ABSTRACT

Background and Aim: Plasmodium falciparum malaria remains a major cause of severe disease and mortality, with acute kidney injury (AKI) representing an important complication associated with poor clinical outcomes. Although conventional blood-based methods remain essential for malaria diagnosis, they primarily establish parasite infection and provide limited information on evolving host responses and renal injury. Urine represents an attractive complementary biological matrix because it can be collected non-invasively and repeatedly and may contain parasite-derived products, metabolites, inflammatory mediators, hemolysis-associated molecules, and biomarkers of structural kidney injury. This review summarizes current evidence on urinary biomarkers in falciparum malaria, with particular emphasis on their biological relevance, relationship with renal involvement, diagnostic potential, and clinical applicability. Available evidence suggests that urinary biomarkers fall into three interconnected domains: parasite-related signals, host response indicators, and structural renal injury markers. Parasite-derived antigens, particularly histidine-rich protein 2, and malaria-associated urinary metabolites have demonstrated potential for non-invasive detection, although their diagnostic performance and specificity remain variable. Dipstick abnormalities may reflect hemolysis, renal involvement, and hepatobiliary dysfunction but are not specific to malaria. Urinary inflammatory and immune-related mediators have shown preliminary associations with parasitemia and disease severity, whereas evidence supporting their routine clinical application remains limited. Structural tubular injury biomarkers, particularly neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, appear promising for detecting malaria-associated AKI and may provide information beyond conventional creatinine-based assessment. However, the available literature is characterized by small study populations, heterogeneous clinical settings, differences in specimen processing and analytical platforms, inconsistent biomarker thresholds, and limited external validation. Urinary biomarkers therefore represent promising complementary tools rather than replacements for established blood-based malaria diagnostics. Standardized prospective multicenter studies, particularly in malaria-endemic and resource-limited settings, are needed to determine their diagnostic, prognostic, and clinical utility.

Keywords: acute kidney injury, falciparum malaria, kidney injury molecule-1, malaria diagnostics, neutrophil gelatinase-associated lipocalin, renal biomarkers, tubular injury, urinary biomarkers.