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

Ren Fail. 2023 Dec;45(1):2194434. doi: 10.1080/0886022X.2023.2194434.

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 2nd received allopurinol, the 3rd group received linagliptin, and the 4th 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: DPP4Is; N-acetyl cysteine; Post-contrast AKI; allopurinol; linagliptin.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / therapeutic use
  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / prevention & control
  • Allopurinol* / administration & dosage
  • Allopurinol* / therapeutic use
  • Chemoprevention / methods
  • Contrast Media* / adverse effects
  • Diabetic Nephropathies* / classification
  • Diabetic Nephropathies* / complications
  • Diabetic Nephropathies* / diagnosis
  • Drug Therapy, Combination
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / diagnosis
  • Linagliptin* / administration & dosage
  • Linagliptin* / therapeutic use
  • Prospective Studies
  • Protective Agents* / administration & dosage
  • Protective Agents* / adverse effects
  • Protective Agents* / therapeutic use
  • Renal Insufficiency, Chronic / classification
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / diagnosis
  • Saline Solution / administration & dosage
  • Saline Solution / therapeutic use

Substances

  • Allopurinol
  • Linagliptin
  • Contrast Media
  • Acetylcysteine
  • Protective Agents
  • Saline Solution

Associated data

  • ClinicalTrials.gov/NCT03470454

Grants and funding

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