The Challenges of Acute Interstitial Nephritis: Time to Standardize.

Abstract

Acute interstitial nephritis (AIN) is a well-known cause of acute kidney disease (AKD) and CKD and is associated with progression to ESKD (1⇓⇓⇓⇓–6). Accordingly, it represents an important problem for clinicians caring for these patients. AIN is primarily an immune-mediated kidney injury triggered by use of certain medications, in particular antibiotics, PPIs, NSAIDs, and immune checkpoint inhibitors (ICPIs), or by autoimmune diseases, such as Sjogren syndrome, sarcoidosis, IgG4-related tubulointerstitial disease, and TINU. In developed countries, medications are the most common cause of AIN (>70%), whereas the number approximates 50% in developing countries. Infectious agents are a less common cause of AIN, except in developing countries. The overall incidence of AIN in kidney biopsy registries is 2%–5%, whereas AIN is observed in approximately 15%–20% of patients with AKI or AKD who undergo kidney biopsy (1⇓–3). The actual number is likely higher as many patients with AKI/AKD do not undergo biopsy and are presumed to have acute tubular injury (ATI). Importantly, diagnosing AIN clinically is often quite challenging, making kidney biopsy a frequent requirement to definitively confirm the diagnosis and guide therapy (Figure 1). Furthermore, delayed or missed AIN diagnosis leads to ongoing inflammation with resulting interstitial fibrosis, tubular atrophy, and permanent kidney damage, which may be the explanation for CKD occurring in 40%–60% of patients after an episode of AIN (4,5). Approximately 2% of CKD is considered to be due to AIN, which is equivalent to 10 million prevalent worldwide cases. Furthermore, AIN is the primary cause of ESKD in 3%–4% of incident patients (6). It is one of the few potentially treatable causes of AKI if identified and treated early. In view of these data, three key challenges that limit the diagnosis and management of patients suspected of having …