Kidney Week

Abstract: FR-PO001

T Cell-Derived Cytokines in Urine as Biomarkers for Clinical Diagnosis of Acute Interstitial Nephritis

Session Information

• AKI: Clinical, Outcomes, Trials - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Moledina, Dennis G., Yale School of Medicine, New Haven, Connecticut, United States

Dennis G. Moledina,

• Luciano, Randy L., Yale School of Medicine, New Haven, Connecticut, United States

Randy L. Luciano,

• Wilson, Francis Perry, Yale School of Medicine, New Haven, Connecticut, United States

Francis Perry Wilson,

• Obeid, Wassim, Yale School of Medicine, New Haven, Connecticut, United States

Wassim Obeid,

• Kuperman, Michael Benjamin, Arkana Laboratories, Little Rock, Arkansas, United States

Michael Benjamin Kuperman,

• Moeckel, Gilbert W., Yale School of Medicine, New Haven, Connecticut, United States

Gilbert W. Moeckel,

• Kashgarian, Michael, Yale School of Medicine, New Haven, Connecticut, United States

Michael Kashgarian,

• Pober, Jordan S., Yale School of Medicine, New Haven, Connecticut, United States

Jordan S. Pober,

• Perazella, Mark A., Yale School of Medicine, New Haven, Connecticut, United States

Mark A. Perazella,

• Cantley, Lloyd G., Yale School of Medicine, New Haven, Connecticut, United States

Lloyd G. Cantley,

• Parikh, Chirag R., Yale School of Medicine, New Haven, Connecticut, United States

Chirag R. Parikh,

Background

The current clinical diagnosis of acute interstitial nephritis (AIN) is challenging as it relies on combining a high-index of clinical suspicion with subsequent biopsy confirmation. We hypothesized that AIN is a T cell-mediated process and tested urine for cytokines associated with T cell immunity as biomarkers for clinical diagnosis of AIN

Methods

We enrolled consecutive participants who underwent a kidney biopsy for evaluation of acute kidney disease at 2 academic hospitals from 2015 to 2017. We measured 6 cytokines associated with T cell-mediated inflammation (TNFα, IFNγ, IL2, IL4, IL5, and IL13) in urine samples collected before the biopsy. We established AIN diagnosis through adjudication of histological images by 3 independent renal pathologists. We considered univariable and multivariable associations of clinical variables and biomarkers with AIN to develop a clinical diagnostic model

Results

Of the 154 participants, 35 (23%) had AIN and 119 had other diagnoses including acute tubular injury (n=37), diabetic kidney disease (n=15), arterionephrosclerosis (n=18), glomerular disease (n=40), and others (n=9). Patients with AIN had higher levels of TNFα and IL2 (Figure). The AUC for AIN diagnosis based on clinicians’ pre-biopsy diagnosis was 0.59 (0.50-0.69). The AUC of a model containing urinary markers of inflammation (pyuria) and glomerular injury (hematuria and proteinuria) was 0.72 (0.62-0.81), which increased on addition of TNFα and IL2 to 0.82 (0.73-0.90; P<0.001) and 0.76 (0.67-0.85; P=0.009), respectively

Conclusion

Urine cytokines associated with T cell immunity were higher in patients with AIN as compared with those who had other diagnoses. These biomarkers significantly improved discrimination for AIN compared to clinicians’ prebiopsy suspicion of AIN

Funding

• NIDDK Support