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

Objective To compare the efficacy and safety of theophylline or aminophylline for prevention of acute kidney injury (AKI) in neonates and children. Design Systematic review and meta-analysis with application of Grading of Recommendations, Assessment, Development and Evaluation system. Data sources PubMed/MEDLINE, Embase, Google Scholar and Cochrane renal group were searched from 1970 to May 2018. Eligibility criteria Randomised 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. Results A 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: I 2 =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: I 2 =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 relevance A 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 number CRD 42017073600.