Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment

Background: Acute tubulointerstitial nephritis (ATIN) diagnosis lays on histological assessment through a kidney biopsy, given the absence of accurate non-invasive biomarkers. The aim of this study was to evaluate the accuracy of different urinary inflammation-related cytokines for the diagnostic of ATIN and its distinction from acute tubular necrosis (ATN). Methods: We included 33 patients (ATIN (n = 21), ATN (n = 12)), and 6 healthy controls (HC). We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay at the time of biopsy and after therapy, and registered main clinical, analytical and histological data. Results: At the time of biopsy, urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were significantly higher in ATIN compared to HC. A positive correlation between the extent of the tubulointerstitial cellular infiltrates in kidney biopsies and the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF was observed. Notably, I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN than in ATN, with I-TAC/CXCL11 as the best discriminative classifier AUC (0.77, 95% CI 0.57–0.95, p = 0.02). A combinatory model of these three urinary cytokines increased the accuracy in the distinction of ATIN/ATN compared to the individual biomarkers. The best model resulted when combining the three cytokines with blood eosinophil and urinary leukocyte counts (LR = 9.76). Follow-up samples from 11ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Conclusions: Urinary I-TAC/CXCL11, CXCL10, IL6 and MCP-1 levels accurately distinguish patients developing ATIN from ATN and healthy individuals and may serve as novel non-invasive biomarkers in this disease.

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MO335URINARY CYTOKINES REFLECT THE ONGOING RENAL INFLAMMATION IN THE DIAGNOSTIC OF ACUTE TUBULOINTERSTITIAL NEPHRITIS: RESULTS OF A MULTIPLEX BEAD-BASED ASSAY ASSESSMENT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab084.008 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Laura Martinez Valenzuela ◽

Juliana Draibe ◽

Xavier Fulladosa ◽

Francisco Gomez Preciado ◽

Ernest Nadal ◽

...

Keyword(s):

Tubulointerstitial Nephritis ◽

Urinary Concentration ◽

Blood Eosinophil ◽

Healthy Controls ◽

Acute Tubulointerstitial Nephritis ◽

Positive Correlation ◽

Luminex Assay ◽

Urinary Levels ◽

Multiplex Bead

Abstract Background and Aims Acute tubulointerstitial nephritis (ATIN) diagnostic lays on the kidney biopsy given the absence of non-invasive biomarkers for disease demonstration and follow-up. The aim of this study was to evaluate the accuracy of ten urinary inflammatory-related cytokines in the diagnostic of ATIN and its clinical distinction from acute tubular necrosis (ATN). Method Observational prospective study including 21 ATIN and 12 ATN patients, and 6 healthy controls. We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay. We registered clinical, analytical and histological data from the medical records. Results Urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were higher in ATIN compared to healthy controls. In contrast, healthy controls exhibited higher EGF urinary levels compared to ATIN patients. Follow-up samples available from 11/21 ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Urinary levels of I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN compared to ATN patients, with I-TAC/CXCL11 as the best discriminatory biomarker based on its higher AUC in the ROC curve and likelihood ratio. The combinatory model of the three cytokines increased the sensitivity of the individual biomarkers in the distinction of ATIN/ATN but the best results were obtained when blood eosinophil count and leukocyturia were added to the model. We found a positive correlation of the extent of the tubulointerstitial infiltrate in kidney biopsies with the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF, indicating the potential renal source of the cytokines Conclusion the higher cytokine levels in ATIN compared to ATN patients and healthy controls, the significant decline after treatment and the positive correlation of the cytokines with the grade of the inflammatory infiltrate allows us to propose I-TAC/CXCL11, CXCL10, IL6 and MCP-1 as candidate biomarkers in this disease.

