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NORMAL RENAL FUNCTION AND THE DEFINITON OF AKI

The kidneys are responsible for many physiologic functions imperative to homeostasis, including:

  • Excretion of organic anions, water-soluble metabolites and drugs

  • Regulation of acid–base balance

  • Regulation of sodium, chloride, and potassium serum levels

  • Regulation of serum osmolality and free water balance

  • Production of erythropoietin

  • Vitamin D metabolism

  • Regulation of systemic vascular resistance through production of renin and angiotensin

The kidneys also receive up to 20% of the cardiac output, making them very sensitive to changes in blood pressure, oxygen delivery, and/or cardiac output.

Acute kidney injury (AKI) is a broad clinical term that includes the subtle signs of renal impairment such as edema or acidosis and extends to complete renal failure and anuria. Staged definitions have been developed to accommodate for the wide clinical variability of patients with a diagnosis of AKI.

CAUSES OF PEDIATRIC AKI

Classically the causes of AKI have been categorized as pre-renal, intrinsic, and post-renal. However, the causes of AKI in critically ill children are more complex and multifactorial than these categories suggest.

Common causes of AKI in the PICU include:

  • Hypoxic-ischemic injury

  • Sepsis, cytokine, or toxin mediated

  • Multiorgan dysfunction syndrome

  • Nephrotoxic medications

    • Causes 25% of pediatric AKI: aminoglycosides, NSAIDs, radiopaque contrast, immunosuppressive therapy

  • Oxidative stress and hypoxia

  • Intravascular volume depletion

  • Glomerulonephritis

  • Interstitial nephritis: idiopathic or drug induced

  • Tumor lysis syndrome

  • Rhabdomyolysis

  • Acute tubular necrosis

  • Renal vascular thrombus

  • Hemolytic uremic syndrome

  • Obstruction of urinary flow from posterior urethral valves, nephrolithiasis, trauma

Children with critical illness are especially vulnerable to AKI as intrinsic renal function does not approach adult levels until over 1 year of age. Neonates and premature infants in normal health have an estimated glomerular filtration rate (GFR) of 50 to 60 mL/min/1.73 m2 whereas a healthy adult GFR is approximately120 mL/min/1.73 m2.1

DIAGNOSING PEDIATRIC AKI

Approximately 10% of critically ill children will have AKI, most often around the third hospital day.2 The presence of any signs of renal dysfunction, including fluid overload, systemic hypertension (blood pressure >95th percentile for age and sex), and/or electrolyte derangement should prompt investigation for AKI. The clinical correlate to describe renal function is the GFR, expressed in mL/min/1.73 m2.

SERUM CREATININE AS A MEASURE OF GFR

The most available serum biomarker of renal function is serum creatinine (SCr). There is a simple bedside calculation to convert SCr levels to an estimated GFR3:

eGFR=41.3×(Height(m)SCr)

This equation often overestimates renal function, especially in extremes of age and renal function.

As a by-product of muscle mass with dynamic changes in excretion and renal tubule absorption, SCr has multiple disadvantages as an indicator of renal function in children with critical illness.

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