Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study

Abstract

Background

Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3–5 chronic kidney disease (CKD) patients with underlying DKD.

Methods

Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2^nd received allopurinol, the 3^rd group received linagliptin, and the 4^th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients.

Results

20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis.

Conclusion

Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view.

Trial registration ClinicalTrials.gov

NCT03470454

Keywords:

• Post-contrast AKI
• DPP4Is
• linagliptin
• allopurinol
• N-acetyl cysteine

Ethical approval

This material has not been published previously, in whole or part, and is not under consideration for publication elsewhere. This paper has no tables or figures that would require permission to reprint. The authors have no conflict of interest to declare. All authors participated in the preparation of this manuscript, fulfilled the criteria for authorship, and approved the paper in the current format. The study conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the prior approval by the institution’s human research committee. This study was not supported by any grant. The trial registration number at ClinicalTrials.gov was NCT03470454.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.