European Journal of Cardiovascular Medicine

Acute kidney injury (AKI) remains a critical challenge for nephrologists, especially in tropical regions where infectious diseases significantly contribute to its burden. Despite advancements in diagnostic tools, therapeutic interventions,¹ and dialysis technology, mortality rates associated with AKI have remained largely unchanged over the past five decades.² This stagnation underscores the severity of the condition, with studies showing that nearly 60% of critically ill patients with AKI succumb during hospitalization, and approximately 13% of survivors become dialysis-dependent³. Moreover, among those who recover, 41% develop residual renal insufficiency, and the five-year survival rate is only about 50%. These figures illustrate not only the profound clinical impact of AKI but also the economic and infrastructural strain it imposes on healthcare systems.In tropical and subtropical regions,⁴ AKI is frequently associated with acute febrile illnesses (AFI), including infections such as malaria, dengue fever, leptospirosis, typhoid, and scrub typhus. These illnesses often present with thrombocytopenia (a low platelet count), which complicates the clinical picture and increases the risk of renal complications. The emergence and re-emergence of these infections in non-tropical countries, influenced by global warming and international travel, have reignited global interest in understanding the interplay between these diseases and AKI.⁵ However, reliable data on the incidence and outcomes of AKI in this context remain limited due to inconsistent definitions of AKI and referral biases in tertiary care reports.The pathophysiology of AKI in patients with AFI and thrombocytopenia is multifactorial and not yet fully understood. Hypovolemia, often a consequence of fever-induced dehydration, can reduce renal perfusion and impair waste clearance.⁶ Direct invasion of renal tissues by infectious agents may lead to cellular injury and diminished kidney function. Furthermore, systemic inflammation and immune-mediated damage can exacerbate renal impairment.⁷ These mechanisms act synergistically, making early detection and intervention crucial. However, conventional biomarkers such as serum creatinine may not reflect early renal dysfunction accurately, particularly in acutely ill patients, thereby delaying diagnosis and appropriate management.In India, comprehensive national data on AKI in the setting of AFI and thrombocytopenia is scarce. Most existing studies are limited to isolated centres of excellence and focus narrowly on specific diseases⁷. Recent data suggest that renal failure occurs in 41.3% of cases involving infections such as scrub typhus, dengue, leptospirosis, and malaria, with an associated mortality rate of 12.1%. These findings highlight an urgent need to improve diagnostic and therapeutic strategies in such patients to reduce morbidity and in-hospital mortality. Compounding the issue, patients often present with non-specific symptoms like fever, myalgia, and rash, which can obscure the early signs of AKI⁸.This underscores the importance of a thorough understanding of the risk factors, clinical manifestations, and optimal treatment approaches for AKI in the context of acute febrile illnesses with thrombocytopenia. This study aims to elucidate the spectrum of AKI in such patients and to contribute to the development of timely, effective interventions to improve outcomes in this vulnerable population.

AIM

To evaluate the clinical profile and outcomes of acute kidney injury in patients with tropical acute febrile illness at Mahatma Gandhi Medical College, Jaipur.

This hospital-based prospective observational study will be conducted over a period of 18 months following approval from the Institutional Ethics Committee (IEC) at Mahatma Gandhi Medical College and Hospital, Jaipur. The study aims to evaluate the clinical profile and outcomes of acute kidney injury (AKI) in patients presenting with tropical acute febrile illnesses (AFI). Prior to enrollment, written and informed consent will be obtained from all participants. The inclusion criteria for the study are: all patients aged between 18 and 65 years admitted with AFI without any prior history of renal dysfunction, of either gender, who have provided written informed consent. Patients will be excluded from the study if they have a known history of renal disease, are diagnosed with chronic infections such as tuberculosis, develop AKI due to non-infectious causes, are immunocompromised or immunosuppressed, are pregnant females, or are above the age of 65 years.

Table 1: Gender wise distribution of the study

Majority were male (71.5%), showing possible gender-related exposure or healthcare- seeking differences.

Figure 1,2:AKI wise distribution of the study and Stage AKI wise distribution of the study

40.8% developed AKI, which is significantly high and indicates the nephrotoxic potential of these illnesses.Majority had stage I AKI (53.8%), but a concerning number also progressed to stage II (35.8%) and stage III (10.5%).

