ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO478

Overall and Interindividual Effect of Four Different Drug Classes on Soluble Urokinase Plasminogen Activator Receptor in Albuminuric Type 1 and Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Rotbain Curovic, Viktor, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Houlind, Morten Baltzer, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
  • Kroonen, Marjolein, University Medical Center Groningen, Groningen, Netherlands
  • Jongs, Niels, University Medical Center Groningen, Groningen, Netherlands
  • Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Zobel, Emilie, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Tavenier, Juliette, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
  • Eugen-Olsen, Jesper, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
  • Laverman, Gozewijn Dirk, Ziekenhuisgroep Twente, Almelo, Overijssel, Netherlands
  • Persson, Frederik, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark
  • Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands
Background

Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker active in multiple inflammatory processes and a risk factor of diabetic nephorpathy. We evaluated the effect of four different drug classes on suPAR in type 1 and type 2 diabetes with albuminuria.

Methods

Post hoc analyses of a randomized, open-label, crossover trial including 26 adults with type 1 and 40 with type 2 diabetes with urinary albumin-creatinine ratio (UACR) ≥30 and ≤500 mg/g assigned to 4-week treatments with telmisartan 80mg, empagliflozin 10mg, linagliptin 5mg, and baricitinib 2mg separated by 4-week washouts. Plasma suPAR was measured before and after each treatment. SuPAR change after each treatment was calculated and, for each individual, the best suPAR-reducing drug was identified. Subsequently, the effect of the best individual drug was compared against the mean of the other three drugs. Repeated measures linear mixed-effects models were employed. Finally, treatment effect on UACR was correlated against treatment effect on suPAR, for each treatment and participant, assessed using Pearson's R.

Results

Baseline median (IQR) plasma suPAR was 3.5 (2.9, 4.3) ng/ml. No overall effect on suPAR levels was observed for any one drug. The individual best-performing drug varied, with baricitinib being selected for 20 (30%) participants, followed by empagliflozin for 19 (29%), linagliptin for 16 (24%), and telmisartan for 11 (17%). The individual best-performing drug reduced suPAR by 13.3% (95%CI: 3.7, 22.8; p=0.007). Difference in suPAR response between the individual best-performing drug and the other three was -19.7% (-23.1, -16.3; p<0.001). Baseline levels of suPAR and UACR were significantly correlated (R=0.28, p=0.029), but changes in UACR and suPAR after treatment were not correlated for any drug.

Conclusion

We demonstrated no overall effect of 4-week treatment with telmisartan, empagliflozin, linagliptin, or baricitinib on suPAR. However, individualization of treatment might significantly reduce suPAR levels and this mechanism is independent of UACR response.

Funding

  • Private Foundation Support