The World Health Organization (WHO) recognized snakebite as a neglected tropical disease in 2017 and called for global action to reduce mortality and disability.[1] Snakebites affect 1.8 to 2.7 million people worldwide annually, causing an estimated 80,000 to 138,000 deaths. Envenomation occurs when venom is injected into the body through a snakebite, leading to potentially life-threatening complications with long-term physical and psychological consequences. In South Asia, around 70 of the 300 snake species are venomous, with the "big four"-common krait (Bungarus caeruleus), binocellate cobra (Naja naja), Russell’s viper (Daboia russelii), and saw-scaled viper (Echis carinatus)—being responsible for most fatalities. WHO aims to reduce snakebite-related mortality and disability by 50% before 2030. Acute kidney injury (AKI) is a frequent complication of snake envenomation, with an incidence ranging from 13% to 25%. Studies in Sri Lanka have shown that Russell’s viper and Hump-nosed viper (Hypnale hypnale) bites are the most common causes of AKI. The mechanisms of AKI include circulatory collapse, hypotension, hemolysis, disseminated intravascular coagulation, and direct nephrotoxic effects of the venom. The bite-to-needle time, referring to the interval between envenomation and antivenom administration, is a key determinant of AKI severity, as timely intervention can prevent complications. Previously, AKI was considered a transient condition, but recent studies indicate risk of long-term renal impairment, including chronic kidney disease (CKD) and end-stage renal disease (ESRD). Severe AKI requiring renal replacement therapy (RRT) is an independent predictor of poor prognosis. Therefore, renal recovery should be a therapeutic priority, and long-term follow-up is crucial to prevent CKD progression. AIMS AND OBJECTIVES This study aims to determine the incidence of acute kidney injury (AKI) following hemotoxic snake envenomation and assess its impact on patient outcomes. Hemotoxic envenomation, primarily caused by vipers, leads to systemic complications, including coagulopathy, organ dysfunction, and kidney injury. Understanding the frequency and severity of AKI in these cases will help improve early diagnosis and management strategies. A crucial objective is to determine the incidence of chronic kidney disease (CKD) in patients who develop AKI due to snake envenomation.

This study was a single-center prospective follow-up study conducted in the Department of General Medicine at Government Dharmapuri medical college and hospital, Dharmapuri year between January 2021 to march 2022. The study included 155 patients who presented with a history of hemotoxic snake envenomation and met the inclusion criteria. Inclusion Criteria and Exclusion Criteria Patients included in the study were those aged above 18 years, with confirmed hemotoxic snake envenomation and a diagnosis of acute kidney injury (AKI) based on the kidney disease. Improving Global Outcomes (KDIGO) criteria. Patients were excluded if they had neuroparalytic snake envenomation or pre-existing medical conditions such as chronic kidney disease (CKD), chronic liver disease, or coagulation disorders, as determined by medical history and previous records. Sample Size Calculation The sample size was calculated using the formula 4PQ/d2, where P represents prevalence, Q = (100 – P), and d is the allowable error (5%). Based on this calculation, a total of 155 patients with a history of hemotoxic snakebite and AKI were selected for the study. Data Analysis All collected data were entered into Microsoft Excel and analyzed using SPSS software version 17.0. Qualitative variables such as age categories, gender, time and place of snakebite, presence of bleeding manifestations, and complications at presentation were presented as frequencies and percentages, with bar diagrams and pie charts used for graphical representation. Statistical analysis was performed using the Chi-square test, and a p-value of less than 0.05 was considered statistically significant at a 95% confidence interval. Methodology To assess long-term renal outcomes, all patients were followed for three months, with serum creatinine and urine proteinuria levels monitored at the 1st and 3rd months. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI 2021 equation, and patients were classified into different stages of chronic kidney disease (CKD) according to KDIGO CKD guidelines.

