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Journal of Neonatal-Perinatal Medicine 6 (2013) 179–181 DOI 10.3233/NPM-1366012 IOS Press

Case Report

Enalapril-induced acute kidney injury in neonates A. Russoa,∗ , A. Miranib , J. Perlmana and S. Millera a Division b Division

of Newborn Medicine, New York Presbyterian Hospital Weill Cornell, NY, USA of Pediatric Cardiology, New York Presbyterian Hospital Weill Cornell, NY, USA

Received 13 October 2012 Revised 09 January 2013 Accepted 28 January 2013

Abstract. Angiotensin converting enzyme inhibitors have been used in the neonatal population for both cardiac and renal diseases. Past reports have described deleterious renal and neurological consequences as a result of these drugs. This report describes two infants receiving enalapril for different indications who suffered renal impairments, likely a result of concomitant diuretic use. These cases demonstrate the risks associated with ACE inhibitor use and the importance of vigilant monitoring when using these medications. Keywords: Hypotension, ACE inhibitors, oliguria, congestive heart failure

1. Introduction Angiotensin Converting Enzyme (ACE) Inhibitors, such as enalapril, are used for renal and cardiovascular diseases in adult and pediatric patients. In infants with cardiomyopathy, ACE inhibitors are used as firstline therapy in order to achieve afterload reduction as well reduce catecholamine drive [1]. The action is to block the conversion of angiotensin I to angiotensin II thereby lowering arteriolar resistance and increasing venous capacity. This effectively decreases left ventricular afterload resulting in improved cardiac ejection [2]. The side effects of impaired renal function and potassium retention are well known in adults and may be due to decreased renal perfusion secondary to hypotension, decreased filtration fraction and a direct ∗ Corresponding

author: Dr. Anne Russo, Division of Newborn Medicine N 506, New York Presbyterian Hospital, 525 East 68th Street, NY 10065, New York, USA. Tel.: +1 212 746 3530; E-mail: [email protected].

nephrotoxic effect [2–4]. There is some literature, primarily limited to case reports, on the consequences of neonatal enalapril administration [2–4]. The following are two cases of infants in congestive heart failure (CHF) administered enalapril for different indications who suffered similar adverse effects and are reported to highlight the potential for renal injury in this population.

2. Case 1 A 3.005 kg term male was born with transposition of the great vessels with a ventricular septal and atrial septal defect. On day of life (DOL) 5 he underwent cardiac repair. Post-operatively, he was managed on furosemide and aldactone for diuresis. Oral enalapril (0.05 mg/kg/dose) was added on post-operative day (POD) 11 for afterload reduction due to echocardiographic evidence of cardiac dysfunction. On POD 13,

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Fig. 1. Creatinine concentrations for case one (series 1) and case two (series 2) prior to, during and after enalapril use. Note the peak in creatinine which occurs after enalapril is discontinued. Case one ; Case two

after receiving 5 doses of oral enalapril, he became acutely hypotensive and oliguric. Urine output trended from an average of 4 ml/kg/day to 1.6 ml/kg/day and eventually, to 0.1 ml/kg/day. His weight at this time was 2.94 kg, 65 g below birth weight. The enalapril and furosemide were discontinued and he was given a 10 ml/kg infusion of normal saline without improvement in the clinical status. A basic metabolic panel showed a Blood Urea Nitrogen (BUN) of 19 mg/dL and creatinine 1.35 mg/dL, which were up from 13 mg/dL and 0.77 mg/dL twelve hours prior, (Fig. 1). He received additional fluid boluses and was started on an intravenous injection of dopamine at a dose of 5 mcg/kg/min for hypotension. Mean blood pressures improved from low 30 s to 40–50 s. The creatinine peaked at 1.73 mg/dL on POD 14. A renal ultrasound was normal and blood cultures were negative. By POD 16, he was weaned off dopamine with mean arterial blood pressures (MAP) of 50–60 mmHg and return of normal urine output and renal function. He progressed favorably and eventually was discharged home on POD 34 with no long-term adverse renal consequences.

3. Case 2 A 1635 gram male born at 32 5/7 weeks gestation was born with VACTERL sequence involving congenital heart disease, tracheoesophageal fistula, and duodenal atresia. He underwent cardiac repair at one month of age at 2260 grams. One month later, while receiving chlorothiazide 10 mg/kg/dose twice daily

and furosemide 1 mg/kg/dose twice daily, he developed nephrotic range proteinuria despite normal renal function and a normal renal ultrasound. He was started on oral enalapril for proteinuria with an initial dose of 0.05 mg/kg. He had a transient decrease in MAP (from mid 50 s to 40 s) with the initial dose but this improved without intervention. The subsequent two doses were given intravenously (IV) with doses of 0.01 mg/kg and 0.005 mg/kg on day 2 and 3, respectively. Following the second IV dose, the infant developed an acute episode of hypotension (MAPs 30 mmHg). Oliguria followed and he had minimal response to fluid boluses. Enalapril, furosemide and chlorothiazide were discontinued and he was treated with dopamine. An echocardiogram demonstrated normal left ventricular systolic function. BUN and Creatinine rose to 57 and 0.77 mg/dL, respectively on the day of the hypotensive episode and peaked at 74 and 0.8 mg/dL one day later (Fig. 1). Creatinine and urine output normalized 48 hours later. He received no further doses of enalapril and ultimately succumbed to progressive pulmonary hypertension and respiratory failure about six weeks later.

