Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis

Dennis G. Moledina, F. Perry Wilson, Jordan S. Pober, Mark A. Perazella, Nikhil Singh, Randy L. Luciano, Wassim Obeid, Haiqun Lin, Michael Kuperman, Gilbert W. Moeckel, Michael Kashgarian, Lloyd G. Cantley, Chirag Parikh

Research output: Contribution to journalReview article

Abstract

BACKGROUND. Clinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specifc T cell subsets such that specifc T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD). METHODS. We enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identifed 2 that were diagnostic of AIN. RESULTS. Of the 218 participants, 32 (15%) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-α and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-α levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]). CONCLUSIONS. Inclusion of urinary TNF-α and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.

Original languageEnglish (US)
Article numbere127456
JournalJCI Insight
Volume4
Issue number10
DOIs
StatePublished - May 16 2019

Fingerprint

Interleukin-9
Interstitial Nephritis
Urine
Kidney Diseases
Biomarkers
Acute Disease
Kidney
Biopsy
Cytokines
Diabetic Nephropathies
T-Lymphocyte Subsets
Proteinuria
Eosinophils
ROC Curve
Odds Ratio
T-Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Moledina, D. G., Perry Wilson, F., Pober, J. S., Perazella, M. A., Singh, N., Luciano, R. L., ... Parikh, C. (2019). Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. JCI Insight, 4(10), [e127456]. https://doi.org/10.1172/jci.insight.127456

Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. / Moledina, Dennis G.; Perry Wilson, F.; Pober, Jordan S.; Perazella, Mark A.; Singh, Nikhil; Luciano, Randy L.; Obeid, Wassim; Lin, Haiqun; Kuperman, Michael; Moeckel, Gilbert W.; Kashgarian, Michael; Cantley, Lloyd G.; Parikh, Chirag.

In: JCI Insight, Vol. 4, No. 10, e127456, 16.05.2019.

Research output: Contribution to journalReview article

Moledina, DG, Perry Wilson, F, Pober, JS, Perazella, MA, Singh, N, Luciano, RL, Obeid, W, Lin, H, Kuperman, M, Moeckel, GW, Kashgarian, M, Cantley, LG & Parikh, C 2019, 'Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis', JCI Insight, vol. 4, no. 10, e127456. https://doi.org/10.1172/jci.insight.127456
Moledina DG, Perry Wilson F, Pober JS, Perazella MA, Singh N, Luciano RL et al. Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. JCI Insight. 2019 May 16;4(10). e127456. https://doi.org/10.1172/jci.insight.127456
Moledina, Dennis G. ; Perry Wilson, F. ; Pober, Jordan S. ; Perazella, Mark A. ; Singh, Nikhil ; Luciano, Randy L. ; Obeid, Wassim ; Lin, Haiqun ; Kuperman, Michael ; Moeckel, Gilbert W. ; Kashgarian, Michael ; Cantley, Lloyd G. ; Parikh, Chirag. / Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. In: JCI Insight. 2019 ; Vol. 4, No. 10.
@article{a99513742eef4d79b24e3f079558aa18,
title = "Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis",
abstract = "BACKGROUND. Clinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specifc T cell subsets such that specifc T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD). METHODS. We enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identifed 2 that were diagnostic of AIN. RESULTS. Of the 218 participants, 32 (15{\%}) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-α and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-α levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]). CONCLUSIONS. Inclusion of urinary TNF-α and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.",
author = "Moledina, {Dennis G.} and {Perry Wilson}, F. and Pober, {Jordan S.} and Perazella, {Mark A.} and Nikhil Singh and Luciano, {Randy L.} and Wassim Obeid and Haiqun Lin and Michael Kuperman and Moeckel, {Gilbert W.} and Michael Kashgarian and Cantley, {Lloyd G.} and Chirag Parikh",
year = "2019",
month = "5",
day = "16",
doi = "10.1172/jci.insight.127456",
language = "English (US)",
volume = "4",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

TY - JOUR

T1 - Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis

AU - Moledina, Dennis G.

AU - Perry Wilson, F.

AU - Pober, Jordan S.

AU - Perazella, Mark A.

AU - Singh, Nikhil

AU - Luciano, Randy L.

AU - Obeid, Wassim

AU - Lin, Haiqun

AU - Kuperman, Michael

AU - Moeckel, Gilbert W.

AU - Kashgarian, Michael

AU - Cantley, Lloyd G.

AU - Parikh, Chirag

PY - 2019/5/16

Y1 - 2019/5/16

N2 - BACKGROUND. Clinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specifc T cell subsets such that specifc T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD). METHODS. We enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identifed 2 that were diagnostic of AIN. RESULTS. Of the 218 participants, 32 (15%) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-α and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-α levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]). CONCLUSIONS. Inclusion of urinary TNF-α and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.

AB - BACKGROUND. Clinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specifc T cell subsets such that specifc T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD). METHODS. We enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identifed 2 that were diagnostic of AIN. RESULTS. Of the 218 participants, 32 (15%) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-α and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-α levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]). CONCLUSIONS. Inclusion of urinary TNF-α and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.

UR - http://www.scopus.com/inward/record.url?scp=85070659600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070659600&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.127456

DO - 10.1172/jci.insight.127456

M3 - Review article

C2 - 31092735

AN - SCOPUS:85070659600

VL - 4

JO - JCI insight

JF - JCI insight

SN - 2379-3708

IS - 10

M1 - e127456

ER -