Nuclear factor kappa B in urine sediment: a useful indicator to detect

acute kidney injury in Plasmodium falciparum malaria

Author: Chuchard Punsawad and Parnpen Viriyavejakul Malaria Journal 2014, 13:84 doi:10.1186/1475-2875-13-84

speaker：邱以涵advisor：張永宗Date: 2015.04.07

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CONTENTS

• ABSTRACT• MALARIA LABORTARY DIAGNOSIS• INTRODUCE ACUTE KIDNEY INJURY• BIOMARKERS OF RENAL FUNCTION

• METHODS• RESULTS• CONCLUSIONS• TAKE HOME MESSAGE

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ABSTRACT

• Acute kidney injury (AKI) is one of the major complications of Plasmodium falciparum malaria.

• Activation of transcription factor nuclear factor kappa B (NF-κB) involved in the development of progressive renal inflammatory diseases.

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THE AIM of THE STUDY was to determine whether urinary sediment NF-κB p65 can act as a biomarker for AKI in patients with P. falciparum malaria.

NF-κB P65

P. falciparum

malaria

biomarker

acute kidney injury

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MALARIA LABORTARY DIAGNOSIS

• Microscopy (morphologic analysis) This technique remains the gold standard for

laboratory confirmation of malaria.

• Molecular Diagnosis PCR is for confirming the species of malaria after the

diagnosis either smear microscopy or RDT.

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• Antigen Detection Rapid Diagnostic Test(RDTs)

• Serology Using either indirect immunofluorescence (IFA) or

enzyme-linked immunosorbent assay (ELISA).

Rapid Diagnostic Test(RDTs)

1) accuracy: >99%2) read Time: 5-10 minutes3) easy to use and carry4) competitive price

 

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Disadvantages

• The RDT may not be able to detect some infections with lower numbers of malaria parasites.

ACUTE KIDNEY INJURY

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CAUSES OF ACUTE KIDNEY INJURY

hypoperfusion

30~60%

20~40%

1~10%

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• Renal tubular epithelial cells and muddy brown casts(granular casts) suspect acute tubular necrosis.

Possible Urine Sediment Findings in Acute Kidney Injury

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Possible Urine Sediment Findings in Acute Kidney Injury

• Urinary eosinophils suggest acute interstitial nephritis.

• RBC casts indicate glomerulonephritis or vasculitis.

Biomarkers of Renal Function

Biomarker Type Biomarker

Functional marker Serum creatinine

Up-regulated proteins Neutrophil gelatinase-associated lipocalin (NGAL)Kidney injury molecule 1 (KIM-1)Interleukin 18 (IL-18)

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Creatinine

• At present, serum creatinine, which is used to measure the glomerular filtration rate (GFR), is the most commonly used marker of renal function.

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Why we search for new biomarker?

• Serum creatinine is a delayed and unreliable indicator of acute kidney injury (AKI).

a) The creatinine level is influenced by multiple non-renal factors.

b) Serum creatinine measurement does not allow differentiation between hemodynamically mediated changes in renal function.

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THE AIM of THE STUDY was to determine whether urinary sediment NF-κB p65 can act as a biomarker for AKI in patients with P. falciparum malaria.

NF-κB P65

P. falciparum

malaria

biomarker

acute kidney injury

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NF-κB P65

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METHODSMEASUREMENT OF URINARY SEDIMENT NF- p65 LEVELS

Phospho NF-κB P65 mouse monoclonal antibody

Phospho NF-κB P65 rabbit monoclonal antibody

OD:450nm

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STATISTICAL ANALYSISWITH AKI

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WITH AKI

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RESULTSLEVELS OF NF-KB P65 IN THE URINARY

SEDIMENT CELLSWITH AKI

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DAY 0 DAY 7

CREATININE

BLOOD UREA NITROGEN

URINE WBC

Positive correlation

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• A significant positive correlation was found between NF-κB p65 in the urinary sediment cells and serum Cr.

DAY 0 DAY 7Rs:0.9000; p:0.037 Rs: 0.975; p:<0.005

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CONCLUSIONS

• the urinary level of NF-κB p65 has a potential role as a disease biomarker for renal tubular epithelial cells and AKI among complicated P. falciparum malaria patients.

• Early diagnosis and prompt management including dialysis can reduce mortality .

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Research associated with Plasmodium falciparum

andNF-κB p65

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Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear

factor kappa B expressionParnpen Viriyavejakul12*, Vasant Khachonsaksumet1 and Chuchard Punsawad3

Malaria Journal 2014, 13:106 doi:10.1186/1475-2875-13-106

• ResultsHyperplastic Kupffer cells and portal tract inflammation are two main features found in the liver tissues of severe P. falciparum malaria cases. In addition, NF-κB is associated with Kupffer cells and lymphocyte apoptosis in severe P. falciparum malaria.

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Take home messagethe urinary level of NF-κB p65 has a potential role as a disease biomarker in AKI among complicated P. falciparum malaria patients.

NF-κB P65

P. falciparum

malaria

biomarker

acute kidney injury

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ACUTE KIDNEY INJURY腎臟病理標本顯示已標記的皮質為蒼白色、對比於尚存的髓質組織的暗色區。

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Recent studies show that NF-κB p65 activation has also been detected in peripheral blood mononuclear cells (PBMCs) from

complicated P. falciparum malaria patients.

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