Daishi Hirano1, Saori Miwa2, Daisuke Kakegawa2, Chisato Umeda2, Yoichi Takemasa2,3, Ai Tokunaga2, Kawakami Yuhei2, Akira Ito2. 1. Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-0003, Japan. bqx1976@hotmail.com. 2. Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-0003, Japan. 3. Division of Nephrology, Saitama Children's Medical Center, Saitama, Japan.
Abstract
BACKGROUND: The association of long-term acute kidney injury (AKI) risk with angiotensin-converting enzyme (ACE) inhibitor use in neonates/infants is poorly understood. We examined this association to identify potential AKI risk factors. METHODS: We retrospectively evaluated 119 children aged < 2 years (72 boys; median age, 5.0 months) who received ACE inhibitors for congenital heart disease for ≥ 6 months between January 2009 and June 2019. We monitored the occurrence of AKI, defined according to the Kidney Disease Improving Global Outcomes guidelines. Demographic and clinical data were extracted from medical records. Risk factors associated with AKI onset were identified by a Cox proportional hazards regression analysis of variables previously identified as risk factors of AKI and those significant in a univariate analysis. RESULTS: Thirty-three of 119 patients (28%) developed AKI at a median follow-up of 1.3 years (interquartile range, 0.8-3.2 years). AKI incidence was 1257 events per 10,000 patient-years. Concomitant tolvaptan use (hazard ratio [HR], 3.81; 95% confidence interval [CI], 1.82-7.97; P < 0.01) and Down syndrome (HR, 3.22; 95% CI, 1.43-7.29; P < 0.01) were identified as independent risk factors of AKI onset. CONCLUSIONS: AKI was strongly associated with concomitant tolvaptan use and Down syndrome in our study population. Physicians should consider these factors when prescribing ACE inhibitors for neonates/infants. Low-dose ACE inhibitors slow CKD progression because of their antifibrotic properties. ACE inhibitors may be beneficial for patients with Down syndrome who have underlying CKD in a non-acute setting. Therefore, they should be administered to such patients with caution.
BACKGROUND: The association of long-term acute kidney injury (AKI) risk with angiotensin-converting enzyme (ACE) inhibitor use in neonates/infants is poorly understood. We examined this association to identify potential AKI risk factors. METHODS: We retrospectively evaluated 119 children aged < 2 years (72 boys; median age, 5.0 months) who received ACE inhibitors for congenital heart disease for ≥ 6 months between January 2009 and June 2019. We monitored the occurrence of AKI, defined according to the Kidney Disease Improving Global Outcomes guidelines. Demographic and clinical data were extracted from medical records. Risk factors associated with AKI onset were identified by a Cox proportional hazards regression analysis of variables previously identified as risk factors of AKI and those significant in a univariate analysis. RESULTS: Thirty-three of 119 patients (28%) developed AKI at a median follow-up of 1.3 years (interquartile range, 0.8-3.2 years). AKI incidence was 1257 events per 10,000 patient-years. Concomitant tolvaptan use (hazard ratio [HR], 3.81; 95% confidence interval [CI], 1.82-7.97; P < 0.01) and Down syndrome (HR, 3.22; 95% CI, 1.43-7.29; P < 0.01) were identified as independent risk factors of AKI onset. CONCLUSIONS: AKI was strongly associated with concomitant tolvaptan use and Down syndrome in our study population. Physicians should consider these factors when prescribing ACE inhibitors for neonates/infants. Low-dose ACE inhibitors slow CKD progression because of their antifibrotic properties. ACE inhibitors may be beneficial for patients with Down syndrome who have underlying CKD in a non-acute setting. Therefore, they should be administered to such patients with caution.
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