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New Biomarkers in Acute Tubulointerstitial Nephritis: A Novel Approach to a Classic Condition

International Journal of Molecular Sciences ◽

10.3390/ijms21134690 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4690 ◽

Cited By ~ 1

Author(s):

Laura Martinez Valenzuela ◽

Juliana Draibe ◽

Xavier Fulladosa ◽

Juan Torras

Keyword(s):

Acute Kidney Injury ◽

Tubulointerstitial Nephritis ◽

Kidney Injury ◽

Special Focus ◽

Nucleotide Polymorphisms ◽

Acute Tubulointerstitial Nephritis ◽

Non Invasive ◽

Cytokines And Chemokines ◽

Novel Approach ◽

New Biomarkers

Acute tubulointerstitial nephritis (ATIN) is an immunomediated cause of acute kidney injury. The prevalence of ATIN among the causes of acute kidney injury (AKI) is not negligible, especially those cases related to certain drugs. To date, there is a lack of reliable non-invasive diagnostic and follow-up markers. The gold standard for diagnosis is kidney biopsy, which shows a pattern of tubulointerstitial leukocyte infiltrate. The urinalysis findings can aid in the diagnosis but are no longer considered sensitive or specific. Atthe present time, there is a rising attentiveness tofinding trustworthy biomarkers of the disease, with special focus in urinary cytokines and chemokines that may reflect kidney local inflammation. Cell-based tests are of notable interest to identify the exact drug involved in hypersensitivity reactions to drugs, manifesting as ATIN. Certain single-nucleotide polymorphisms in HLA or cytokine genes may confer susceptibility to the disease according to pathophysiological basis. In this review, we aim to critically examine and summarize the available evidence on this topic.

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Acute tubulointerstitial nephritis in children and chronic kidney disease

Archives de Pédiatrie ◽

10.1016/j.arcped.2019.05.002 ◽

2019 ◽

Vol 26 (5) ◽

pp. 290-294 ◽

Cited By ~ 3

Author(s):

S. Clavé ◽

C. Rousset-Rouvière ◽

L. Daniel ◽

M. Tsimaratos

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Tubulointerstitial Nephritis ◽

Acute Tubulointerstitial Nephritis

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Cockayne syndrome with recurrent acute tubulointerstitial nephritis

Pathology International ◽

10.1111/j.1440-1827.2006.02029.x ◽

2006 ◽

Vol 56 (11) ◽

pp. 678-682 ◽

Cited By ~ 8

Author(s):

Satoshi Funaki ◽

Shori Takahashi ◽

Hitohiko Murakami ◽

Kensuke Harada ◽

Hiroshi Kitamura

Keyword(s):

Tubulointerstitial Nephritis ◽

Cockayne Syndrome ◽

Acute Tubulointerstitial Nephritis

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Acute Tubulointerstitial Nephritis in a Patient on Anti-Programmed Death-Ligand 1 Triggered by COVID-19: A Case Report

Canadian Journal of Kidney Health and Disease ◽

10.1177/20543581211014745 ◽

2021 ◽

Vol 8 ◽

pp. 205435812110147

Author(s):

Dimitry Buyansky ◽

Catherine Fallaha ◽

François Gougeon ◽

Marie-Noëlle Pépin ◽

Jean-François Cailhier ◽

...

Keyword(s):

Case Report ◽

Severe Acute Respiratory Syndrome ◽

Tubulointerstitial Nephritis ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

High Dose ◽

Programmed Death Ligand 1 ◽

Acute Tubulointerstitial Nephritis ◽

Programmed Death ◽

Kidney Involvement

Rationale: Immune checkpoint inhibitors are monoclonal antibodies used in the treatment of various types of cancers. The downside of using such molecules is the potential risk of developing immune-related adverse events. Factors that trigger these autoimmune side effects are yet to be elucidated. Although any organ can potentially be affected, kidney involvement is usually rare. In this case report, we describe the first known instance of a patient being treated with an inhibitor of programmed death-ligand 1 (anti-PD-L1, a checkpoint inhibitor) who develops acute tubulointerstitial nephritis after contracting the severe acute respiratory syndrome coronavirus 2. Presenting concerns of the patient: A 62-year-old patient, on immunotherapy treatment for stage 4 squamous cell carcinoma, presents to the emergency department with symptoms of lower respiratory tract infection. Severe acute kidney injury is discovered with electrolyte imbalances requiring urgent dialysis initiation. Further testing reveals that the patient has contracted the severe acute respiratory syndrome coronavirus 2. Diagnosis: A kidney biopsy was performed and was compatible with acute tubulointerstitial nephritis. Interventions: The patient was treated with high dose corticosteroid therapy followed by progressive tapering. Outcomes: Rapid and sustained normalization of kidney function was achieved after completion of the steroid course. Novel findings: We hypothesize that the viral infection along with checkpoint inhibitor use has created a proinflammatory environment which led to a loss of self-tolerance to renal parenchyma. Viruses may play a more important role in the pathogenesis of autoimmunity in this patient population than was previously thought.

