Acute Interstitial Nephritis: Maybe Nephrologists Don't Know It All

Tejas P. Desai, MD


February 06, 2020

Acute interstitial nephritis (AIN) has not garnered much attention from the nephrology world because we think we already know all about it. For decades the common teachings about AIN were that it was (a) caused by antibiotics, (b) easily diagnosed with a simple urine test, and (c) treated with antibiotic removal or occasionally with prednisone. Indeed, after nephrologists recognized which medications to avoid, the incidence of AIN dramatically decreased in the late 1980s (Figure 1).

Figure 1.

The incidence is creeping back up, however, and the first revelation is that it is proton pump inhibitors (PPIs) and immune checkpoint inhibitors (ICIs) that fuel the contemporary incidence of AIN, not antibiotics. Second, our reliance on urine tests, specifically the presence or absence of urine eosinophils, may have been misguided. With a sensitivity and specificity of 31% and 68%, respectively, eosinophiluria is a largely worthless diagnostic tool. Cases associated with PPIs and ICIs occur weeks or sometimes months after exposure, and patients rarely experience the triad of fever, rash, and eosinophilia. AIN isn't a benign condition, with some reports suggesting that it contributes to 10%-20% of acute kidney injury (AKI) cases.

Two studies have moved the needle on AIN prognostication.

Yale-AIN was a prospective study of 73 individuals with AKI who underwent kidney biopsy; those with biopsy-proven AIN (32 patients) had proteomic and metabolic testing. The investigators evaluated serum and urinary biomarkers and identified two potential diagnostic markers: urine TNF-alpha and urine IL-9. Analyzed together, the area under the curve to predict AIN was a healthy 0.83.

The Glasgow Renal Unit study analyzed tissue samples from patients with biopsy-proven AIN and categorized them into tertiles based on degree of tubular atrophy and nonfibrotic cortex inflammation. The patients were followed for 12 months to see if they recovered from AIN. As expected, the greater the amount of tubular atrophy, the less likely the patient recovered. Surprisingly, however, the more nonfibrotic cortex inflammation on biopsy, the greater the likelihood of recovery. Other researchers have seen this too.

It appears that AIN is a unique entity in which the presence of inflammation means less fibrosis and thus a better renal prognosis. The researchers propose a TANFI score ranging from 2 to 6; a score > 4 (based on the histopathology) predicts a slim chance of renal recovery.

AIN does not receive as many research dollars as any of the glomerulonephritides, but as these studies and others show, it is an important cause of AKI.

Dr Desai is a practicing nephrologist in Charlotte, North Carolina. His academic interests include the use of social media for physician, student, and patient education. He is the founder of NOD Analytics, a free social media analytics group that serves the medical education community. He has two wonderful children and enjoys spending time with them and his wife.

Follow Tejas P. Desai, MD, on Twitter: @nephondemand

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