ESSENTIALS OF DIAGNOSIS
Nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI) develops predominantly in patients with underlying risk factors.
Clinical presentations can be asymptomatic or associated with uremic symptoms, edema (pulmonary and peripheral), hypertension, or electrolyte and acid–base disturbances.
Elevated blood urea nitrogen (BUN) and serum creatinine (Cr) concentrations are present.
An elevated BUN/Cr ratio (>20) is often noted.
Hyponatremia (serum [Na+] <135 mEq/L), hyperkalemia (serum [K+] >5.5 mEq/L), and nonanion gap metabolic acidosis (serum [HCO3–] <20 mEq/L) are common.
Urine [Na+] <10–20 mEq/L and FENa+ <1.0% characterize NSAID-associated AKI.
AKI is generally reversible with discontinuation of NSAIDs and treatment of concurrent disease processes.
Severe AKI from NSAIDs may require dialysis.
A. Epidemiology of Nonsteroidal Anti-inflammatory Drug Use
NSAIDs are employed widely to treat pain, fever, and inflammation. Other potential uses for these drugs include treatment and prevention of colonic polyposis and Alzheimer-type dementia. The first NSAID discovered was sodium salicylate in 1763. In 1950, phenylbutazone was introduced into clinical practice. It was efficacious, but its use faded due to bone marrow toxicity. Subsequently, indomethacin entered the market in the 1960s. More than 20 NSAIDs from seven major classes, including the selective cyclooxygenase (COX)-2 inhibitors (Table 15–1), are available in the United States. In addition to prescription NSAIDs, a large percentage of the general population consumes over-the-counter NSAIDs. Annually, more than 50 million patients ingest these drugs on an intermittent basis, while some 15–25 million people in the United States use an NSAID on a regular basis. Importantly, the elderly patients who are at risk for multiple complications of NSAID therapy constitute a growing population that has a prevalence of NSAID use as high as 15–20%.
Table 15–1.Classes of nonsteroidal anti-inflammatory drugs. ||Download (.pdf) Table 15–1. Classes of nonsteroidal anti-inflammatory drugs.
|Class ||Trade Name ||Total Dose/Day (Dosing Interval) |
|Carboxylic acids |
|Aspirin ||Aspirin ||2.4–6.0 g (qid) |
|Salsalate ||Disalcid ||1.5–3.0 g (bid) |
|Choline magnesium ||Trilisate ||1.5–3.0 g (bid–tid) |
|Diflunisal ||Dolobid ||0.5–1.5 g (bid) |
|Acetic acids |
|Indomethacin ||Indocin ||75–150 mg (bid–qid) |
|Tolmetin ||Tolectin ||400–2400 mg (bid–tid) |
|Sulindac ||Clinoril ||200–400 mg (bid) |
|Diclofenac || |
100–150 mg (bid)
100 mg (bid)
|Etodolac ||Lodine ||400–1200 mg (bid–qid) |
|Ketorolac ||Toradol || |
Oral 40 mg (qid)
Intravenous 60–120 mg (qid)
|Propionic acids |
|Ibuprofen ||Motrin, Rufen ||800–3200 mg (qid) |
|Naproxen || |
500–1000 mg (bid)
450 mg (bid)
|Ketoprofen ||Orudis ||225 mg (tid) |
|Flurbiprofen ||Ansaid ||200–300 mg (bid–tid) |
|Fenoprofen ||Nalfon ||1200–2400 mg (qid) |
|Oxaprozin ||Daypro ||1200 mg (qd) |
|Enolic acids |
|Piroxicam ||Feldene ||10–20 mg (qd) |
|Phenylbutazone ||Butazolidin ||300–600 mg (tid) |
|Mefenamic acid ||Ponstel ||1000 mg (qid) |
|Meclofenamate ||Meclomen ||150–400 mg (tid–qid) |
|Nabumetone ||Relafen ||1000–1500 mg (bid–tid) |
|COX-2 inhibitors |
|Celecoxib ||Celebrex ||100–400 mg (qd–bid) |
B. Epidemiology of Nonsteroidal Anti-inflammatory Drug-Associated Acute Kidney Injury