Table 2: Final Diagnosis wise distribution of the study

Scrub typhus (38.5%) and dengue fever (53.5%) were the most prevalent infections.

A diverse spectrum of tropical illnesses was represented, each potentially contributing to AKI.

Table 3: Comparison of Dengue and AKI cases and between Malaria and AKI cases

AKI was significantly more prevalent in dengue-positive patients (82.1% vs 33.7%, p=0.001).Suggests a strong association between dengue and AKI.0.9% Malaria positives cases were found in AKI group and 6.5% Malaria positives cases were found in non-AKI group. The data shows a statistically significant association with AKI (p=0.01).

Table 4: Comparison of Scrub typhoid and AKI cases and between Enteric Fever and AKI cases

Unexpectedly, scrub typhus-positive patients had a lower AKI prevalence (16.1%) than negatives (83.9%), which is statistically significant (p=0.001).May reflect misclassification or delayed diagnosis.Paradoxically, widal-positive cases had significantly lower AKI cases than non-AKI cases (0.9%vs 99.1%, p=0.001).

Table 5: Comparison of Dengue and AKI stages and between Malaria and AKI stages

Higher AKI stages (I-III) were predominantly dengue-positive, with stage I at 94.7% positivity (p=0.01). Reinforces dengue's role in severity of AKI.Increasing severity of AKI correlated with decreased malaria positivity (p=0.01). Again, suggests malaria is unlikely to be a major AKI driver here.

Table 6: Comparison of Scrub typhoid and AKI stages and between Enteric Fever and AKI stages

Scrub-positive patients had fewer high-stage AKI cases, indicating a less severe renal involvement in scrub typhus (p=0.01).Enteric positive patients had lower severity in AKI [stage I=2.1%], suggesting that enteric fever is associated with lower possibility of AKI in this cohort(p=0.01).

Table 7: Outcome Of Acute Kidney Injury in Tropical Acute Febrile Illness the Need of Dialysis in Patients with Acute Kidney Injury

10.3% cases required dialysis and 89.6% cases did not required dialysis

Table 8: Comparison Of Serum Creatinine Value & Urine Output Of Day 1 & Day Of Discharge

Serum creatinine and urine output were showed improvement on discharge day.

This study found that 71.5% of the cohort were male, while only 28.5% were female. This significant male predominance likely reflects differences in exposure patterns, health- seeking behavior, and perhaps occupational hazards⁹. In rural and semi-urban Indian contexts, males are more likely to be involved in outdoor labor—farming, construction, or manual work—that increases exposure to vectors like mites (scrub typhus), mosquitoes (dengue), and unsanitary water sources (leptospirosis, enteric fever).¹⁰

Scrub typhus (38.5%) and dengue fever (53.5%) were the most common infections, both known to cause acute kidney injury (AKI) through mechanisms like vasculitis and vascular leakage. The study highlights the overlapping nature of tropical diseases in India and the diagnostic challenge they pose. Early use of rapid diagnostics is crucial for timely, targeted treatment to prevent complications like AKI.

In a cohort of 260 tropical febrile illness patients, 40.8% developed acute kidney injury (AKI), highlighting the significant renal impact of infections like dengue, scrub typhus, and leptospirosis. This AKI incidence, higher than prior South Asian studies, may reflect severe disease or referral bias. Early identification and intervention are essential to prevent progression to chronic kidney disease.

Among 106 AKI patients, 53.8% had Stage I, 35.8% Stage II, and 10.5% progressed to Stage III, indicating a typical severity gradient. KDIGO staging links higher stages to worse outcomes, with Stage III often requiring dialysis. Progression may stem from late presentation, dehydration, co-infections, or prior nephrotoxic drug use.A similar staging pattern was noted in studies by  Rajapakse et al. in Sri Lanka,¹¹ where delayed recognition of renal injury in tropical fevers led to progression beyond Stage I in one-third of cases. This reinforces the value of early biochemical testing and serial monitoring in endemic regions.

