Comparative analysis of acute kidney injury in tropical infections: A retrospective cohort study

Introduction

Acute kidney injury (AKI) is a commonly observed and potentially fatal complication that arises in association with several tropical infectious diseases. It is especially prevalent in regions with high disease burden such as South and Southeast Asia, sub-Saharan Africa and Latin America. Infections such as dengue, leptospirosis, malaria and scrub typhus can trigger AKI through a variety of mechanisms, including direct kidney involvement by infectious agents, immune-mediated damage, intravascular haemolysis, muscle breakdown (rhabdomyolysis), fluid loss and widespread inflammation.

AKI in the context of these infections is a major contributor to increased illness severity and death, particularly when detection and treatment are delayed. Although these tropical diseases often co-exist in similar geographical areas and share overlapping clinical symptoms, their manifestation can differ significantly.

We evaluate and contrast the frequency, clinical features, biochemical changes, underlying risk factors and patient outcomes in these four diseases.

Materials and methods

Our retrospective observational study was conducted at a tertiary care centre. A total of 149 patients were included comprising 34 with dengue, 36 with leptospirosis, 34 with malaria and 45 with scrub typhus. Patients were diagnosed with AKI based on standard criteria, which include elevated serum creatinine and/or reduced urine output (refer Kidney Disease: Improving Global Outcomes (KDIGO)). The diagnoses of the underlying tropical infections were confirmed through appropriate laboratory investigations, typically NS1 antigen and immunoglobulin M (IgM) serology for dengue, microscopic agglutination test for leptospirosis, peripheral blood smear or antigen detection for malaria and IgM enzyme-linked immunosorbent assay for scrub typhus.

Clinical and laboratory data were collected retrospectively from hospital records, including patient demographics, comorbidity (such as hypertension and diabetes), admission laboratory values, dialysis requirements and outcomes. All patients were observed retrospectively for a duration of three months to assess renal recovery, development of chronic kidney disease (CKD) or mortality. CKD was defined as an estimated glomerular filtration rate of ≤60 mL/min/1.73 m² persisting for more than three months. Data analysis involved descriptive statistics, with continuous variables expressed as mean ± standard deviation or median (interquartile range), and categorical variables as percentages. Comparative analysis was performed to evaluate differences in clinical characteristics, biochemical abnormalities and outcomes across the four infection groups. Additionally, the presence of potential risk factors such as age >60 years, male sex, hypertension, leucocytosis, thrombocytopenia and elevated serum creatinine was assessed in relation to mortality and CKD development. Ethical approval for this study was obtained from the institutional review board, and all patient data were handled in accordance with ethical standards to ensure confidentiality.

Results

See Tables 1 to 3, and Figs. 1 and 2.

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Figure 1.

Clinical outcomes by disease.

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Figure 2.

Odds ratios by risk type.

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Table 1.

Baseline characteristics of patients.

Variable	Leptospirosis (N = 36)	Malaria (N = 34)	Scrub typhus (N = 45)	Dengue (N = 34)
Age (years)	56.0 (45.0–66.0)	37.0 (24.0–59.0)	61.0 (48.0–72.0)	46.5 (30.0–59.0)
Sex (% male)	80.6% (29/36)	67.6% (23/34)	53.3% (24/45)	44.1% (15/34)
Comorbidity (% yes)	19.4% (7/36)	5.9% (2/34)	22.2% (10/45)	17.6% (6/34)
Admission creatinine (µmol/L)	464 (183–619)	133 (124–389)	383 (148–541)	150 (124–362)
WBC count (×109/L)	14 (10.3–18.2)	7.1 (4.3–12)	9.3 (7.9–12.9)	7.7 (4–14.7)
Platelet count (×109/L)	120 (55–230)	80 (21–154)	150 (140–200)	64 (29–190)
Total bilirubin (µmol/L)	18.8 (12.0–37.6)	20.5 (8.6–42.8)	23.9 (12.0–42.8)	13.7 (8.6–23.9)
SGOT (U/L)	56 (47–64)	45 (28–70)	64 (43–87)	61 (31–135)
SGPT (U/L)	40 (34–59)	38 (21–78)	42 (31–85)	44 (25–92)
ALP (U/L)	115 (102–158)	91 (72–108)	102 (67–147)	89 (56–123)
No. of haemodialysis sessions	0 (0–4)	0 (0–2)	0 (0–4)	0 (0–2)
Outcome (% recovered)	72.2% (26/36)	91.2% (31/34)	66.7% (30/45)	85.3% (29/34)

ALP: alkaline phosphatase; SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; WBC: white blood cells.

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Table 2.

Morbidity, mortality, recovery and dialysis in the four tropical diseases.

Outcome	Dengue (N = 38)	Leptospirosis (N = 36)	Malaria (N = 34)	Scrub typhus (N = 45)
Mortality	5.3% (2/38)	11.1% (4/36)	5.9% (2/34)	13.3% (6/45)
CKD	7.9% (3/38)	27.8% (10/36)	8.8% (3/34)	20.0% (9/45)
Recovered	86.8% (33/38)	61.1% (22/36)	85.3% (29/34)	66.7% (30/45)
Mean dialysis sessions	0.8	3.2	1.1	2.4

CKD: chronic kidney disease.

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Table 3.

Risk factors for morbidity and mortality.

