Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria

Katherine Plewes; Annick Royakkers; Joshua Hanson; Md Mahtab Uddin Hasan; Shamsul Alam; Aniruddha Ghose; Richard Maude; Pauline Stassen; Prakaykaew Charunwatthana; Sue J Lee; Gareth Turner; Arjen Dondorp; Marcus Schultz

doi:10.1186/1475-2875-13-91

Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria

Katherine Plewes, Annick Royakkers, Joshua Hanson, Md Mahtab Uddin Hasan, Shamsul Alam, Aniruddha Ghose, Richard Maude, Pauline Stassen, Prakaykaew Charunwatthana, Sue J Lee, Gareth Turner, Arjen Dondorp, Marcus Schultz

Global and Tropical Health

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Abstract

Background: Acute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 (PfHRP2), as a measure of sequestered parasite burden, with AKI in severe malaria.

Methods: Admission plasma suPAR and PfHRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n = 137). Patients were stratified according to AKI severity based on admission creatinine clearance.

Results: A total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into ‘mild, ‘moderate’ and ‘severe’ AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-fortrend P <0.0001) and correlated with other markers of renal dysfunction. Admission plasma suPAR and PfHRP2 concentrations were higher in patients who later required RRT (P <0.0001 and P = 0.0004, respectively). In a multivariate analysis, both increasing suPAR and PfHRP2 were independently associated with increasing urine neutrophil gelatinase-associated lipocalin concentration, a marker of acute tubular necrosis (β = 16.54 (95% CI 6.36- 26.71) and β = 0.07 (0.02-0.11), respectively).

Conclusions: Both sequestered parasite burden and immune activation contribute to the pathogenesis of AKI in severe falciparum malaria.

Original language	English
Article number	91
Pages (from-to)	1-10
Number of pages	10
Journal	Malaria Journal
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/1475-2875-13-91
Publication status	Published - 2014

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Plewes, K., Royakkers, A., Hanson, J., Hasan, M. M. U., Alam, S., Ghose, A., Maude, R., Stassen, P., Charunwatthana, P., Lee, S. J., Turner, G., Dondorp, A., & Schultz, M. (2014). Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria. Malaria Journal, 13(1), 1-10. Article 91. https://doi.org/10.1186/1475-2875-13-91

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title = "Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria",

abstract = "Background: Acute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 (PfHRP2), as a measure of sequestered parasite burden, with AKI in severe malaria.Methods: Admission plasma suPAR and PfHRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n = 137). Patients were stratified according to AKI severity based on admission creatinine clearance.Results: A total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into {\textquoteleft}mild, {\textquoteleft}moderate{\textquoteright} and {\textquoteleft}severe{\textquoteright} AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-fortrend P <0.0001) and correlated with other markers of renal dysfunction. Admission plasma suPAR and PfHRP2 concentrations were higher in patients who later required RRT (P <0.0001 and P = 0.0004, respectively). In a multivariate analysis, both increasing suPAR and PfHRP2 were independently associated with increasing urine neutrophil gelatinase-associated lipocalin concentration, a marker of acute tubular necrosis (β = 16.54 (95% CI 6.36- 26.71) and β = 0.07 (0.02-0.11), respectively).Conclusions: Both sequestered parasite burden and immune activation contribute to the pathogenesis of AKI in severe falciparum malaria.",

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author = "Katherine Plewes and Annick Royakkers and Joshua Hanson and Hasan, {Md Mahtab Uddin} and Shamsul Alam and Aniruddha Ghose and Richard Maude and Pauline Stassen and Prakaykaew Charunwatthana and Lee, {Sue J} and Gareth Turner and Arjen Dondorp and Marcus Schultz",

year = "2014",

doi = "10.1186/1475-2875-13-91",

language = "English",

volume = "13",

pages = "1--10",

journal = "Malaria Journal",

issn = "1475-2875",

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TY - JOUR

T1 - Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria

AU - Plewes, Katherine

AU - Royakkers, Annick

AU - Hanson, Joshua

AU - Hasan, Md Mahtab Uddin

AU - Alam, Shamsul

AU - Ghose, Aniruddha

AU - Maude, Richard

AU - Stassen, Pauline

AU - Charunwatthana, Prakaykaew

AU - Lee, Sue J

AU - Turner, Gareth

AU - Dondorp, Arjen

AU - Schultz, Marcus

PY - 2014

Y1 - 2014

N2 - Background: Acute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 (PfHRP2), as a measure of sequestered parasite burden, with AKI in severe malaria.Methods: Admission plasma suPAR and PfHRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n = 137). Patients were stratified according to AKI severity based on admission creatinine clearance.Results: A total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into ‘mild, ‘moderate’ and ‘severe’ AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-fortrend P <0.0001) and correlated with other markers of renal dysfunction. Admission plasma suPAR and PfHRP2 concentrations were higher in patients who later required RRT (P <0.0001 and P = 0.0004, respectively). In a multivariate analysis, both increasing suPAR and PfHRP2 were independently associated with increasing urine neutrophil gelatinase-associated lipocalin concentration, a marker of acute tubular necrosis (β = 16.54 (95% CI 6.36- 26.71) and β = 0.07 (0.02-0.11), respectively).Conclusions: Both sequestered parasite burden and immune activation contribute to the pathogenesis of AKI in severe falciparum malaria.

AB - Background: Acute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 (PfHRP2), as a measure of sequestered parasite burden, with AKI in severe malaria.Methods: Admission plasma suPAR and PfHRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n = 137). Patients were stratified according to AKI severity based on admission creatinine clearance.Results: A total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into ‘mild, ‘moderate’ and ‘severe’ AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-fortrend P <0.0001) and correlated with other markers of renal dysfunction. Admission plasma suPAR and PfHRP2 concentrations were higher in patients who later required RRT (P <0.0001 and P = 0.0004, respectively). In a multivariate analysis, both increasing suPAR and PfHRP2 were independently associated with increasing urine neutrophil gelatinase-associated lipocalin concentration, a marker of acute tubular necrosis (β = 16.54 (95% CI 6.36- 26.71) and β = 0.07 (0.02-0.11), respectively).Conclusions: Both sequestered parasite burden and immune activation contribute to the pathogenesis of AKI in severe falciparum malaria.

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KW - creatinine

KW - neutrophil gelatinase associated lipocalin

KW - Plasmodium falciparum histidine rich protein 2

KW - protein

KW - unclassified drug

KW - urokinase receptor

KW - acute kidney failure

KW - acute kidney tubule necrosis

KW - adult

KW - article

KW - cell activation

KW - creatinine clearance

KW - disease severity

KW - exploratory research

KW - female

KW - human

KW - kidney dysfunction

KW - major clinical study

KW - malaria falciparum

KW - male

KW - mononuclear cell

KW - parasite load

KW - protein blood level

KW - Acute Kidney Injury

KW - Adolescent

KW - Adult

KW - Animals

KW - Antigens, Protozoan

KW - Biological Markers

KW - Female

KW - Humans

KW - Leukocytes, Mononuclear

KW - Malaria, Falciparum

KW - Male

KW - Middle Aged

KW - Parasite Load

KW - Protozoan Proteins

KW - Receptors, Urokinase Plasminogen Activator

KW - Young Adult

U2 - 10.1186/1475-2875-13-91

DO - 10.1186/1475-2875-13-91

M3 - Article

SN - 1475-2875

VL - 13

SP - 1

EP - 10

JO - Malaria Journal

JF - Malaria Journal

IS - 1

M1 - 91

ER -

Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria

Abstract

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