Drug-induced or immune-mediated tubulointerstitial inflammation causing AKI.
Also known as: AIN, acute interstitial nephritis, drug-induced interstitial nephritis
Overview
An acute kidney injury characterized by inflammatory infiltrate of the renal interstitium with relative sparing of glomeruli and vessels. Most commonly drug-induced (>70%); also caused by infections, autoimmune disease, and idiopathic processes.
Epidemiology
Underdiagnosed cause of AKI; biopsy series suggest 5-15% of unexplained AKI is AIN. Incidence rising with proton pump inhibitor and checkpoint inhibitor use.
🔒 Free preview limit reached
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Acute Interstitial Nephritis (AIN) outline — plus all 514 diagnoses, 3,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Tubulointerstitial nephritis and uveitis (TINU) syndrome
Pathophysiology
Most drug-induced AIN is a delayed (type IV) hypersensitivity reaction independent of dose. Drug or drug-protein complexes act as haptens, triggering T-cell-mediated interstitial inflammation, eosinophil and lymphocyte infiltration, and tubular injury. Persistent inflammation leads to interstitial fibrosis if not addressed.
Clinical presentation
Symptoms
Often nonspecific: malaise, nausea, anorexia
Classic triad (fever, rash, eosinophilia) present in <10% — historically associated with methicillin
Flank pain in some cases
Many patients asymptomatic with AKI discovered on routine labs
Symptoms develop typically 1-3 weeks after starting offending drug (longer for NSAIDs and PPIs — months)
Signs / physical exam
Maculopapular rash (~15%)
Low-grade fever
Mild hypertension
Often unremarkable physical exam
Classic findings
Recent antibiotic exposure + AKI + sterile pyuria with eosinophils and WBC casts.
Differential diagnosis
Acute tubular necrosis — Recent ischemic or toxic insult; muddy brown casts; no eosinophils; no systemic hypersensitivity features
Prerenal AKI — Volume depletion; FENa <1%; bland sediment; responds to volume
Glomerulonephritis — Dysmorphic RBCs, RBC casts, heavy proteinuria, hypertension
Atheroembolic disease — Post-procedural; livedo reticularis, blue toes, eosinophilia
Diagnostic workup
Diagnostic criteria
Clinical diagnosis suggested by AKI + recent drug exposure + supportive sediment. Kidney biopsy is gold standard, showing interstitial inflammatory infiltrate (lymphocytes, eosinophils, plasma cells) with tubulitis. Biopsy recommended when diagnosis uncertain or no improvement after drug withdrawal.
Labs
BMP — AKI with elevated creatinine
Urinalysis with microscopy — sterile pyuria, WBC casts, eosinophiluria (Hansel or Wright stain — low sensitivity ~30%)
Mild proteinuria (subnephrotic, except NSAID-induced AIN which can cause nephrotic-range)
CBC with differential — peripheral eosinophilia (~30-50%, more common in antibiotic AIN)
Drug review with detailed exposure history including OTC and herbal
Imaging
Renal ultrasound — normal-sized kidneys, no obstruction; sometimes increased echogenicity
Gallium scan — historically used but rarely now (poor specificity)
Monitor creatinine — often improves within days to weeks after drug withdrawal
Treat any underlying infection
If multiple potential drugs, stop all non-essential agents
Second-line / adjunct
Glucocorticoids — prednisone 0.5-1 mg/kg/day for 4-6 weeks with taper — for biopsy-proven AIN with persistent AKI after drug withdrawal (typically started within 1-2 weeks)
Pulse methylprednisolone (250-500 mg × 3 days) for severe AKI requiring dialysis
Mycophenolate mofetil — second-line for steroid-refractory or steroid-dependent cases
Checkpoint inhibitor-induced AIN: hold ICI, give high-dose steroids, restart cautiously per oncology
Avoid re-exposure to the offending drug — note as allergy/adverse reaction
Complications
Incomplete recovery with residual CKD (40-60% have permanent reduction in GFR)
Progression to ESRD if delayed treatment or chronic NSAID/PPI exposure
Interstitial fibrosis from delayed diagnosis
Steroid-related complications
Re-exposure can cause rapid recurrence
PANCE pearls
Classic triad of fever, rash, eosinophilia is present in <10% of patients — its absence does NOT exclude AIN.
PPIs and NSAIDs cause AIN over weeks to months (vs antibiotics over 1-3 weeks). Always review the full medication list.
Eosinophiluria has low sensitivity (~30%) and specificity (also positive in atheroemboli, UTI, prostatitis). Negative test does not exclude AIN.
Biopsy is recommended if creatinine does not improve within 1-2 weeks of stopping the suspected drug, before committing to steroids.
NSAID-induced AIN can present with nephrotic-range proteinuria (concurrent minimal change-like glomerular involvement).
References
KDIGO 2012 — KDIGO Clinical Practice Guideline for Acute Kidney Injury
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.