What is the association between laboratory markers (platelet count, transaminases (liver enzymes), albumin, C-Reactive Protein (CRP)) and Acute Kidney Injury (AKI) severity in patients with Tropical Acute Febrile Illness?

Association of Laboratory Markers with AKI Severity in Tropical Acute Febrile Illness

Laboratory markers including thrombocytopenia, elevated transaminases, hypoalbuminemia, and increased CRP are significantly associated with increased severity of AKI in tropical acute febrile illness, with these markers serving as important predictors of poor outcomes including mortality.

Epidemiology and Significance

• Tropical Acute Febrile Illness (TAFI) is a major cause of Acute Kidney Injury (AKI) with approximately 41-54% of TAFI patients developing AKI, making it a significant contributor to morbidity and mortality 1, 2
• The most common etiologies of TAFI include malaria (particularly vivax malaria), leptospirosis, dengue fever, scrub typhus, and enteric fever 1
• Leptospirosis is associated with the highest nephrotoxicity and risk of severe AKI (stages 2 and 3), while dengue fever is the most common cause of AKI stage 1 1

Laboratory Markers Associated with AKI Severity

Platelet Count

• Thrombocytopenia (platelet count <150 × 10^9/L) is significantly associated with AKI development and severity in TAFI 3, 4
• In dengue-associated AKI, severe thrombocytopenia correlates with progression to more advanced stages of kidney injury 4
• Platelet count serves as both a diagnostic and prognostic marker, with lower counts associated with higher mortality and need for renal replacement therapy (RRT) 5

Transaminases (Liver Enzymes)

• Elevated transaminases, particularly SGPT (ALT) and alkaline phosphatase (ALP), are significantly higher in TAFI patients who develop AKI compared to those without AKI 4
• Severe transaminitis (SGPT: 450 vs 144 in non-AKI, p=0.001; ALP: 207 vs 42 in non-AKI, p=0.001) is strongly associated with AKI development 4
• The degree of transaminase elevation correlates with AKI severity, with significantly different levels observed between mild, moderate, and severe AKI subgroups (p=0.042 for SGPT, p=0.013 for ALP) 4

Albumin

• Hypoalbuminemia is a consistent finding in TAFI patients with AKI (mean albumin 2.65 g/dL in AKI vs 3.09 g/dL in non-AKI patients, p<0.001) 4
• Lower albumin levels correlate with increasing severity of AKI and are associated with higher mortality 3, 4
• While albumin has historically been used as a nutritional marker, in the context of acute illness it primarily reflects the inflammatory state rather than nutritional status 5

C-Reactive Protein (CRP)

• Elevated CRP is significantly associated with AKI development and progression in TAFI 6
• The ratio of CRP to prealbumin (CRP/prealbumin) is a particularly strong predictor of mortality in AKI patients, independent of illness severity 6
• CRP/prealbumin ratio shows a dose-response relationship with mortality risk, with hazard ratios of 1.00 (reference), 1.85,2.25, and 3.89 for increasing quartiles (p=0.01 for trend) 6

Integrated Assessment of Laboratory Markers

• Combined assessment of inflammatory (CRP) and nutritional markers (albumin, prealbumin) provides superior prognostic information compared to individual parameters 6
• The ADQI (Acute Disease Quality Initiative) consensus recommends combining clinical assessment with biomarkers to optimize patient triage and intervention timing 5
• A combination of damage and functional biomarkers, along with clinical information, improves diagnostic accuracy of AKI and helps assess severity 5

Risk Factors and Predictors of Severe AKI in TAFI

• Male gender (AOR 3.1; 95% CI 1.3-7.4), respiratory failure (AOR 4.6; 95% CI 1.5-14.1), hyperbilirubinemia (AOR 2.4; 95% CI 1.1-4.9), and obesity (AOR 2.9; 95% CI 1.4-6) are independent risk factors for AKI in TAFI 3
• Laboratory abnormalities including leukocytosis, metabolic acidosis, and proteinuria are significantly more common in TAFI patients who develop AKI 3
• Hypotension, coexisting viral hepatitis, sepsis, and multiple organ dysfunction syndrome are associated with increased risk of AKI in dengue fever 4

Clinical Implications and Management

• Early identification of laboratory abnormalities can help predict AKI development and guide preventive interventions 5, 3
• Patients with severe laboratory abnormalities (thrombocytopenia, elevated transaminases, hypoalbuminemia, high CRP) should be closely monitored for AKI progression 3
• Approximately 10-20% of TAFI patients with AKI require renal replacement therapy, with the need for RRT being highest in leptospirosis 1, 3
• In-hospital mortality is significantly higher in TAFI patients who develop AKI (p=0.005), with all deaths in one study occurring exclusively in the AKI group 3, 4

Future Directions

• The ADQI consensus highlights the need for further research on combining validated biomarkers to improve detection of AKI etiology and management 5
• Investigating the role of serial biomarker testing compared to single measurements may provide better prognostic information 5
• Developing specific biomarker panels for tropical infections could help in earlier identification and targeted management of AKI in TAFI 5