Urinary cytokine levels may be effective diagnostic biomarkers for acute interstitial nephritis
Researchers found patients who were diagnosed with acute interstitial nephritis had higher levels of urinary TNF-alpha and interleukin-9, which suggests that testing these levels could improve clinical diagnosis, according to a published study.
“Unlike many other causes of acute loss of kidney function, acute interstitial nephritis is treatable,” Dennis G. Moledina, MD, of the Yale School of Medicine, and colleagues wrote in their study. “However, ongoing inflammation can lead to permanent kidney damage in acute interstitial nephritis if it is not diagnosed and treated promptly. Thus, a noninvasive biomarker for timely diagnosis could improve clinical care of patients suspected to have acute interstitial nephritis and may reduce occurrence of chronic kidney disease. A major challenge of acute interstitial nephritis is distinguishing it from other causes of acute rise in serum creatinine.”
To determine if specific cytokine patterns were higher in patients with acute interstitial nephritis, researchers prospectively enrolled 218 patients who underwent a kidney biopsy for acute kidney disease evaluation between 2015 and 2018. Diagnosis of acute interstitial nephritis was independently established through the evaluation of biopsy slides by three renal pathologists who were blinded to patients’ clinical history and official biopsy report (79 cases of acute interstitial nephritis with official biopsy report; 28 without the condition). Researchers then measured biomarkers from plasma and urine samples, conducting univariable and multivariable analysis of 12 cytokines.
Of the 12 selected urine and plasma cytokines, researchers identified two that were diagnostic of acute interstitial nephritis (TNF-alpha and IL-9). Patients with acute interstitial nephritis had higher levels of urine TNF-alpha and IL-9 than those without any kidney disease or with other diagnoses (acute tubular injury, glomerular diseases and diabetic kidney disease, for example).
In addition, after controlling for blood eosinophils, leukocyturia and proteinuria, researchers observed higher odds of acute interstitial nephritis in patients in the highest quartiles of TNF-alpha levels (adjusted OR = 10.9) and IL-9 levels (aOR = 7.5).
“Urine TNF-[alpha] and IL-9 are consistently associated with acute interstitial nephritis and improve discrimination over a clinician’s prebiopsy diagnosis and a model of currently available clinical tests,” the researchers wrote. “These results could guide diagnostic approaches in patients suspected to have acute interstitial nephritis for early management that could supplement or replace a kidney biopsy. Moreover, our findings point to potentially novel insights into the role of mast cells and Th9 cells in acute interstitial nephritis for future mechanistic studies.” – by Melissa J. Webb
Disclosure: Moledina reports being a named inventor on a provisional patent entitled, “System and methods for diagnosing acute interstitial nephritis.”