EARLY CAREER EDITORIAL
Acute Kidney Injury in Neonates with Cardiac Disease: How Can We Care for the Smallest Among Us?
Tara M. Neumayr, MD
Assistant Professor of Pediatrics
Washington University School of Medicine/St. Louis Children’s Hospital
Division of Pediatric Critical Care Medicine and Division of Pediatric Nephrology
St. Louis, MO
Our appreciation of the significance of acute kidney injury (AKI) in critically ill patients represents important progress in our understanding of organ crosstalk and informs our care of pediatric patients after cardiac surgery and in the presence of cardiogenic shock, heart failure, systemic infections, and exposure to nephrotoxins. Each of these clinical scenarios gives rise to a particular pathophysiologic pattern of renal injury that may subtly alter the course of therapy, but the strongly negative impact of AKI of any type on mortality and other important clinical outcomes is an urgent and on-going challenge for cardiac intensivists. At the bedside of our littlest patients, in particular, we often find more questions than answers in the diagnosis and management of neonatal AKI.
Diagnosis of AKI is especially challenging in neonates with cardiac disease for a number of reasons. In all neonates, the transition from fetal to postnatal life involves two major changes in renal physiology. First, fetal renal circulation is notable for high renal vascular resistance (RVR) in association with low mean arterial blood pressure (MAP), resulting in very low renal blood flow (RBF) and glomerular filtration rate (GFR); at birth, MAP rises sharply, and RVR begins to fall such that the first several weeks of life are typically defined by a dramatic rise in RBF and, consequently, in GFR. Normal GFR in a term neonate is around 20 ml/min/1.73 m2 and doubles in the first two postnatal weeks; adult levels of RBF are not reached until approximately two years of age. It is easily apparent how alterations in anatomy and/or the neurohormonal axis – whether related to the need for cardiopulmonary bypass (CPB) or to some other alteration in effective RBF – can influence this process, preventing or delaying the expected increase in GFR over time.
The second major change that occurs at birth is that the neonatal kidney must take on the entirety of the filtration functions that were predominantly managed by the placenta during fetal life. Initial creatinine measures, therefore, are reflective of maternal filtration function rather than that of the neonate and only come to reflect the GFR of the neonate over the course of several weeks. Thus, creatinine, which performs imperfectly at all times and more so during times of rapidly changing GFR, for which it is meant to be a surrogate, is particularly ill-suited to describe renal function in critically ill neonates with cardiac disease in the face of the medical and surgical challenges posed by their care needs.
Fortunately, new tools for the diagnosis and management of neonatal AKI have gathered steam in recent years. Much of the initial work on identifying novel kidney injury biomarkers – including NGAL, KIM-1, IL-19, and L-FABP – was done in infants after CPB, and that work has helped us to better understand the potential utility of these biomarkers as well as to better appreciate the timing and nature of AKI in this population in general.
At this time, however, those assays have not yet gained widespread clinical use, and – for all its imperfections – serum creatinine and clinical assessments of urine output (UOP) have remained the mainstays of AKI diagnosis in many centers. The development of the neonatal KDIGO (Kidney Diseases: Improving Global Outcomes) criteria therefore represents a significant step forward, establishing the use of a “reference creatinine” (the lowest creatinine previously measured in a particular patient) from which assessments of decline in renal function may be made in concert with changes in UOP. AKI scoring systems like the renal angina index (RAI) and the fluid overload kidney injury score (FOKIS), while potentially powerful tools in critically ill patients, have thus far not been validated in neonates.
Management of neonatal AKI in cardiac patients remains a difficult undertaking, with fluid management, avoidance of nephrotoxins, and judicious use of peritoneal dialysis still the primary considerations, but a few new developments deserve mention here. First, the development of the furosemide stress test (FST) provides a structured way of assessing diuretic responsiveness, enabling the intensivist to give early consideration to alternative means of fluid management. Additionally, the introduction of renal replacement therapy (RRT) devices that are designed for neonates and/or feature low extracorporeal circuit volumes such as CARPEDIEM, Nidus, and Aquadex, if approved and widely available, hold forth the hope for delivery of RRT in this population with a high degree of fidelity and safety.
Pediatric cardiac intensive care has been at the forefront of much of the progress in diagnosis and management of neonatal AKI in recent years. It is my hope and belief that we will continue to lead in this area and, by so doing, will radically alter the care and recovery of our smallest and most vulnerable cardiac patients.