Pathophysiology
Summary
Acute interstitial nephritis (AIN) is a form of intrinsic acute kidney injury (AKI), and manifests in both acute and chronic forms. AIN is precipitated by drugs such as NSAIDs, furosemide, penicillin, and sulfonamides. It can be mediated through either type I hypersensitivity or type IV hypersensitivity reactions, resulting in the release of proinflammatory substances that damage the renal tubules and interstitium, leading to interstitial edema and a diffuse inflammatory infiltrate on histology. Clinical features of AIN include fever, rash, and oliguria, as well as increased BUN & creatinine. AIN symptoms usually manifest 1-2 weeks post-exposure.
Chronic interstitial nephritis is associated with prolonged exposure to certain substances and autoimmune disorders like Sjögren syndrome and lupus. Analgesic nephropathy is associated with chronic NSAID use, which can accumulate in the renal papillae, resulting free radical damage and patchy inflammation. Over time, this leads to interstitial fibrosis and microvascular damage, eventually resulting in renal papillary necrosis and chronic kidney disease (CKD).
Lesson Outline
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FAQs
Tubulointerstitial nephritis, including its acute form known as acute interstitial nephritis (AIN), is characterized by inflammation of the renal interstitium. Symptoms of AIN usually appear 1-2 weeks after exposure to the insulting agent and often presents with a fever and rash, as well as oliguria, eosinophilia and eosinophiluria, and WBC casts. AIN causes intrinsic acute kidney injury (AKI), marked by various metabolic and hemodynamic abnormalities, including increased serum BUN and increased creatinine. Chronic forms of this condition often lead to chronic kidney disease, manifesting as bilaterally small, scarred kidneys.
NSAIDs, furosemide, penicillin, and sulfonamide drugs such as TMP/SMX are associated with acute interstitial nephritis. These drugs can cause AIN through either type I hypersensitivity reactions, involving IgE cross-linking on mast cells, or type IV delayed-type hypersensitivity reactions, where APCs activate Th1 helper T-cells, resulting in inflammatory damage.
NSAIDs can precipitate both acute and chronic interstitial nephritis (AIN), With chronic use, they can also cause analgesic nephropathy, a form of chronic tubulointerstitial nephritis. NSAIDs accumulate at the renal papillae and cause free radical damage, leading to patchy inflammation and calcification. Over time, this chronic inflammation results in interstitial fibrosis, microvascular damage, and vasoconstriction of afferent renal vessels, culminating in ischemia and renal papillary necrosis.
In acute interstitial nephritis (AIN), histology typically shows interstitial edema accompanied by a diffuse inflammatory infiltrate. In chronic conditions like analgesic nephropathy, interstitial fibrosis is commonly observed.
Chronic NSAID use, often seen in patients with chronic pain conditions like back pain and migraines, can lead to analgesic nephropathy, a form of chronic tubulointerstitial nephritis. Other risk factors include chronic exposure to lead and lithium. Autoimmune diseases such as Sjögren syndrome and lupus are also associated with chronic forms of this condition.