4. Discussion In utero, the placenta rather than the kidneys, acts as the main excretory organ. Fetal renin and angiotensin II concentrations are greater than postnatal values resulting in high renal vascular resistance and decreased renal blood flow [2, 4]. Postnatally, these levels slowly decline to allow more renal blood flow as the kidney assumes a more active role in excretion. Whereas adult kidneys receive 20–25% of cardiac output, fetal kidneys receive 3–4% which increases to 8–10% in the first postnatal week and approach adult levels by age 2 years [2, 3]. Therefore, newborns are sensitive to alterations in renal blood flow, particularly when exposed to conditions such as hypoxemia or ACE inhibitors [2]. There is extensive evidence that antenatal ACE inhibitor use is associated with renal dysfunction [3]. Many case reports describe the adverse effects of ACE inhibitors in neonates [3–7]. Dutta [3] described a 2.75 kg 37 week gestation infant who received oral enalapril on DOL six for CHF. The infant became oliguric and ultimately anuric, requiring peritoneal dialysis for twenty days. Gantenbein [4] retrospectively studied forty-three infants who received captopril in addition to diuretics for the treatment of CHF. Side effects,

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including reversible renal failure and hypotension, were seen in seventeen (39%) of those patients. The infants in our cases suffered acute kidney injury (AKI) following the administration of enalapril in conjunction with diuretics. We postulate that this combination compounded the effects on the kidneys and resulted in oliguric AKI secondary to hypotension-induced inadequate renal blood flow. This vulnerability may be increased in the post operative cardiac situation.

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Financial disclosure statement The authors have no financial relationships relevant to this article to disclose.

Conflict of interest The authors have no conflicts of interest to disclose. References

5. Conclusion [1]

Currently, enalapril is approved by the Food and Drug Administration for the management of mild to severe hypertension (ages 1 month to adults), CHF (adults), and asymptomatic left ventricular dysfunction (adults) [8]. The use in newborns is off label for both cardiac and renal etiologies. Despite case reports outlining the potential serious consequences of ACE inhibitors, these drugs continue to be prescribed in the neonatal population [9]. Physicians need to be aware of the these potential side effects, particularly in a situation of CHF and that close monitoring of urine output, blood pressure and renal function is critical. Although ACE inhibitors may ultimately need to be used to treat CHF, physicians should be encouraged to start with alternative therapies, such as digoxin, which have been more extensively studied and have a more desirable safety profile [8].

[2] [3] [4]

[5]

[6]

[7] [8] [9]

Rosenthal D. Cardiomyopathy in Infants: A brief overview. NeoReviews 2000;1:139-45. Su S, Stonestreet B. Core concepts: Neonatal glomerular filtration rate. NeoReviews 2010;11:714-21. Dutta S, Narang A. Enalapril-induced acute renal failure in a newborn infant. Pediatr Nephrol 2003;18:570-72. Gantenbein M, Bauersfeld U, Baenziger O, Bernhard F, Neuhaus T, Sennhauser F. et al., Side effects of angiotensin converting enzyme inhibitor (Captopril) in newborns and young infants. J Perinat Med 2008;36:448-52. Wood E, Bunchman T, Lynch R. Captopril-Induced Reversible acute renal failure in an infant with coarctation of the aorta. Pediatrics 1991;88:816. Tack ED, Perlman JM. Renal Failure in sick hypertensive premature infants receiving captopril therapy. J Pediatr 1988;112:805-10. Perlman JM, Volpe JJ. Neurologic complications of captopril treatment of neonatal hypertension. Pediatrics 1989;83:47-52. Lexi-Comp OnlineTM , Pediatric & Neonatal Lexi-Drugs OnlineTM , Hudson, Ohio: Lexi-Comp, Inc.; January 29, 2011. Kazuo M. ACE Inhibitors in pediatric patients with heart failure. Pediatr Drugs 2006;1:55-69.

Enalapril-induced acute kidney injury in neonates.

Angiotensin converting enzyme inhibitors have been used in the neonatal population for both cardiac and renal diseases. Past reports have described de...
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