Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review

Abstract

ObjectiveTo compare the efficacy and safety of theophylline or aminophylline for prevention of acute kidney injury (AKI) in neonates and children.DesignSystematic review and meta-analysis with application of Grading of Recommendations, Assessment, Development and Evaluation system.Data sourcesPubMed/MEDLINE, Embase, Google Scholar and Cochrane renal group were searched from 1970 to May 2018.Eligibility criteriaRandomised clinical trials and quasi-randomised trials comparing the efficacy and safety of prophylactic theophylline or aminophylline for prevention of AKI in neonates and children were included. The primary outcomes were: incidence of AKI, serum creatinine levels and all-cause mortality.ResultsA total of nine trials were included in the qualitative synthesis. Six trials including 436 term neonates with birth asphyxia who received a single dose of theophylline were finally included in the meta-analysis. The pooled estimate showed 60% reduction in the incidence of AKI in neonates with severe birth asphyxia (RR: 0.40; 95% CI 0.3 to 0.54; heterogeneity: I2=0%) (moderate quality evidence), decrease in serum creatinine over days 2–5 (very low to low quality evidence) without significant difference in all-cause mortality (RR: 0.88; 95% CI 0.52 to 1.50; heterogeneity: I2=0%) (very low-quality evidence). A significant difference in the negative fluid balance, increase in GFR and decrease in urinary β2 microglobulin was seen in favour of theophylline.Conclusion and relevanceA single dose of prophylactic theophylline helps in prevention of AKI/severe renal dysfunction in term neonates with severe birth asphyxia (moderate quality evidence) without increasing the risk of complications and without affecting all-cause mortality (very low-quality evidence).Trial registration numberCRD 42017073600.