Pediatric acute kidney injury is a condition that is underdiagnosed among children seen in the emergency department, and it has been associated with significant morbidity and mortality, including increased risk for chronic kidney disease. The most common etiologies in pediatric patients are now known to be due to hypovolemia, sepsis, shock, and cardiac dysfunction. This issue compares 3 classification systems for the diagnosis and staging of acute kidney injury and reviews the etiologies that lead to kidney injury in children. The management of pediatric acute kidney injury focuses on identifying patients at high risk, monitoring intravascular volume status, avoiding nephrotoxic medication exposure, and involving a pediatric nephrologist once acute kidney injury is diagnosed.
An otherwise-healthy 3-year-old girl presents to the ED. According to the child’s mother, her daughter has been vomiting after meals for 3 days and has had 5 episodes of nonbloody, liquid diarrhea today. The mother also states that the girl drank only 4 oz of juice and 4 oz of water yesterday and would only drink half as much today. The girl has urinated only once today. She is afebrile, with a heart rate of 145 beats/min and a blood pressure of 80/30 mm Hg. On examination, the girl appears tired, has dry mucous membranes, and a capillary refill time of 3 seconds. She has diffuse abdominal tenderness but no costovertebral angle tenderness and no rash.
In the next room, a 16-year-old adolescent boy who was diagnosed with osteosarcoma 4 months ago and recently underwent treatment with cisplatin has presented with 1 day of diffuse abdominal and back pain associated with nausea, vomiting, and a decrease in oral intake and urine output.
Which historical or physical examination findings in these patients would warrant an evaluation for acute kidney injury? Which laboratory tests or imaging would be most useful in the diagnosis of these patients? How should the risk of kidney injury affect your medical management of these patients?
Acute kidney injury (AKI) refers to a sudden loss of kidney function resulting in a decline in the glomerular filtration rate (GFR) and a reduced capacity to excrete nitrogenous waste and regulate extracellular volume and electrolytes. AKI is an increasing problem in children as the medical care being administered becomes increasingly complex. An initial report of hospitalization data revealed an AKI diagnosis in 3.9 per 1000 hospitalized patients; however, the true incidence may be higher, as most diagnostic criteria rely on knowledge of a patient's baseline creatinine level.1-4 While the incidence of AKI is higher among children who are hospitalized or in the intensive care unit (ICU), the incidence among children presenting to the emergency department (ED) is unclear.5 In one surveillance study, only 18.5% of pediatric patients who had AKI during hospitalization were diagnosed in the ED, with the majority developing AKI after admission.6
The true incidence of pediatric AKI (pAKI) is partly unknown due to the lack of consensus regarding the definition of pAKI and the lack of prospective data. However, available studies suggest that pAKI is slightly more prevalent among boys than girls (1.3:1) and among black patients as compared with other races.1 Previously, the most common causes of pAKI in hospitalized patients were thought to be hemolytic uremic syndrome, glomerulonephritis, and primary renal pathology. More recent data have identified sepsis, surgery for congenital heart disease involving cardiopulmonary bypass, nephrotoxic drug exposure, and oncologic illness as having the highest association with pAKI.7 With these other associated disease processes, pAKI diagnosis and management may be overlooked in the ED setting.
Beyond the potentially worsening acute clinical processes taking place, pAKI may also be a risk factor for chronic kidney disease (CKD),3 which affects 26 million Americans and is responsible for over $40 billion of Medicare payments annually.8 Previously, AKI was thought to be a transient and reversible process; however, animal studies have shown that episodes of AKI can cause a permanent reduction in peritubular capillaries, predisposing a patient to further renal hypoxia, inflammation, and eventually fibrosis.9 In a retrospective meta-analysis of 346 pediatric patients, Greenberg et al demonstrated a high rate of proteinuria, hypertension, decreased GFR, and mortality after pAKI; however, the primary studies in this systemic review were small and lacked control groups.4 Pediatric emergency clinicians may have an opportunity to provide immediate treatment for pAKI, and, in doing so, may mitigate potential long-term effects.
This issue of Pediatric Emergency Medicine Practice focuses on the recently constructed definitions of AKI, the array of diagnoses that are associated with its development, and the management of these patients in the ED setting.
The available literature on pAKI and its management was reviewed in PubMed using the search terms acute kidney injury, acute kidney injury management, acute renal failure, kidney failure, renal insufficiency, renal vein thrombosis, prerenal failure, and obstructive renal failure. The search was limited to studies of patients from birth to age 18. Abstracts were reviewed for relevance to the topic, and cited articles within the search results were also considered. Articles that primarily focused on neonatal intensive care or cardiac surgery patient populations were excluded.
The current literature on pAKI includes few high-powered prospective controlled trials, with a greater volume of retrospective data, case reports, and adult studies. Many of the existing pediatric studies are limited by small sample size and a primary focus on ICU patients or those requiring dialysis.10 The greatest limitation is the lack of a single unified classification system; prior to 2004, over 30 definitions of AKI existed in the literature, making cohort analyses virtually impossible.11
1. “The rise in creatinine was minimal and the patient was classified in the Risk category of AKI. There was no need to consult nephrology, since this category does not lead to any longterm consequences.”
