Acute Interstitial Nephritis Diagnosis and Management

Definition and Epidemiology

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines acknowledge that acute interstitial nephritis (AIN) accounts for 15-20% of all acute kidney injury cases, with the incidence of immune-related renal dysfunction being 2-7%, and the highest prevalence (5%) in patients receiving anti-PD(L)1/anti-CTLA-4 combination immunotherapy 1
The American Society of Nephrology notes that the median onset of immune-related AIN occurs at 3-4 months after initiating checkpoint inhibitor therapy, with AIN being diagnosed in 2.8% of all kidney biopsies and 13.5% of biopsies performed specifically for acute renal failure 1

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) recognizes that drug-induced AIN accounts for 60-70% of all cases, with medications triggering an antigen-initiated, cell-mediated immune response in the renal interstitium, and immune checkpoint inhibitors, such as anti-PD(L)1 and anti-CTLA-4 agents, being common culprits 1, 2
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) states that lymphocytic infiltrate with neutrophils and eosinophils in the interstitium is a characteristic finding in AIN, with progressive interstitial fibrosis if left untreated 1

The American College of Rheumatology notes that concomitant use of PPIs and NSAIDs during checkpoint inhibitor therapy significantly increases AIN risk, while pre-existing chronic kidney disease does not predispose to immune-related AIN 1
The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines state that most patients (majority) will have concurrent extra-renal immune-related adverse events 1

The European Society of Medical Oncology (ESMO) acknowledges that AIN typically presents with non-oliguric acute kidney injury characterized by modest but gradual increments in serum creatinine, often without classic symptoms, and that slowly progressive azotemia with creatinine elevation to 1.5-3× baseline or upper limit of normal is a key clinical feature 3
The American Society of Nephrology notes that oliguria, hematuria, peripheral edema, and anorexia may occur but are not universal, and that fever, rash, and eosinophilia are uncommon and should not be relied upon for diagnosis 4

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines state that renal biopsy remains the gold standard for definitive diagnosis of AIN, showing interstitial inflammation with lymphocytic infiltrate, tubulitis, and edema, and that mandatory initial exclusions include hypovolemia and dehydration, urinary tract obstruction, recent IV contrast exposure, urinary tract infection, medication-induced acute tubular necrosis, and hypotension or hypertensive emergency 1, 3, 6
The American College of Physicians notes that serum creatinine and BUN should be monitored, along with urinalysis with microscopy, and that urine protein-to-creatinine ratio (UPCR) or 24-hour protein collection should be performed if proteinuria is present 3, 4

The European Society of Medical Oncology (ESMO) recommends that for Grade 1 severity, checkpoint inhibitor therapy should be continued while monitoring, with no steroids required, and that for Grade 2 severity, checkpoint inhibitor therapy should be withheld, and oral prednisolone 0.5-1 mg/kg daily should be initiated after excluding other causes 3, 1
The American Society of Nephrology states that for Grade 3 severity, checkpoint inhibitor therapy should be withheld, and IV methylprednisolone 1-2 mg/kg daily should be initiated, with admission for inpatient monitoring and careful fluid balance 1, 3, 5, 6

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend using KDIGO criteria for AKI staging, which differs from CTCAE version 5.0 criteria, with Stage 1 (Grade 1) being creatinine 1.5-1.9× baseline or >0.3 mg/dL increase, Stage 2 (Grade 2) being creatinine 2.0-2.9× baseline, Stage 3 (Grade 3) being creatinine ≥3× baseline or ≥4.0 mg/dL or initiation of renal replacement therapy, and Grade 4 being creatinine >6× upper limit of normal 1, 3

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) notes that at 6 months post-diagnosis, 49% of patients with drug-induced AIN treated with steroids achieve complete recovery, 39% achieve partial recovery, and 12% have no recovery, with complete recovery being defined as creatinine within 25% of baseline or <1.4 mg/dL, partial recovery being ≥50% decrease from peak creatinine but not within 25% of baseline, and no recovery being <50% decrease from peak creatinine 7
The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines state that longer duration of drug exposure, delayed steroid initiation, delayed diagnosis and biopsy, and PPI-induced AIN are prognostic factors for poor recovery 1, 3, 5, 6