Acute renal failure (ARF) is the sudden decline in renal function resulting in increase in metabolic waste products in the blood and dysregulation of extracellular electrolytes and volumes. This is usually marked by elevations in serum creatinine and increased, normal, or decreased urine output. The terms polyuria, oliguria, and anuria sometimes are used to characterize the type of failure. The term acute kidney injury (AKI) has replaced acute renal failure in the literature in an effort to better characterize the spectrum of impairment in renal function before complete failure.

In order to better characterize the spectrum of acute kidney injury or renal failure, two classification systems were developed to standardize assessment of acute kidney injury for clinical and research purposes. Both use creatinine and urine output criteria to stratify renal injury (Table 110-1). The AKIN criteria were developed by the Acute Kidney Injury Network and consist of three stages. AKIN classification has not been validated in children and does not capture milder cases of acute renal injury.¹ The other system, called pRIFLE, was developed by modifying existing adult RIFLE criteria. pRIFLE consists of categories of increasing severity: Risk, Injury, Failure, Loss, and End Stage Renal Disease.^2,3

Traditionally, elevated serum creatinine is used to make the diagnosis of renal failure. This is problematic for several reasons. Serum creatinine is an isolated measurement and does not accurately reflect ongoing changes in renal function. Creatinine takes time to accumulate so an early normal value may not reflect ongoing and potentially severe injury. In children, it is even more difficult as often the baseline creatinine level for a patient is not known and a rise from the baseline may still fall within the “normal” range for lab values. Additionally, once dialysis is started creatinine is no longer helpful in assessing renal function.

Given the limitations of creatinine measurement in accurately diagnosing early renal injury and the improved outcomes in early treatment of renal injury, much research is now focused on biomarkers. The most promising biomarkers of renal injury in urine and blood are neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin-18 (IL-18).^4,5 Continued work in this area may provide clinically useful assays that result in earlier diagnosis and treatment of renal injury.

PATHOPHYSIOLOGY

Impairment in renal function can occur for a variety of reasons and is often multifactorial in hospitalized children. Kidney damage can result from impairment in blood flow, direct damage to the filtration system itself or by increased pressure on the filtration system by impaired output. The classic names for these categories are prerenal, intrinsic, and postrenal (Table 110-2).^6,7 Prerenal causes all result in decreased renal perfusion leading to decreased glomerular perfusion and filtration with subsequent elevation of blood urea nitrogen and creatinine. Examples include dehydration, septic shock, and heart failure. Intrinsic causes are a larger more varied group as any cause of direct damage to the filtration function of the kidney is included. These include vascular, tubular, interstitial, and glomerular processes. Acute tubular necrosis, nephrotoxins, HUS, and primary renal diseases are included as they result in direct damage to the glomeruli or renal tubule. Iatrogenic administration of nephrotoxic medications is the fastest growing cause of renal injury in hospitalized children.^8,9 Postrenal causes are also called obstructive. Classic examples include posterior urethral valves and bladder catheter obstruction. It is also important to recognize that one type of injury can progress to another. For example, prerenal cases can progress to intrinsic if not addressed. Untreated hypoperfusion, for instance, may eventually result in intrinsic damage in the form of acute tubular necrosis.⁷ A patient with dehydration who is given ibuprofen may have components of both prerenal and intrinsic renal injury. Overall, the incidence of acute renal failure in children is increasing and many cases have multifactorial causes from different categories especially in hospitalized children.

HISTORY

The clinical presentation of acute renal failure varies depending on the underlying cause. The history and physical exam will provide clues to guide the workup. On history, urine changes should be assessed—color, volume, and frequency. Intake and output history will give information to assess volume status, and other elements of the history may provide clues to possible diagnosis. For example, history of bloody diarrhea will raise concern for hemolytic uremic syndrome. A thorough medication history is necessary and should include prescriptions, over-the-counter medications, supplements, and all other possible nephrotoxic substances. Systemic complaints such as fever, joint pain, and rash could indicate a postinfectious or rheumatologic condition. Edema raises suspicion for intrinsic renal disease.

PHYSICAL EXAM

Physical exam should focus on assessment of volume status. Careful attention should be given to heart rate, blood pressure (high or low), weight (change from “dry weight”), mucus membranes, and skin turgor. Assessment for areas of edema should be performed—lower extremity for ambulatory children, sacral for non-ambulatory and acutely ill children, and facial/peri-orbital in all. Growth parameter abnormalities can indicate the presentation of a chronic disease rather than an isolated acute process. The skin and musculoskeletal exam may provide clues to rheumatologic conditions. The abdominal exam may reveal enlarged bladder or palpable kidneys, a concerning sign for obstructive conditions.

The differential for acute renal failure is broad, and classically divided into prerenal, intrinsic, and postrenal categories (Table 110-2).