AKI is not a static process, but can progress throughout the course of a patient’s illness based on the etiology and the management they receive. Thus, AKI in a patient who is in the Risk stage that is not caught early could continue to progress to worsening stages, particularly if the patient has a serious illness, such as sepsis. When AKI is identified, a nephrology consult should be considered, as all patients may be at risk for long-term consequences and should have follow-up even when ”recovered.”
2. “I checked that patient’s creatinine, and the result was within the normal range, so I ruled out AKI.”
While the creatinine level is typically used as a screening tool to diagnose AKI, it is not always a reliable indicator in children. This is due to the relatively low levels of creatinine in children as compared to adults, and the wide range of normal values for different age groups. Since many children do not have baseline values of creatinine available as a reference point, it is difficult to assess the degree of change based on a measurement at a single point in time.
3. “Muscle aches associated with viral infections are a benign symptom and are not associated with AKI.”
While myalgias are a common complaint associated with viral infections, emergency clinicians should consider viral myositis in their differential as well. In this case, muscle breakdown could lead to rhabdomyolysis and cause AKI. Other causes of rhabdomyolysis include exertion and traumatic crush injuries.
4. “Mannitol is an osmotic diuretic. It improves a patient’s urine output, and, thus, renal function. That’s why it is the best treatment option for AKI.”
While osmotic diuresis facilitated by mannitol can correct a patient’s oliguria, there is no evidence to support the use of mannitol in the prevention or management of AKI. In fact, the administration of mannitol may worsen AKI by causing or worsening nephropathy. This is also true of other diuretics, which should only be used in the setting of volume overload.
5. “Since I didn’t have a baseline creatinine value to compare to my current creatinine level, I ordered a renal ultrasound to determine whether AKI is present.”
Renal ultrasonography is considered the first diagnostic imaging modality of choice for AKI; however, it cannot identify whether AKI is present. In patients with CKD, small kidney size may be noted on ultrasound and may be an indication that the elevated creatinine is not from an acute process. Similarly, in postrenal AKI, the ultrasound may demonstrate hydronephrosis as a cause of elevated creatinine. However, in patients with intrinsic renal disease, the ultrasound may be normal or show enlarged, echogenic kidneys, but this does not distinguish between acute and chronic disease.
6. “The patient’s creatinine did not increase much compared to a prior value in her medical record, so she cannot have AKI.”
Although a rise in creatinine is used in all of the classification systems to define AKI, it is not the most sensitive or reliable test. Creatinine may not rise until up to 50% of the patient’s glomerular filtration is lost, and may not increase during the first 24 to 48 hours of disease, thus delaying the ability of this test to identify patients with AKI.
7. “The patient with AKI was tolerating oral fluids, so I did not consider the need for expedited volume repletion with IV fluids.”
While oral rehydration is often the first-line choice for management of mild dehydration in children, it may be insufficient in the setting of AKI. Moderate-to-severe dehydration, elevated creatinine levels, and decreased urine output should prompt the provider to consider IV fluid replacement therapy. Prompt administration of IV isotonic fluids may improve renal perfusion and lessen further kidney damage. Urine output should be monitored carefully in this setting.
8. “Ibuprofen is a benign medication, and its use in patients is always appropriate.”
Ibuprofen is a commonly administered medication to address pain and/or fever. However, ibuprofen can also cause AKI. The history should include questions regarding a patient’s previous use of ibuprofen, as this is an identifiable risk factor for AKI. The use of ibuprofen should be avoided if it is unnecessary, particularly in a dehydrated patient. After controlling for the degree of dehydration, ibuprofen exposure increased the risk of AKI more than 2-fold in this setting, and concomitant use of ibuprofen and acetaminophen further increased the risk of developing AKI. Therefore, ibuprofen use should be avoided in any child suffering from acute gastroenteritis or other illnesses that may predispose them to hypovolemia.
9. “The urinalysis was negative, so there was no evidence of kidney injury.”
Similar to creatinine, a urinalysis may provide helpful information about the kidneys and their function; however, it is not a useful screening test for AKI. Nonetheless, positive findings on urinalysis may be helpful in the differential diagnosis. The presence of leukocyte esterase or nitrites may indicate a urinary tract infection. The presence of hematuria may indicate nephritis, urolithiasis, trauma, viral cystitis, or myoglobinuria from rhabdomyolysis. The presence of red cell casts is diagnostic of glomerulonephritis. Persistent proteinuria may be an indicator of nephrotic syndrome, tubulointerstitial disease, or glomerular disease, whereas transient proteinuria may have a more benign etiology. The combination of hematuria and proteinuria should suggest a renal disease such as Alport syndrome, membranoproliferative glomerulonephritis, or IgA nephropathy.
10. “There was no evidence of kidney involvement because there was no abdominal pain, back pain, or costovertebral angle tenderness on examination.”
A high degree of suspicion is needed to diagnose AKI in children. There may be no indication from the history or physical examination that a renal problem is present. Pain is often not a presenting sign. Emergency clinicians must consider the risk of AKI when managing other acute problems in children such as dehydration, infection, trauma, drug intoxication, and medication administration.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. The most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.
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Daniel Mohrer, MD; Melissa Langhan, MD, MHS
May 2, 2017
June 1, 2020
4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits. Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 1 Pharmacology CME credit
Date of Original Release: May 1, 2017. Date of most recent review: April 15, 2017. Termination date: May 1, 2020.
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