Dengue fever is a mosquito-borne viral infection caused by the dengue virus (DENV) that has emerged as a major global public health concern. The World Health Organization (WHO) estimates approximately 390 million dengue infections yearly, with about 96 million manifesting clinically.[1] The geographic distribution of dengue has expanded dramatically in recent decades, with more than half of the world's population now at risk.[2] While the majority of dengue infections remain asymptomatic or present as mild, self-limiting febrile illness, approximately 0.5-5% progress to severe forms with significant complications.[3]

Acute kidney injury (AKI) is an increasingly recognized complication of dengue infection but remains underestimated in clinical practice.[4] The reported prevalence of AKI in dengue varies widely from 0.9% to 21% depending on the study population, geographic region, and criteria used for defining AKI. Recent meta-analyses suggest a pooled prevalence of approximately 8% among hospitalized dengue patients.[5,6]

The pathophysiology of AKI in dengue is complex and multifactorial. Proposed mechanisms include direct viral invasion of renal tissue, immune-mediated glomerular injury, hemodynamic instability due to increased vascular permeability, rhabdomyolysis, hemolysis, and acute tubular necrosis.[7] Pre-existing comorbidities, particularly diabetes and hypertension, have been identified as significant risk factors for developing AKI in dengue patients.[8]

The development of AKI in dengue patients has been associated with increased morbidity, mortality, extended hospital stays, and long-term renal sequelae.[9,10] However, comprehensive studies evaluating the prevalence, risk factors, and outcomes of dengue-associated AKI in diverse clinical settings remain limited.

This study aimed to determine the prevalence of AKI among patients with dengue fever at our tertiary care center, identify clinical and laboratory predictors of AKI, and evaluate the impact of AKI on patient outcomes, particularly length of hospital stay and mortality.

Study Design and Setting

This prospective observational study was conducted at our tertiary care center over a period of 6 months from June to November 2024. The study protocol was approved by the Institutional Ethics Committee, and informed consent was obtained from all participants or their legal representatives.

Study Population

All patients aged ≥18 years admitted with confirmed dengue infection were consecutively enrolled. Dengue was confirmed by either positive NS1 antigen test and/or positive dengue IgM antibody by ELISA method. Patients with pre-existing chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73m² for >3 months), those on maintenance dialysis, and pregnant women were excluded.

Sample Size

A total of 114 patients meeting the inclusion criteria were enrolled in the study.

Data Collection

Demographic data, clinical features, comorbidities, and laboratory parameters were recorded using a standardized data collection form. All patients underwent daily clinical assessments and routine laboratory investigations including complete blood count, renal function tests, liver function tests, serum electrolytes, and coagulation profile. Additional investigations such as urine analysis and ultrasonography were performed as clinically indicated.

Definitions

1. Dengue classification was based on the 2009 WHO criteria:
• Dengue without warning signs
• Dengue with warning signs
• Severe dengue
2. AKI was defined and staged according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria:
• Stage I: Increase in serum creatinine by ≥0.3 mg/dL within 48 hours or 1.5-1.9 times baseline
• Stage II: 2.0-2.9 times increase in serum creatinine from baseline
• Stage III: ≥3.0 times increase in serum creatinine from baseline or increase to ≥4.0 mg/dL or initiation of renal replacement therapy

Statistical Analysis

Data analysis was performed using SPSS version 25.0. Continuous variables were expressed as mean ± standard deviation or median with interquartile range as appropriate. Categorical variables were expressed as frequencies and percentages. Comparisons between groups were made using Student's t-test or Mann-Whitney U test for continuous variables and Chi-square or Fisher's exact test for categorical variables. Multivariate logistic regression analysis was performed to identify independent risk factors for AKI. A p-value <0.05 was considered statistically significant.

Baseline Characteristics

A total of 114 dengue patients were included in the study. The mean age was 42.6 ± 16.3 years, with 67 (58.8%) males and 47 (41.2%) females. Comorbidities included diabetes mellitus in 23 (20.2%), hypertension in 27 (23.7%), and both in 12 (10.5%) patients. Based on the 2009 WHO classification, 41 (36.0%) had dengue without warning signs, 52 (45.6%) had dengue with warning signs, and 21 (18.4%) had severe dengue (Table 1).

TABLES AND GRAPHS:

Prevalence and staging of AKI

Among the 114 patients, AKI was diagnosed in 22 (19.3%) patients according to the KDIGO 2012 criteria. Of these, 11 (50.0%) had Stage I, 7 (31.8%) had Stage II, and 4 (18.2%) had Stage III AKI (Figure 1). The baseline characteristics of patients with and without AKI are presented in Table 1.

Table 1: Baseline Characteristics of Dengue Patients With and Without AKI

Clinical and Laboratory Features

Patients with AKI presented with more severe clinical manifestations compared to those without AKI (Table 2). Hypotension requiring inotropic support was observed in 9 (40.9%) AKI patients versus 5 (5.4%) non-AKI patients (p<0.001). Similarly, patients with AKI had higher rates of plasma leakage manifestations, bleeding complications, and organ involvement. Significant laboratory abnormalities in AKI patients included severe thrombocytopenia, elevated liver enzymes, hypoalbuminemia, and prolonged prothrombin time. The median peak serum creatinine in AKI patients was 2.3 mg/dL (IQR 1.7-3.6) compared to 0.9 mg/dL (IQR 0.7-1.1) in non-AKI patients (p<0.001).