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HEART RATE VARIABILITY RELATED TO N95 RESPIRATOR USE IN INTERNS DURING COVID-19 PANDEMIC

10.36106/ijsr/4308359 ◽

2021 ◽

pp. 69-70

Author(s):

Pakanati Sujana ◽

Venkata Mahesh Gandhavalla ◽

K. Prabhakara Rao

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Low Frequency ◽

Protective Equipment ◽

Short Term ◽

Non Invasive ◽

Critical Components ◽

The Individual ◽

N95 Respirators ◽

Respiratory Droplets

Introduction: COVID19 is caused by SARS-CoV-2 which is primarily transmitted through respiratory droplets and contact routes. WHO recommended the use of personal protective equipment (PPE) for prevention and N95 respirators are critical components of PPE. Breathing through N95 respirator will impart stress in the individual and that can be assessed by heart rate variability (HRV). HRV measures the variation in time between each heartbeat controlled by autonomic nervous system (ANS), which is a non invasive reliable index to identify the ANS imbalances. Aims And Objectives: This study is aimed at assessing the HRV of Interns working in COVID19 wards using N95 respirators. Methodology: This study included 100 interns in whom short term HRV was recorded using the standard protocol. Lead II of ECG was recorded using AD instruments (ADI) 8channel polygraph and HRV was analysed using Labchart 8pro software. The recordings were taken before and 1hour after wearing N95 respirator. Results: Overall HRV (SDRR) was found to decrease signicantly after wearing N95 respirator for 1hr (p=0.000). Similarly, indices representing the parasympathetic component ( RMSSD and HF ) were also found to decrease signicantly with the use of N95 respirator. Low frequency (LF) power and LF/HF ratio increased signicantly with N95 respirator use (p=0.000). Conclusion: We conclude that using N95 respirator increased sympathetic activity reecting decreased HRV in our subjects Hence we recommend that it is better to change the duty pattern for interns.

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A Psycho-Pedagogical Framework for Multi-Adaptive Educational Games

International Journal of Game-Based Learning ◽

10.4018/ijgbl.2011010104 ◽

2011 ◽

Vol 1 (1) ◽

pp. 45-58 ◽

Cited By ~ 19

Author(s):

Michael D. Kickmeier-Rust ◽

Elke Mattheiss ◽

Christina Steiner ◽

Dietrich Albert

Keyword(s):

Game Design ◽

Educational Games ◽

Educational Game ◽

Key Factors ◽

Embedded Assessment ◽

Non Invasive ◽

Motivational States ◽

Individual Support ◽

Learning Game ◽

The Individual

One of the trump cards of digital educational games is their enormous intrinsic motivational potential. Although learning game design is often understood on a one-fits-all level, the actual motivational strength of an educational game strongly depends on the individual learners, their very specific goals, preferences, abilities, strength and weakness, personality, and experiences with gaming. Considering motivation being a fragile and constantly changing state, it is important to continuously assess learning and gaming processes and the oscillations of motivation and immersion within a game. With this premise in mind, the authors developed a psycho-pedagogical approach to a non-invasive embedded assessment of motivational states and learning progress, feeding into a dynamic, ontology-driven learner (and gamer) model. To evaluate the approach, the demonstrator games were subject to intensive quantitative and qualitative experimental research. Results show that a meaningful personalization and an individual support are key factors of the success of learning games.

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