A significant association was found between dengue and AKI, with 82.1% of AKI patients testing dengue-positive versus 33.7% in the non-AKI group (P = 0.001). Dengue-related AKI arises from plasma leakage, direct viral injury, rhabdomyolysis, and acute tubular necrosis. Severe cases like dengue shock syndrome exacerbate renal damage through hypotension and cytokine-mediated endothelial injury.Mehra et al. reported an 86% dengue positivity rate among AKI patients during outbreaks, closely matching our data. Moreover, factors such as thrombocytopenia, elevated liver enzymes, and leukocytosis— frequently seen in dengue—correlate with higher AKI risk, many of which were present in your descriptive statistics.¹²

This table shows a weaker but still significant association between malaria and AKI (P = 0.01), with only 0.9% of AKI patients testing malaria-positive. While malaria, especially *Plasmodium falciparum*, can cause AKI through hemolysis and microvascular damage, its impact appears limited in this cohort. The findings suggest dengue as the primary renal aggressor, with declining malaria prevalence possibly reflecting improved urban vector control.

This table reveals a surprising inverse association between scrub typhus and AKI, with only 16.1% of scrub-positive patients developing AKI (P = 0.001). Though scrub typhus is typically a known cause of AKI due to vasculitis and interstitial nephritis, early diagnosis and timely doxycycline therapy may have limited renal complications here. Possible factors include mild disease phenotype, misclassification, or false-negative serology in scrub-negative patients. These findings highlight the need for improved diagnostics and early empiric treatment in endemic settings.

Paradoxically, enteric fever was significantly more common in patients without AKI (12.9%) than those with AKI (0.9%), indicating a statistically significant inverse relationship (P = 0.001). This suggests a lower risk of AKI among confirmed typhoid cases in this cohort. Contributing factors may include a milder disease course, timely antibiotic treatment, or sampling bias in hospitalized patients. Additionally, false-positive Widal tests may have inflated typhoid diagnoses in the non-AKI group.

Dengue positivity showed a significant increase with AKI severity—94.7% in Stage I, 57.9% in Stage II, and 100% in Stage III (P = 0.01). This gradient suggests that dengue not only contributes to AKI occurrence but also to its progression. Severe dengue forms, through mechanisms like shock, capillary leak, and rhabdomyolysis, likely drive this worsening renal injury.A study by Khalil et al¹³. showed that AKI severity in dengue correlated with thrombocytopenia, elevated hematocrit, and shock duration.

Malaria positivity across AKI stages was low—1.8% in Stage I and 0% in Stages II and III (P = 0.01), indicating a weaker link between malaria and severe AKI in this cohort. This suggests that early diagnosis and treatment may have prevented progression to advanced renal injury. The reversible nature of malaria-related AKI mechanisms, such as hemolysis and volume depletion, supports this trend. Nonetheless, clinicians should remain vigilant, as untreated *Plasmodium falciparum* can still cause severe AKI in high-risk cases.

Scrub typhus–associated AKI was more common in Stage I and II, indicating moderate severity and less frequent progression to advanced renal injury (Stage III, P = 0.01). This aligns with evidence that early antibiotic treatment often leads to recovery without dialysis, as scrub typhus typically causes reversible interstitial nephritis.

Enteric fever was rare among AKI patients (0.9%) and only seen in Stage I, with no cases in Stages II or III (P = 0.01), indicating mild AKI severity. This statistically significant distribution suggests enteric fever is linked to less severe kidney injury.

In this study, only 10.3% of AKI patients required dialysis, with no in-hospital mortality observed, highlighting effective early detection and management. These findings underscore the importance of KDIGO staging for guiding treatment and preventing progression through timely supportive care and intervention.

The study showed significant renal recovery, with serum creatinine decreasing from 2.83 to 0.99 mg/dL and urine output improving markedly by discharge, reflecting effective early intervention. These findings emphasize the value of monitoring both creatinine and urine output as key indicators of AKI prognosis and treatment response.

The study reveals a high incidence of acute kidney injury (AKI) at 40.8% among patients with tropical febrile illnesses like dengue, scrub typhus, and leptospirosis, highlighting their nephrotoxic potential. Dengue was strongly linked to AKI severity, while scrub typhus showed less severe AKI, possibly due to early treatment. Only 10.3% required dialysis, indicating most patients recovered well with conservative care. These findings emphasize the importance of early diagnosis, etiology-specific management, and standardized AKI staging for better outcomes. The study calls for ongoing research and public health efforts to reduce AKI-related morbidity in tropical regions.

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