What is the diagnosis of Acute Interstitial Nephritis (AIN)?

From the Guidelines

Diagnosis of acute interstitial nephritis (AIN) should be approached with a comprehensive evaluation including clinical assessment, laboratory tests, and consideration of kidney biopsy, as recommended by the most recent guidelines 1.

Key Diagnostic Steps

• Evaluate for classic symptoms including fever, rash, eosinophilia, and acute kidney injury, though these may not always be present.
• Laboratory tests should include urinalysis (looking for pyuria, hematuria, white cell casts, and sometimes eosinophiluria), complete blood count (checking for eosinophilia), and kidney function tests (elevated creatinine and BUN) 1.
• Imaging studies like ultrasound may show enlarged kidneys but are primarily used to rule out other causes of kidney injury.
• The timing of kidney injury in relation to medication exposure is crucial, as drug-induced AIN typically occurs 7-10 days after starting a new medication (or sooner with re-exposure).

Importance of Biopsy

• Kidney biopsy is the most definitive diagnostic method, revealing characteristic findings of interstitial inflammation, tubulitis, and edema 1.
• Early consideration for renal biopsy is helpful and may negate the need for steroids, determining whether renal deterioration is related to immune-related adverse events or other pathology 1.

Management and Outcome

• Prompt diagnosis is essential as early intervention, particularly discontinuation of the offending agent, significantly improves outcomes and prevents progression to chronic kidney disease.
• Management should follow guidelines for the treatment of immune-related adverse events, including the use of steroids and the consideration of renal replacement therapy in severe cases 1.

From the Research

Diagnosis of Acute Interstitial Nephritis (AIN)

• AIN is an under-recognized and under-diagnosed cause of acute kidney injury (AKI), accounting for 15-20% of cases of AKI 2, 3.
• The key to early diagnosis is vigilance for the presence of tubular dysfunction in non-oliguric individuals, especially in patients with modest but gradual increments in creatinine level 2.
• Diagnosis of AIN can be challenging, especially when multiple causes are suspected to be present simultaneously, such as infection and antibiotic-induced AIN 4.
• Renal biopsy is the gold standard for diagnosing AIN, but it may not be able to pinpoint the precise cause of AIN 4.

Clinical Features and Biomarkers

• Clinical features of AIN include oliguria, arthralgia, fever, rash, and loin pain 5.
• Biomarkers such as serum and urine cytokines and chemokines, cellular biomarkers, and genetic biomarkers may be useful in diagnosing AIN, but more research is needed to determine their utility 4.
• Urinary biomarkers may be useful in diagnosing AIN in its early stages, but their utility remains to be determined 2.

Treatment and Outcomes

• Prompt recognition, elimination of the offending source of antigen, and use of a limited course of steroid therapy where indicated, can result in complete resolution in ~65% of cases, partial resolution in up to 20%, and irreversible damage in the rest 2.
• Steroid therapy may improve the recovery of renal function, especially when administered early (within 7 days after diagnosis) 3.
• However, the use of steroid therapy in AIN is still a topic of debate, and some studies have found no significant difference in outcome between patients who received corticosteroid therapy and those who did not 5, 6.
• Moderate to severe interstitial fibrosis and tubular atrophy (IFTA) and dialysis requirement are significant predictors of decreased kidney recovery in AIN 6.