Acidosis and acute kidney injury in severe malaria

Natthida Sriboonvorakul,Md Amir Hossain,Nicholas J White,Aniruddha Ghose,Katherine Plewes,Nicholas P J Day,Joel Tarning,Arjen M Dondorp,Yaowalark Sukthana,Sasithon Pukrittayakamee,M Abul Faiz,Kesinee Chotivanich,Stije J Leopold,M Mahtab Uddin Hassan

doi:10.1186/s12936-018-2274-9

Abstract

BackgroundIn severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups. The relationship between plasma acids, urine acids and renal function was investigated in adult patients with acute falciparum malaria.MethodsPlasma and urinary acids which previously showed increased concentrations in proportion to disease severity in patients with severe falciparum malaria were quantified. Patients with uncomplicated malaria, sepsis and healthy volunteers served as comparator groups. Multiple regression and multivariate analysis were used to assess the relationship between organic acid concentrations and clinical syndromes, in particular AKI.ResultsPatients with severe malaria (n = 90), uncomplicated malaria (n = 94), non-malaria sepsis (n = 19), and healthy volunteers (n = 61) were included. Univariate analysis showed that both plasma and creatinine-adjusted urine concentrations of p-hydroxyphenyllactic acid (pHPLA) were higher in severe malaria patients with AKI (p < 0.001). Multiple regression analysis, including plasma or creatinine-adjusted urinary acids, and PfHRP2 as parasite biomass marker as independent variables, showed that pHPLA was independently associated with plasma creatinine (β = 0.827) and urine creatinine (β = 0.226). Principal component analysis, including four plasma acids and seven urinary acids separated a group of patients with AKI, which was mainly driven by pHPLA concentrations.ConclusionsBoth plasma and urine concentrations of pHPLA closely correlate with AKI in patients with severe falciparum malaria. Further studies will need to assess the potential nephrotoxic properties of pHPLA.

Highlights

In severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups
The current study reports a secondary data analysis on plasma and urine organic acids elevated in adult patients with falciparum malaria and sepsis [13, 14], and relates these to organ failure in severe malaria, in particular AKI
The concentrations of plasma and corrected urinary lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA), and p-hydroxyphenyllactic acid (pHPLA) were higher in patients with severe malaria compared to Severe malaria N = 90

Summary

Introduction

In severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups. The major manifestations of severe malaria, which independently predict fatal outcome in both adults and children, include coma (cerebral malaria), acidosis and renal dysfunction [2,3,4,5]. Adjusting the plasma concentration for plasma creatinine only corrects for concomitant renal dysfunction if the acid or biomarker has similar renal clearance dynamics as creatinine, including similar renal filtration, re-absorption and secretion. For many biomarkers these properties have not been assessed

Methods

Results

Discussion

Conclusion