AIN and ATN

Question 1

Acute interstitial nephritis (AIN)

Answer 1

• AIN is an autoimmune inflammatory reaction characterized by interstitial edema and infiltration of inflammatory cells (T cells, plasma cells, eos)
• Manifestations range from ASx to AKI, most common features seen are fever, rash, arthralgias, eosinophils in urine
• The “classic triad” is fever, rash, urine eos
• This is a hypersensitivity reaction (usually to penicillins/cephalosporins/sulfonamides/NSAIDs), but it leaves the glomeruli and renal vasculature normal
• Signs of AIN include oliguria
• Una >20 and FeNa >2% (renal cause; can’t reabsorb Na)
• Urinalysis: RBCs, WBCs, WBC casts, urine eos, some protein

Question 2

NSAID nephrotoxicity

Answer 2

• Can cause a variety of AKIs, including AIN (w/ or w/o nephrotic syndrome)
• AKI due to NSAIDs blocking COX and leading to a decease in PGE causing vasoconstriction
• While this can cause an AIN, it is not the same as typical hypersensitivity AIN (not the same Sx/signs)
• These pts may have nephrotic syndrome most likely due to minimal change from T cell dysfxn
• Most forms of drug-induced AIN are self-limiting once the offending drug is discontinued

Question 3

ATN

Answer 3

• Caused by many things, mostly aminoglycosides (gentamycin), IV contrast, ampotericin
• Characterized by tubular epithelial cell necrosis showing RBC, muddy brown granular casts and tubular epithelial cell casts in urine sed
• Pts present w/ uremic Sx: weakness/fatigue, nausea/vomiting, metabolic acidosis, mental changes

Question 4

Aminoglycoside nephrotoxicity

Answer 4

• One of the most common forms of ATN, usually occurs 7-10 days after Rx and produces AKI w/ normal urine output
• Rx is supportive w/ discontinuation of the aminoglycoside
• Prophylaxis: adequate fluids, avoid simultaneous use of other nephrotoxins, use lowest dose, monitor, adjust according to renal function

Question 5

Radiocontrast ATN

Answer 5

• In part tubular injury is due to fee radical generation and fall in renal perfusion (due to endothelia release)
• Incidence is negligible in pts w/ normal renal function but increases for those w/ impaired renal function
• Risk factors: old age, renal problems, DM, CHF, cirrhosis, high dose
• ATN will usually appear 24-48 hrs after the administration of contrast (normal urine output)
• Recovery is one week
• Prevention: .9% NS will expand plasma volume to prevent this

Question 6

Amphotericin ATN and Nephrogenic systemic fibrosis

Answer 6

• In amphotericin ATN there is a dose-dependent decline in GFR w/ oliguria or anuria
• Can lead to hypokalemia and hypomagnesemia
• Can be prevented by NS
• Nephrogenic systemic fibrosis (NSF): pts develop large areas of hardened skin w/ fibrotic nodules and plaques
• NSF due to someone w/ renal failure is given gadolinium contrast
• Analgesic abuse nephritis (AAN): main culprit is phenacetin (maybe aspirin, acetaminophen) and causes a chronic interstitial nephritis due to decreased renal bloodflow

Question 7

Pre renal AKI

Answer 7

• Decreased RBF leads to: decreased GFR, azotemia (elevated Cr, BUN), and oliguria (typical AKI findings)
• There’s reabsorption of fluid (RAAS active) since there is decreased kidney blood flow
• BUN will always follow the direction of bulk flow, thus BUN reabsorption is also increased
• This leads to a serum BUN:Cr >15 (normal is 15)
• Since tubular function is intact the FeNa will be low (500)

Question 8

Post renal AKI

Answer 8

• Due to obstruction after kidneys, leads to back pressure which reduces GFR and causes other AKI findings
• Early stages: like pre-renal AKI, there is overall reabsorption of water and thus BUN in tubules (tubules are intact)
• Therefore in early stages the FeNa will be 500 and BUN:Cr >15
• Late stages: like ATN, there is eventually damage to the renal tubule epithelia and therefore decreased reabsorption of H2O, BUN, Na
• Leads to inability to concentrate urine (Uosm 2% and BUN:Cr <15

Question 9

Overview of ATN

Answer 9

• Due to LOF of tubule epithelial cells, there is BUN:Cr 2%, and Uosm <500
• Elevated BUN and Cr
• Hyperkalemia (decreased K secretion) w/ anion gap metabolic acidosis (decreased H+ secretion)
• Ischemic ATN is often preceded by pre renal AKI
• Toxic ATN: aminoglycosides, heavy metals, myoglobinuria, ethylene glycol (also forms CaOx crystals), radiocontrast, urate (tumor lysis syndrome)

Question 10

Overview of AIN

Answer 10

• Inflammation of just the interstitium
• Often caused by NSAIDs, penicillins, diuretics
• Presentation: oliguria w/ fever and rash
• Eos in urine
• Resolves w/ cessation of drug
• May progress to renal papillary necrosis
• Renal papillary necrosis: presents w/ gross hematuria and flank pain
• Causes of RPN: NSAID abuse (phenacetin, aspirin), DM, SCD, severe acute pyelonephritis