Acute Kidney Injury
Gangadarshni Chandramohan, MD, MSc, FASN, FAAP
A 10-month-old girl has a 2-day history of fever, vomiting, and watery diarrhea. The child has previously been healthy. Her diet has consisted of infant formula fortified with iron, baby food, and some table food. Since the onset of her illness, she has not been drinking or eating well, and she has thrown up most of what she has eaten. Her mother has tried to give her oral electrolyte solution and apple juice on several occasions but has had limited success. The child has had 8 to 10 watery stools without blood or mucus each day. Her temperature has varied between 37.0°C (98.6°F) and 38.8°C (101.8°F); the mother has given her daughter acetaminophen, which she has vomited up. The girl’s 4-year-old brother and her parents are doing well and have no vomiting or diarrhea.
The physical examination reveals a severely dehydrated (estimated amount 15%), listless infant. Her weight is 9.4 kg (20.7 lb), her height is 74 cm (29.1 in), her temperature is 38.4°C (101.1°F), her heart rate is 168 beats per minute, her respiratory rate is 30 breaths per minute, and her blood pressure is 72/40 mm Hg with an appropriately sized cuff. Capillary refill is 2 to 3 seconds. The skin appears dry, but no rash is present. Head and neck, chest, heart, and abdominal examinations are normal. Pending the results of her blood studies, an intravenous fluid bolus of 180 mL normal saline (20 mL/kg) over 20 to 30 minutes is administered. This is followed by 2 more boluses of 180 mL normal saline each. The girl is catheterized to obtain urine and determine the urine flow rate over the next several hours. A urinalysis is performed.
1. What are the 3 stages of acute kidney injury?
2. What is the etiology of acute kidney injury?
3. How would the physician assess a patient with acute kidney injury?
4. How would the physician manage a child with acute kidney injury?
5. What are the indications for renal replacement therapy?
Acute kidney injury (AKI) is encountered in outpatient and inpatient settings and is associated with a high rate of morbidity and mortality depending on the primary cause of the insult. Acute kidney injury is defined as a sudden decrease in kidney function, signified by the accumulation of nitrogenous waste products (ie, blood urea nitrogen [BUN] and various other metabolic waste products) and impaired balance of fluid and electrolytes. With a better understanding of the pathophysiology of acute deterioration in renal function, the term AKI delineates the process of renal injury and encompasses the full spectrum of renal dysfunction, from early, mild renal injury with only a small elevation in serum creatinine level, to severe kidney injury requiring renal replacement therapy (ie, dialysis) as a continuum.
To better delineate the progression of AKI, in 2004 the Acute Kidney Injury Network Acute Dialysis Quality Initiative workgroup set forth the RIFLE criteria, which is based on serum creatinine level and urine output. The acronym RIFLE defines 3 stages of progressively increasing severity of renal injury (risk, injury, and failure) followed by 2 outcomes variables (loss and end-stage renal disease). These criteria, proposed in 2004 and validated in 2012 by the Kidney Disease: Improving Global Outcomes (KDIEGO) AKI workgroup, modified RIFLE for the pediatric population (pRIFLE) and its clinical use has been shown to improve outcomes in children (Figure 81.1). This classification is based in part on declining urine output; however, some children experience nonoliguric renal failure, in which urine output may remain normal or even increase. Decline in urine output is an essential component of risk assessment when determining severity of AKI in the pediatric patient because of the known association between the duration of oliguria and increased mortality.
The pRIFLE criteria are not applicable to newborns during the first few days after birth, however, because they may exhibit physiological oliguria during the first 24 hours after birth and their serum creatinine level initially reflects maternal creatinine values. Therefore, the pRIFLE criteria were further modified for neonates based on findings from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, which set the baseline creatinine level as the lowest level based on gestational age and set the serum creatinine threshold for stage 3 AKI at greater than or equal to 2.5 mg/dL rather than greater than 4 mg/dL.
The pRIFLE classification is intended to emphasize the reversible nature of the renal insult, which often is present in critically ill children admitted to pediatric or neonatal intensive care units (ICUs). It is anticipated that this precise and universal definition of AKI likely will enable physicians to rapidly recognize at-risk individuals and intervene promptly to improve immediate and long-term outcomes. The major limitation to the use of this classification is that it is not validated in children who present with AKI in an outpatient setting, whose etiology and outcomes often are dissimilar to those of inpatient, acutely ill children.
Figure 81.1. Pediatric risk for renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal disease (pRIFLE) criteria to assess the stage of renal injury.
Abbreviations: eCrCl, estimated creatinine clearance.
Derived from Bellomo R, Ronco C, Kellum JA , Mehta RL, Palevsky P; ADQI Workgroup. Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204–R212 PMID: 15312219 doi.org/10.1186/cc2872.
