thomas Ernandez, Florian Buchkremer, Beat Roth, Olivier Bonny, Isa

Happy to share that our research letter has been accepted in @ndt-era.bsky.social. Here we showed that impaired renal acid excretion is strongly associated with CaOx stone presence in the Swiss Kidney Stone Cohort: bit.ly/41rKodu. Many thanks to all co-authors in Switzerland for their support.

Hydrochlorothiazide and Bone Mineral Density in Patients... : Clinical Journal of the American Society of Nephrology three-year period. Methods: This post-hoc analysis was conducted on data from the NOSTONE trial, a multicenter, randomized, controlled study. A total of 416 adults with recurrent calcium stones par...

HCTZ not better than placebo for the prevention of BMD loss among individuals with calcium kidney stones

journals.lww.com/cjasn/abstra...

Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial - Nature Medicine As part of the SWEETSTONE trial, the authors report the ability of the sodium-glucose cotransporter 2 inhibitor empagliflozin to reduce the likelihood of kidney stone formation in individuals without ...

Excited to share the results of our SWEESTONE trial 🔥🔥🔥@NatureMedicine
Wonderful collaboration with colleagues @unibern @inselgruppe and DCR Bern.
www.nature.com/articles/s41...
Empagliflozin substantially reduced urinary supersaturations in non-diabetic patients with kidney stones.

Agree. This study shows nicely that it is dose equivalence and not type of thiazide that matters. CTD is ~2x more potent than HCT (and Indapamide ~20x more potent than HCT).

Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes This secondary analysis of a randomized clinical trial examines whether chlorthalidone is superior to hydrochlorothiazide in preventing kidney outcomes in patients with hypertension.

Chlorthalidone is not better than hydrochlorothiazide in kidney outcome prevention in a secondary analysis of the large DCP study. Very important results.
jamanetwork.com/journals/jam...

Not that I know of - and yes this should be done. Likely indirect effect in PT (as is the case for SGLT2i-mediated inhibition of NHE3), yet direct inhibition cannot be ruled out at this stage. NaDC1 has been a prime target for stone prevention for long-it seems SGLT2is are what we were looking for !

No - we were told first two weeks in January 25

Many putative mechanisms how RSR CaP can affect CaOx stone formation (Randall, heterogeneous nucleation etc), but also threats ( increase in urine calcium). This is why we need outcome data

Went up slightly from 30 to 35 mmol/d.

SGLT2is likely inhibit citrate reabsorption in the PT. No need for alkalosis. Urine citrate and pH drove reduction in RSR CaP.
Urine calcium went up in patients with calcium stones, no change in oxalate.

… and you might even dream (or fool yourself?) about achieving lower sodium intake in your patients, but the most likely explanation for the negative result of #NOSTONE, is just that: Thiazides do not work very well in preventing recurrent kidney stones. 2/2

I’m biased (local PI, steering committee), but the quality of #NOSTONE far exceeds most (if not all) data that the critics base their many assumptions and beliefs on.
You can speculate about the additional effects of citrate or a different type or dose of diuretic, … 1/2

Acidosis and CKD journals.lww.com/cjasn/citati...
"Whether there will be a definitive, adequately powered trial of this inexpensive, fairly safe intervention in CKD is up to funding
agencies to decide"
Cardiology is doing large outcome trials with colchicine - why can we not do this with alkali ?