PMID- 33732993
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220421
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 6
IP  - 3
DP  - 2021 Mar
TI  - Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic 
      Syndrome.
PG  - 785-795
LID - 10.1016/j.ekir.2020.12.027 [doi]
AB  - INTRODUCTION: Glucocorticoids (GCs) are the primary treatment for nephrotic 
      syndrome (NS), although  approximately 10% to 20% of children develop steroid-resistant NS 
      (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at 
      initial disease presentation. We hypothesized that a plasma cytokine panel could 
      predict SRNS at disease presentation, and identify potential pathways regulating 
      SRNS pathogenesis. METHODS: Paired plasma samples were collected from 26 children 
      with steroid-sensitive NS (SSNS) and 14 with SRNS at NS presentation and after  approximately 7 
      weeks of GC therapy, when SSNS versus SRNS was clinically determined. Plasma 
      cytokine profiling was performed with a panel of 27 cytokines. RESULTS: We 
      identified 13 cytokines significantly different in Pretreatment SSNS versus SRNS 
      samples. Statistical modeling identified a cytokine panel (interleukin [IL]-7, 
      IL-9, monocyte chemoattractant protein-1 [MCP-1]) able to discriminate between 
      SSNS and SRNS at disease presentation (receiver operating characteristic [ROC] 
      value = 0.846; sensitivity = 0.643; specificity = 0.846). Furthermore, GC 
      treatment resulted in significant decreases in plasma interferon-gamma (IFN-gamma), tumor 
      necrosis factor-alpha (TNF-alpha), IL-7, IL-13, and IL-5 in both SSNS and SRNS patients. 
      CONCLUSIONS: These studies suggest that initial GC treatment of NS reduces the 
      plasma cytokines secreted by both CD4(+) T(H)1 cells and T(H)2 cells, as well as 
      CD8(+) T cells. Importantly, a panel of 3 cytokines (IL-7, IL-9, and MCP-1) was 
      able to predict SRNS prior to GC treatment at disease presentation. Although 
      these findings will benefit from validation in a larger cohort, the ability to 
      identify SRNS at disease presentation could greatly benefit patients by enabling 
      both avoidance of unnecessary GC-induced toxicity and earlier transition to more 
      effective alternative treatments.
CI  - (c) 2021 International Society of Nephrology. Published by Elsevier Inc.
FAU - Agrawal, Shipra
AU  - Agrawal S
AD  - Center for Clinical and Translational Research, The Research Institute at 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Pediatrics, College of Medicine, The Ohio State University, 
      Columbus, Ohio, USA.
FAU - Brier, Michael E
AU  - Brier ME
AD  - Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA.
AD  - Robley Rex Veterans Administration Medical Center, Louisville, Kentucky, USA.
FAU - Kerlin, Bryce A
AU  - Kerlin BA
AD  - Center for Clinical and Translational Research, The Research Institute at 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Pediatrics, College of Medicine, The Ohio State University, 
      Columbus, Ohio, USA.
FAU - Smoyer, William E
AU  - Smoyer WE
AD  - Center for Clinical and Translational Research, The Research Institute at 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Pediatrics, College of Medicine, The Ohio State University, 
      Columbus, Ohio, USA.
CN  - Pediatric Nephrology Research Consortium
LA  - eng
GR  - K08 DK103982/DK/NIDDK NIH HHS/United States
GR  - R01 DK095059/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20210106
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC7938200
OTO - NOTNLM
OT  - Steroids
OT  - biomarkers
OT  - cytokines
OT  - glucocorticoids
OT  - steroid-resistant nephrotic syndrome
OT  - steroid-sensitive nephrotic syndrome
FIR - Mahan, John
IR  - Mahan J
FIR - Patel, Hiren
IR  - Patel H
FIR - Ransom, Richard F
IR  - Ransom RF
FIR - Pan, Cynthia
IR  - Pan C
FIR - Geary, Denis F
IR  - Geary DF
FIR - Chang, Myra L
IR  - Chang ML
FIR - Gibson, Keisha L
IR  - Gibson KL
FIR - Iorember, Franca M
IR  - Iorember FM
FIR - Brophy, Patrick D
IR  - Brophy PD
FIR - Srivastava, Tarak
IR  - Srivastava T
FIR - Greenbaum, Larry A
IR  - Greenbaum LA
EDAT- 2021/03/19 06:00
MHDA- 2021/03/19 06:01
PMCR- 2021/01/06
CRDT- 2021/03/18 06:55
PHST- 2020/10/16 00:00 [received]
PHST- 2020/12/16 00:00 [revised]
PHST- 2020/12/22 00:00 [accepted]
PHST- 2021/03/18 06:55 [entrez]
PHST- 2021/03/19 06:00 [pubmed]
PHST- 2021/03/19 06:01 [medline]
PHST- 2021/01/06 00:00 [pmc-release]
AID - S2468-0249(20)31861-1 [pii]
AID - 10.1016/j.ekir.2020.12.027 [doi]
PST - epublish
SO  - Kidney Int Rep. 2021 Jan 6;6(3):785-795. doi: 10.1016/j.ekir.2020.12.027. 
      eCollection 2021 Mar.