Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT

J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):350-359. doi: 10.1002/jpn3.12077. Epub 2023 Dec 11.

Abstract

Objectives: Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT).

Methods: This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months.

Results: Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms.

Conclusion: Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.

Keywords: ascites; hyponatremia; midodrine; plasma rennin activity; rennin angiotensin aldosterone system.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / prevention & control
  • Adolescent
  • Adult
  • Ascites / drug therapy
  • Ascites / etiology
  • Child
  • Humans
  • Hyponatremia* / complications
  • Hyponatremia* / drug therapy
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / surgery
  • Liver Transplantation* / adverse effects
  • Midodrine* / therapeutic use
  • Treatment Outcome

Substances

  • Midodrine