How do nonsteroidal anti inflammatory drugs cause acute kidney injury quizlet?
Published: 6 June 2013 Show PublicationsThis article is more than five years old. Some content may no longer be current. Prescriber Update 34(2):14–15 Key Messages
NSAIDs and Acute Kidney InjuryNSAIDs can cause two different forms of acute kidney injury1.
Acute kidney injury represents a continuum of renal injury ranging from clinically asymptomatic changes in renal function to renal failure and death. Acute kidney injury is characterised by a rapid fall in glomerular filtration rate (GFR) over hours to days. Presentation and DiagnosisThere are no specific signs or symptoms for NSAID induced acute kidney injury. Symptoms of acute kidney injury can be non-specific and may include shortness of breath, fatigue, confusion, nausea, decreased urine output and ankle/leg swelling2. Patients with pre-renal injury may have signs of volume depletion (eg, tachycardia, absolute or postural hypotension, low jugular venous pressure, dry mucous membranes). Patients with interstitial nephritis may have features of a systemic hypersensitivity including fever, arthralgia and a pruritic erythematous rash. Eosinophilia may also be present. Pathogenesis and Risk FactorsNSAIDs reversibly inhibit the production of renal prostaglandins via their inhibition of COX-1 and COX-2. Maximal inhibition occurs at steady state plasma concentrations (usually 3–7 days). Renal prostaglandins cause dilatation of the renal afferent arteriole. This mechanism is important for maintaining GFR when renal blood flow is reduced (ie, not in young, healthy people)1. Therefore, NSAID use is likely to have a greater effect on renal function in patients with other risk factors (Table 1). It is unclear how NSAIDs induce acute interstitial nephritis. However, it has been suggested that cyclooxygenase inhibition causes preferential conversion of arachidonic acid to leukotrienes, which may then activate helper T cells1. Table 1: Risk factors for NSAID induced acute kidney injury1, 2
ACE=Angiotensin Converting Enzyme; ARB=Angiotensin II Receptor Blocker Pre-existing chronic kidney disease and increasing age are the most common risk factors for developing acute kidney injury3. The 'Triple Whammy'A recent nested case-control study found that current use of triple therapy (ACE inhibitor/ ARB, diuretic and an NSAID) was associated with an increased rate of acute kidney injury (Rate Ratio 1.31, 95% CI 1.12–1.53) compared to double therapy (diuretic plus ACE inhibitor/ARB). The greatest risk was observed in the first 30 days of use (Rate Ratio 1.82, 95% CI 1.35-2.46)4. This ‘triple whammy’ effect was first identified from case reports in early 2000 and was highlighted in Prescriber Update in 20025. TreatmentRenal function will recover in most patients after withdrawal of NSAID therapy. Steroids may aid recovery in patients with interstitial nephritis who do not improve after stopping NSAID therapy. NSAID use should be avoided in the future in such patients1. New Zealand InformationNSAIDs are indicated to relieve moderate pain and inflammation associated with conditions such as rheumatic disorders, surgery and/or dysmenorrhoea. PHARMAC data indicates that ibuprofen is the most commonly prescribed NSAID in New Zealand. This is followed by diclofenac and naproxen. The Centre for Adverse Reactions Monitoring (CARM) received 119 reports of renal adverse reactions associated with NSAID (including COX-2 inhibitor) use from 1 January 2000 (Figure 1).
Figure 1: Renal adverse reaction reports from 1 January 2000 to 31 December 2012 Approximately 70% of reports were serious, including four deaths and 12 that were considered to be life-threatening. The majority of reports (74%) occurred in patients aged 50 years and over. Diclofenac was the most commonly implicated NSAID (53 reports). In two thirds of the reports, other medicines were also considered suspect, including four reports that described the ‘triple whammy’. Reports included acute renal failure (33 reports), renal tubular necrosis (5) and interstitial nephritis (12). Healthcare professionals are encourages to report suspected adverse reactions to NSAIDs to CARM. References
How do NSAIDs affect the kidneys?NSAIDs can induce several different forms of kidney injury including hemodynamically mediated acute kidney injury (AKI); electrolyte and acid-base disorders; acute interstitial nephritis (AIN), which may be accompanied by the nephrotic syndrome; and papillary necrosis (table 1).
How does diclofenac cause AKI?Objectives: Diclofenac induces oxidative stress in the body and became the main cause of nephrotoxicity and acute kidney injury (AKI). The traditional markers of AKI are blood urea and serum creatinine which are regarded as low sensitive and low specific in detection the early renal damage.
Which antiSome medications, such as ACE inhibitors, angiotensin II-receptor blockers and β-blockers, may increase NSAID-related renal complications. High acute dose of NSAIDs, have been implicated as causes of ARF, particularly in the elderly [193,194].
How do NSAIDs alter blood flow to the kidneys?NSAIDs may increase your fluid retention and can lead to decreased blood flow to kidneys. This is because NSAIDs block prostaglandins, which are the natural chemicals that dilate blood vessels and allow oxygen to reach the kidneys to keep them alive and healthy.
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