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SGLT2 INHIBITORS IN ADTKD

Observational study: benefits questionable

13 October 2025 – Medical guidelines now recommend SGLT2 inhibitors as the new standard treatment for patients with chronic kidney disease (CKD). Several studies have demonstrated their benefits in terms of protecting against cardiovascular changes. They also have the potential to slow the progression of CKD and delay the onset of kidney failure. The benefits were particularly significant in kidney diseases associated with high protein loss in the urine (proteinuria). However, this is not the case with ADTKD. The results of a recent observational study from the USA reinforce these doubts.


SGLT2 inhibitors (sodium-glucose cotransporter 2 inhibitors) are drugs that were originally developed for the treatment of diabetes. They lower blood sugar by inhibiting the reabsorption of sugar in the kidneys, causing more glucose to be excreted in the urine. It is now known that they can also protect kidney and heart function in many forms of CKD.


There is currently no specific treatment for patients with autosomal dominant tubulointerstitial kidney disease (ADTKD). Researchers in the USA investigated whether SGLT2 inhibitors are safe for this condition and have a beneficial effect on kidney function.

The observational study was conducted in 27 individuals with genetically confirmed ADTKD (subtypes UMOD or MUC1). None of the participants had diabetes or protein in their urine. Changes in kidney function (eGFR) were compared before and after the start of SGLT2 inhibitor therapy and with a suitable control group (30 individuals without SGLT2 inhibitors).


Results

  • Twelve of the 27 individuals discontinued therapy within the first year, mostly due to the expected short-term decline in eGFR.
  • There were no serious side effects.
  • The average deterioration in kidney function was similar to that before the start of therapy or in comparison to the control group.
  • Neither the haemoglobin level nor the biomarkers for kidney damage (KIM-1) improved.
  • Overall, there was no clear benefit, but also no safety concerns.


The study's significance is limited. It was neither randomised nor placebo-controlled, the number of participants was small, and the observation period of about one year was relatively short. In addition, some of the participants discontinued the study prematurely.


Conclusion

SGLT2 inhibitors were well tolerated in ADTKD, but showed no measurable improvements in kidney function or laboratory values. The results suggest that SGLT2 inhibitors probably have no significant therapeutic effect in ADTKD.


Source:

Kidd Ko et al. An Observational Study of SGLT2 Inhibitors and Their Use in Autosomal Dominant Tubulointerstitial Kidney Disease. Res Sq [Preprint]. 25 September 2025:rs.3.rs-7482366.

https://pubmed.ncbi.nlm.nih.gov/41041531