Drug‐induced acute kidney injury in children

Abstract

Acute kidney injury (AKI) is a serious problem occurring in anywhere between 8 and 30% of children in the intensive care unit. Up to 25% of these cases are believed to be the result of pharmacotherapy. In this review we have focused on several relevant drugs and/or drug classes, which are known to cause AKI in children, including cancer chemotherapeutics, non-steroidal anti-inflammatory drugs and antimicrobials. AKI demonstrates a steady association with increased long term risk of poor outcomes including chronic kidney disease and death as determined by the extent of injury. For this reason it is important to understand the causality and implications of these drugs and drug classes. Children occupy a unique patient population, advocating the importance of understanding how they are affected dissimilarly compared with adults. While the kidney itself is likely more susceptible to injury than other organs, the inherent toxicity of these drugs also plays a major role in the resulting AKI. Mechanisms involved in the toxicity of these drugs include oxidative damage, hypersensitivity reactions, altered haemodynamics and tubule obstruction and may affect the glomerulus and/or the tubules. Understanding these mechanisms is critical in determining the most effective strategies for treatment and/or prevention, whether these strategies are less toxic versions of the same drugs or add-on agents to mitigate the toxic effect of the existing therapy.

A child with acute kidney injury

“…In aminoglycosides, nephrotoxicity is associated with a varying degree of renal tubular dysfunction that may, in the most severely affected patients, lead to AKI. Aminoglycosides cause damage primarily to tubular epithelial cells 3 (particularly proximal tubular cells 5 ), but can also have an adverse effect on renal function via activation of the renin-angiotensin-aldosterone system and changes of glomerular endothelial cells. 3 Other mechanisms involved are the direct and indirect effects on the mitochondria that lead to the disruption of electron transport and ATP production and the production of reactive oxygen species.…”

“…Most patients recover but some can progress to chronic interstitial nephritis. 5 There are several risk factors that can increase the nephrotoxic potential of aminoglycosides, such as preexisting renal disease, treatment for more than 10 days, higher trough levels and hypoalbuminemia. 4 The role of vancomycin as a nephrotoxin remains controversial, particularly in the context of monotherapy with appropriate drug monitoring levels.…”

“…4 The role of vancomycin as a nephrotoxin remains controversial, particularly in the context of monotherapy with appropriate drug monitoring levels. 5 However, there is evidence that vancomycin has detrimental oxidative effects on proximal tubule cells. 3 The exact mechanism of nephrotoxicity remains unclear, but may be related to oxidative effects on the proximal tubule.…”

The multifaceted role of the renal microvasculature during acute kidney injury

“…AKI is one of the most serious and common health complications, occurring in up to 20 % of all hospitalized patients and over 45 % of patients in critical care settings [2, 3]. While not well defined in children, the incidence of AKI in pediatric intensive care units is reported to range from 8 to 30 % and occurs in roughly 7 % of the general pediatric population [4–6]. The incidence of AKI in children appears to be increasing, and the etiology over the past decades has shifted from primary renal disease to multi-factorial causes, particularly in hospitalized children.…”

“…An important cause of AKI in hospitalized children is the setting of post-cardiac surgery and stem cell transplantation [7]. Pharmacotherapy is also one of the major causes of AKI and may play a causative role in as many as 25 % of all pediatric cases [6, 8]. Drugs, including antimicrobials, chemotherapeutic agents, and non-steroidal anti-inflammatory drugs, among others, have all been implicated in drug-induced renal injury in children [5].…”