Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers?

Abstract

Purpose

The syndrome of inappropriate antidiuresis (SIAD) is the main cause of hyponatremia and the SGLT2-inhibitor empagliflozin is a promising new treatment option. A biomarker predicting treatment response could optimize treatment success.

Materials and methods

Secondary analysis of a trial including 84 hospitalized patients with SIAD-induced hyponatremia. Patients were randomized to four days of treatment with empagliflozin 25 mg/d (n = 43) or placebo (n = 41) with both groups receiving fluid restriction <1000 ml/d. Baseline levels of copeptin, the natriuretic peptides MR-proANP and NT-proBNP and C-reactive protein (CRP) were evaluated as predictors for treatment response defined as absolute sodium change, using linear regression models. Additionally, urinary sodium was assessed as predictor for non-response to fluid restriction alone by constructing the receiver-operating characteristic (ROC) curve.

Results

No clinically relevant predictive value for treatment response to empagliflozin could be found for copeptin, MR-proANP, NT-proBNP or CRP. A urinary sodium cut-off of >76 mmol/l led to a specificity of 91.7% [95% confidence interval (CI): 75%, 100%] and sensitivity of 51.9% [33.3%, 70.4%] to predict non-response to fluid restriction alone.

Conclusions

Based on our data, no biomarker could be identified as predictor for treatment response to empagliflozin. Urinary sodium was confirmed as a good marker for non-response to fluid restriction in SIAD patients. Clinical trial registration: ClinicalTrials.gov (Number: NCT02874807)

Keywords:

• Copeptin
• C-reactive protein
• hyponatremia
• inappropriate ADH syndrome
• natriuretic peptides
• sodium-glucose transporter 2 inhibitors

Acknowledgements

The authors thank all patients for their participation in our study. In addition, we thank the laboratory personnel at the University Hospital Basel for their contribution to the study. A special thanks goes to our study nurses Cemile Bathelt, Nina Hutter and Joyce Santos de Jesus for their invaluable support.

Disclosure statement

The authors report no conflicts of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the Swiss National Science Foundation under Grant SNF-162608 as well as the University Hospital Basel. Thermo Scientific Biomarkers, Hennigsdorf, Germany (formerly B.R.A.H.M.S AG), sponsored the assay kits for copeptin and MR-proANP testing free of charge.