Acute kidney injury occurs in children with a wide variety of medical or surgical conditions and especially in children who are critically ill. The exact incidence of AKI in children is unknown because it not plausible to capture all cases of AKI, particularly in children who present to outpatient settings. The prevalence of AKI varies depending on geographic and demographic factors, which are responsible for the etiology of AKI. In developed countries, AKI has been increasing over the past few decades because of the increasing number of cardiopulmonary bypass surgeries performed to manage congenital heart disease, an increase in the number of solid organ and bone marrow transplantations, and the use of newly discovered nephrotoxic agents to manage a variety of disorders. Acute kidney injury resulting from primary renal disease appears to be on the decline compared with AKI caused by other systemic illnesses or their treatments. Acute kidney injury is often observed in patients in the ICU with sepsis or major trauma with severe bleeding or in the postoperative period after major heart surgery. According to Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) data published in 2016, of 4,683 critically ill children, 26.9% developed AKI and 11.6% had severe AKI (stage 2 and 3). Approximate 5% to 10% of patients in neonatal ICUs develop AKI, and most commonly as the result of perinatal hypoxia and postnatal hypotension.
Most children with AKI initially present with clinical findings of the primary condition that ultimately results in the renal problem. In the critically ill child, a small increase in serum creatinine may be the first indication of AKI. However, decreased urine output, edema, hematuria, and/or hypertension may be the early sign or signs specifically related to declining renal function (Box 81.1). Additionally, hyperkalemia with cardiac arrhythmia, hyperventilation resulting from acidosis, and nausea and vomiting resulting from uremia may occur with progression of renal failure.
Etiology and Pathophysiology
Because of the recent epidemiologic shift from renal to nonrenal causes as common etiologic factors, for every child the primary care physician as well as the neonatal and pediatric intensivist should perform a risk assessment using the pRIFLE criteria and take the necessary steps to prevent AKI before the kidneys sustain serious injury. Frequently, the cause is multifactorial, and ischemic-hypoxic injury and nephrotoxic insults are important contributors; the pathophysiology of hypoxic ischemic injury and nephrotoxic insults is described herein.
The causes of AKI are usually grouped into 3 categories: prerenal, postrenal, and intrinsic renal disorders (Box 81.2 and Figure 81.2). Although prerenal failure and acute tubular necrosis (ie, intrinsic renal failure) may in fact be on opposite ends of a continuum, rather than separate entities, this classification system still aids in the conceptualization of the underlying problem and formulation of the initial treatment plan. Correspondingly, without timely intervention postrenal failure has the potential to cause renal damage and ultimately can result in intrinsic renal failure.
Prerenal disorders are the most common cause of AKI in pediatric patients and result in a decrease in total or effective circulating blood volume. An absolute decrease in circulating volume can be caused by blood loss from acute hemorrhage secondary to trauma or fluid loss and dehydration secondary to gastroenteritis. Heart failure or redistribution of body fluids (ie, third spacing) can result in decreased effective circulating volume. In each of these situations, the resulting decrease in the glomerular filtration rate (GFR) can be readily reversed by improving renal perfusion in its early stages. If hypoperfusion is prolonged, however, ischemic damage to the kidney occurs and intrinsic renal failure occurs.
In infancy and early childhood, urinary obstruction caused by posterior or anterior urethral valves or other congenital lesions involving the urinary tract can result in AKI. In the older child, kidney stones, pelvic trauma, or complications following pelvic surgery are possible causes of postrenal failure.
Box 81.1. Diagnosis of Acute Kidney Injury
•Decreased urine output
•Elevated serum creatinine level
•Blood urea nitrogen-creatinine ratio <20
•Elevated fractional excretion of sodium
Box 81.2. Etiology of Acute Kidney Injury in Children
•Decreased plasma volume
•Third spacing of plasma volume in the setting of burns, sepsis, bowel obstruction
•Other causes of renal hypoperfusion
•Congestive heart failure
•Bilateral renal artery stenosis
•Bilateral ureteropelvic or ureterovesical junction obstruction
•Posterior urethral valves
•Trauma to urethra
•Obstruction caused by kidney stone at the bladder neck or stone obstruction of both urinary tracts
Intrinsic Renal Disorders
•Vascular: renal artery or vein thrombosis, disseminated intravascular coagulation.
•Glomerular: hemolytic uremic syndrome, severe (ie, rapidly progressive) glomerulonephritis from any etiology.
•Interstitial: interstitial nephritis resulting from allergic reaction to drugs (eg, nonsteroidal anti-inflammatory drugs, oxacillin, methicillin), sepsis.
•Tubular (acute tubular necrosis): sepsis, postcardiac surgery, ischemia resulting from prolonged hypoperfusion; all causes listed in prerenal category, if sufficiently prolonged, may lead to acute tubular necrosis.
•Nephrotoxins: aminoglycoside antibiotics, indomethacin, radiocontrast agents, ethylene glycol, methanol, heavy metals.
•Pigments: myoglobinuria, hemoglobinuria.
•Uric acid: hyperuricemia, tumor lysis syndrome.
•Congenital renal anomalies (especially in newborns and young infants).
•Bilateral cystic dysplastic kidneys, reflux nephropathy, polycystic kidneys, oligomeganephronia.