Non-steroidal Anti-inflammatory Drugs: Clinical Implications, Renal Impairment Risks, and AKI

Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.

Acute kidney injury is a heterogeneous group of conditions characterized by a sudden decrease in glomerular filtration rate, manifested by an increase in serum creatinine concentration or oliguria, and classified by stage and cause. This type of injury occurs in approximately 20% of hospitalized patients, with major complications including volume overload, electrolyte disorders, uremic complications, and drug toxicity. Management includes specific treatments according to the underlying cause and supportive treatment to prevent and manage complications. Kidney replacement therapy is used when complications cannot be managed with medical therapy alone. Despite advances in care, the mortality rate in patients requiring kidney replacement therapy remains approximately 50%.

The association between acute kidney injury (AKI) and use of non-steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little is known about the comparative risk of individual NSAIDs, including specific COX-2 inhibitors.