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 'mild, 'moderate' and 'severe' AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-for-trend 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.
authors.forename: Katherine
authors.initials: K
authors.lastname: Plewes
authors.forename: Annick A
authors.initials: AA
authors.lastname: Royakkers
authors.forename: Josh
authors.initials: J
authors.lastname: Hanson
authors.forename: Md Mahtab Uddin
authors.initials: MM
authors.lastname: Hasan
authors.forename: Shamsul
authors.initials: S
authors.lastname: Alam
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Ghose
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maude
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Stassen
authors.forename: Prakaykaew
authors.initials: P
authors.lastname: Charunwatthana
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Gareth D H
authors.initials: GD
authors.lastname: Turner
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. arjen@tropmedres.ac.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016778:Malaria, Falciparum / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D059208:Parasite Load; D015800:Protozoan Proteins / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D015415:Biomarkers; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D055293:Receptors, Urokinase Plasminogen Activator