Table 2: Clinical and Laboratory Parameters of Dengue Patients With and Without AKI

Figure 2: Risk Factors for AKI in Dengue Patients

Risk Factors for AKI

Multivariate logistic regression analysis identified several independent risk factors for developing AKI in dengue patients (Table 3 and Figure 2). These included age >60 years, pre-existing diabetes or hypertension, severe dengue, use of nephrotoxic medications, and severe thrombocytopenia (platelet count <20,000/μL).

Table 3: Multivariate Analysis of Risk Factors for AKI in Dengue Patients

Figure 3: Impact of AKI on Hospital Stay Duration in Dengue Patients

Clinical Outcomes

The development of AKI significantly impacted clinical outcomes in dengue patients (Table 4). The mean duration of hospitalization was significantly longer in patients with AKI (11.4 ± 4.3 days) compared to those without AKI (6.2 ± 2.1 days) (p<0.001). Among the 22 patients with AKI, 6 (27.3%) stayed for 5-7 days, 12 (54.5%) for 8-14 days, and 4 (18.2%) for more than 15 days (Figure 3). Three patients (13.6%) with AKI required renal replacement therapy, all of whom had Stage III AKI. The in-hospital mortality rate was significantly higher in the AKI group (13.6% vs. 1.1%, p=0.003). Among the 19 AKI survivors, 16 (84.2%) had complete recovery of renal function at discharge, while 3 (15.8%) had persistent renal dysfunction

This prospective study conducted at our tertiary care center revealed that AKI is a common complication of dengue fever, with a prevalence of 19.3% among hospitalized patients. This finding is consistent with recent systematic reviews and meta-analyses that report a  prevalence of 0.9-21%.[5] Our results are also comparable to those reported by Khalil et al., who identified AKI in 13.3% of dengue patients.[11]

The majority of AKI cases in our study were Stage I (50%), which is similar to findings reported by Patel et al. (2019) and Wang et al. (2023).[12,13] This highlights the importance of early recognition of even mild renal dysfunction in dengue patients, as it may progress to more severe forms if not promptly addressed. The relatively high proportion of Stage II (31.8%) and Stage III (18.2%) AKI in our cohort may reflect the tertiary care nature of our center, which tends to receive more severe and complicated cases.

Our study identified several risk factors for developing AKI in dengue patients, including older age, diabetes mellitus, hypertension, severe dengue manifestations, and use of nephrotoxic medications. These findings are consistent with those reported by Diptyanusa et al. (2019) and Mallhi et al. (2015), who found similar risk factors in their respective studies.[8,14] The identification of these risk factors is crucial for early risk stratification and implementation of preventive measures in high-risk patients.

The pathophysiology of AKI in dengue is multifactorial. In our study, severe thrombocytopenia, elevated liver enzymes, hypoalbuminemia, and coagulation abnormalities were significantly associated with AKI. These findings suggest that multiple mechanisms, including direct viral effects, immune-mediated injury, hemodynamic instability, and multi-organ dysfunction, contribute to the development of AKI in dengue.[7,15]

An important finding of our study was the significant impact of AKI on clinical outcomes. Patients with AKI had longer hospital stays, higher rates of ICU admission, greater need for mechanical ventilation, and increased mortality compared to those without AKI. These findings align with those reported by Surasombatpattana et al. (2021) and Eswarappa et al. (2019), who also observed poorer outcomes in dengue patients with AKI.[16,17]

The correlation between AKI severity and length of hospital stay was particularly notable in our study. More than half of AKI patients (54.5%) required hospitalization for 8-14 days, and 18.2% stayed for more than 15 days. This extended hospital stay not only increases healthcare costs but also poses additional risks for hospital-acquired complications.

Encouragingly, the majority of AKI survivors (84.2%) in our study showed complete recovery of renal function at discharge. However, 15.8% had persistent renal dysfunction, highlighting the potential for long-term renal sequelae following dengue-associated AKI. This underscores the importance of follow-up monitoring of renal function in these patients, as pointed out by Chawla et al. (2014), who described AKI and chronic kidney disease as interconnected syndromes.[18]

Limitations of the study

Our study has some limitations, including its single-center nature, relatively small sample size, and lack of long-term follow-up beyond hospital discharge. Additionally, we were unable to perform renal biopsies to determine the exact pathological mechanisms of AKI.

AKI is a common complication of dengue fever, occurring in approximately one-fifth of hospitalized patients at our tertiary care center. The development of AKI significantly extends hospital stay and increases the risk of adverse outcomes, including mortality. Risk factors for AKI include older age, pre-existing comorbidities, severe dengue manifestations, and use of nephrotoxic medications. Early recognition of dengue-associated AKI through regular monitoring of renal parameters is essential, particularly in high-risk patients. Preventive strategies should focus on optimizing fluid administration, maintaining adequate blood volume, avoiding nephrotoxic drugs, and appropriate management of comorbidities. Future multi-center studies with larger sample sizes and longer follow-up periods are needed to better understand the long-term renal outcomes of dengue-associated AKI and to develop targeted interventions for prevention and management.

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