Risk factor	CKD risk (OR)	Mortality risk (OR)	Notes
Age ≥60 years	3.2 (2.1–4.8)	2.8 (1.9–4.1)
Hypertension	4.1 (2.7–6.3)	3.5 (2.3–5.4)	Present in 91% of leptospirosis CKD cases and 85% of deaths
Diabetes	3.8 (2.5–5.7)	2.9 (1.8–4.6)	67% higher CKD progression in diabetic patients
Admission creatinine >177 μmol/L	5.6 (3.9–8.1)	4.2 (2.9–6.2)	92% predictive value for CKD development
Platelet <50 × 109//L	2.4 (1.6–3.7)	3.1 (2.1–4.8)	Strongest predictor in scrub typhus (p < 0.001)
Bilirubin >34 μmol/L	1.9 (1.3–2.8)	2.7 (1.9–4.0)	Hepatic dysfunction compounded renal risk
Dialysis required	6.8 (4.7–9.8)	5.2 (3.6–7.5)	Patients needing haemodialysis had 8× higher mortality
Leptospirosis diagnosis	4.3 (3.0–6.2)	2.1 (1.4–3.2)	Highest CKD risk among all diseases
Scrub typhus diagnosis	2.7 (1.8–4.0)	3.3 (2.3–4.9)	Highest mortality risk

CKD: chronic kidney disease; OR: odds ratio.

Discussion

Leptospirosis was found to be associated with the highest CKD risk, and the highest dialysis burden. The pathophysiology of AKI in leptospirosis primarily involves direct tubular damage, vasculitis and interstitial nephritis caused by Leptospira interrogans. This bacterium directly invades the renal tubular epithelium, leading to cellular apoptosis and tubulointerstitial inflammation. Additionally, systemic hypotension, rhabdomyolysis and hyperbilirubinaemia further compound renal injury. ¹

These findings align with a similar study. ² A strong association between elevated creatinine on admission and both CKD and mortality in our cohort is consistent with the KDIGO risk stratification system. ³

Scrub typhus had the highest mortality rate and a notable CKD rate. The mechanism of AKI in scrub typhus involves widespread endothelial injury due to Orientia tsutsugamushi, leading to vasculitis, tubular necrosis and interstitial inflammation. The cytokine storm and capillary leak syndrome contribute to renal hypoperfusion and direct injury. ⁴

We found that platelet counts <50x10⁹/L were particularly predictive of mortality in this group (odds ratio 3.1), highlighting severe systemic involvement as found in patients with multi-organ dysfunction, especially those with thrombocytopenia and jaundice. ⁵ However, a two-thirds full recovery rate suggests that early doxycycline therapy can reverse organ dysfunction if started promptly. ⁶

Malaria had a mortality rate half that of leptospirosis and CKD risk a third requiring fewer dialysis sessions. AKI in malaria is most often associated with Plasmodium falciparum, due to cytoadherence of infected erythrocytes, leading to microvascular obstruction, haemolysis and acute tubular necrosis. Volume depletion and cytokine-mediated injury also contribute.^7,8

The majority of our patients recovered without progressing to CKD, suggesting a relatively reversible AKI pattern when managed early but the lower incidence of comorbidity may have contributed to the better prognosis.

Dengue showed the lowest mortality and CKD rate. AKI in dengue results from a combination of hypovolaemia, rhabdomyolysis, direct viral nephropathy and cytokine-mediated injury. Capillary leakage and severe thrombocytopoenia may also cause intrarenal ischaemia. ⁹

Most cases of dengue-associated AKI are mild and self-limiting, with full renal recovery in ≥80% of cases. ¹⁰ However, severe thrombocytopenia (<50 × 10⁹/L), seen in many was a notable risk factor for poor outcomes. ¹¹

Clinical implications

Risk factors such as advanced age, with 78% of deaths and 82% of CKD cases and co-existing hypertension with 91% of CKD cases are notable risk amplifiers in leptospiral AKI. Diabetes, elevated creatinine (>177 µmol/L) at admission, severe thrombocytopenia (<50 × 10⁹/L) and jaundice were independently associated with progression to CKD and increased mortality. Recognising these predictors early can help triage patients who require intensive monitoring and early renal support. These are inexpensive and routinely available investigations, making them practical tools for early risk assessment in primary and secondary healthcare settings. Early initiation of antibiotics in scrub typhus, and aggressive fluid management in leptospirosis may significantly alter outcomes.

The development of CKD in a significant subset of patients highlights the importance of post-discharge follow-up. Structured outpatient programmes focusing on renal function monitoring and blood pressure control may reduce long-term complications.

Limitations

Being retrospective and single-centre, the findings may not be generalisable to other endemic settings. The modest sample size in each disease subgroup could have limited statistical power. Finally, residual confounding from unmeasured clinical or treatment factors cannot be excluded.

Conclusion

This disease-specific analysis highlights that leptospirosis and scrub typhus carry the greatest risk of adverse renal outcomes and mortality, primarily due to their aggressive pathophysiological mechanisms and association with comorbidities. In contrast, dengue and malaria tend to have favourable renal recovery, especially when diagnosed early and managed effectively. Identifying high-risk patients using clinical markers such as age, admission creatinine, thrombocytopoenia and comorbidities is essential for guiding early interventions.