Table 1: Age and Gender Distribution of Patients Age Group (Years) Frequency Percentage (%) Gender Frequency Percentage (%) 20-30 9 5.8 Male 120 77.4 30-40 35 22.6 Female 35 22.6 40-50 33 21.3 50-60 35 22.6 60-70 26 16.8 70-80 17 11.0 Total 155 100 Total 155 100 In the table 1 the majority of patients belonged to the 30-40 years (22.6%) and 50-60 years (22.6%) age groups. The male population (77.4%) was significantly higher than females (22.6%). Table 2: Time of Snake Bite and Time of Hospital Presentation Time of snakebite Frequency Percentage (%) Time of Presentation Frequency Percentage (%) Day 123 79.4 <6 hours 135 87.1 Night 32 20.6 6-12 hours 6 3.9 12-24 hours 2 1.3 >24 hours 10 6.45 Total 155 100 Total 155 100 Table 2 gives the details of patients (79.4%) were bitten during the daytime, and 87.1% reached the hospital within 6 hours, improving treatment outcomes. Table 3: Clinical Features and Laboratory Findings Parameter Frequency Percentage (%) Tourniquet Applied 105 67.75 Local Complications 149 96.12 Mild Anemia(10-12g/dL) 106 68.4 Thrombocytopenia (<1.5lakh) 77 49.7 Increased PT Time 147 94.8 INR Prolonged 147 94.83 WBCT>20 min 145 93.5 Table 3 shows: 67.75% of patients applied a tourniquet, which may delay appropriate medical intervention.96.12%had local complications, emphasizing the severity of envenomation and 49.7% had thrombocytopenia, and 94.8% had increased PT time, indicating coagulopathy. Table 4: Severity of Acute Kidney Injury (AKI) AKI Stage Frequency Percentage (%) AKI-1 69 44.5 AKI-2 39 25.2 AKI-3 47 30.3 Total 155 100 In table 4 - 44.5% had AKI-1, which is the mildest stage and 30.3% had AKI-3, indicating severe kidney injury requiring intensive care. According to table 5 16.8% required renal replacement therapy (RRT), showing a high rate of kidney dysfunction and 5.16% mortality rate, meaning most patients (94.83%) showed improvement after treatment. Table 5: Treatment Interventions and Outcomes Treatment Frequency Percentage (%) FFP Transfusion 58 37.41 PRBC Transfusion 30 19.35 Ventilator Support 10 6.5 RRT (Dialysis) 26 16.8 Surgical Intervention 22 14.2 Death 8 5.16 Improved 147 94.83 Table 6: Follow-Up after 1 and 3 Months Parameter 1Month (%) 3Months (%) Normal Serum Creatinine 93.19 85.04 Increased Serum Creatinine 2.72 4.08 Urine Proteinuria (Nil) 76.1 70.06 CKD Stages 1-2 10.88 10.20 CKD Stages 3-5 (Severe) 7.5 8.16 In table 6, most patients showed improvement, but some progressed to CKD over three months. And in the same way 8.16% developed severe CKD (Stages 3-5), requiring long-term monitoring. Table 7: Association between AKI and CKD Progression AKI Stage No CKD (%) CKD(Stage1-2) (%) Severe CKD (%) AKI-1 67.3 27.5 5.2 AKI-2 35.6 41.0 23.4 AKI-3 15.2 38.1 46.7 According to table 7 46.7% of patients with AKI-3 developed severe CKD, emphasizing the need for early intervention in AKI patients to prevent long-term kidney damage and patients with AKI-1 had the lowest progression to CKD, reinforcing the importance of early diagnosis and treatment.

The present study provides valuable insights into snake bite-induced acute kidney injury and its progression to chronic kidney disease, offering important comparisons with existing literature. Our demographic analysis revealed a clear male predominance (77.4%) with the majority of patients falling in the 30-40 years age group (22.6%). This gender distribution aligns closely with findings from Patil et al., who reported 84.2% male patients in their study. However, it presents an interesting contrast to Vikrant et al.'s research, which found a higher proportion of female victims (57.9%). The male predominance in our study likely reflects occupational exposure patterns, as most victims were from rural areas and were bitten during working hours, with 79.4% of bites occurring during daytime. A significant finding in our study was the prompt presentation to healthcare facilities, with 87.1% of patients arriving within 6 hours of the bite. This represents a marked improvement compared to the mean arrival time of 3.4 ± 3.7 days reported by Vikrant et al. This earlier presentation time may be a crucial factor contributing to the better outcomes observed in our study, particularly regarding mortality and complications. The improvement in presentation time could be attributed to better awareness and accessibility of healthcare facilities in our region. Regarding clinical manifestations, our study found an exceptionally high rate of local complications, with 96.12% of cases showing various degrees of local tissue involvement. All affected patients exhibited swelling and cellulitis, which notably differs from Vikrant et al.'s findings of only 13.6% cases with limb swelling/cellulitis. However, our observations align perfectly with Patil et al.'s study, which reported cellulitis in 100% of cases. This high rate of local complications strongly suggests a predominance of vasculotoxic envenomation in our geographical area. Of particular concern was the high rate of tourniquet application (67.75%) by patients before reaching the hospital, a practice that, while common, can potentially exacerbate local tissue damage and complicate outcomes, as documented in several studies. The laboratory parameters in our study revealed significant coagulation abnormalities, with 49.7% of cases showing thrombocytopenia, 98.7% exhibiting prolonged PT time, 93.50% showing increased WBCT, and 94.8% presenting with elevated INR. These findings indicate a higher prevalence of coagulopathy compared to Patil et al.'s study, which reported coagulation abnormalities in 36.8% of cases. This variation might be attributed to differences in snake species or severity of envenomation across different geographical regions. Table8: Comparison of acute kidney injury (AKI), need for dialysis and mortality rates indifferent Studies (10,15–19) Study AKI (%) Dialysis Received (%) Hospital Mortality among AKI Patients (%) Ali et al (2004) 17 71 25 Athappan et al (2008) 13.5 45.3 22.5 Harshavardhan et al (2013) 14.6 44.4 22.3 Dharod et al (2013) 31 55 39 Mukhopadhyay et al (2016) 44.1 33.7 29.7 Tarun K et al 21 38 6 Present study 16.8% 5.16% In terms of acute kidney injury progression, our study classified cases into three categories: AKI-1 (mild) at 44.5%, AKI-2 (moderate) at 25.2%, and AKI-3 (severe) at 30.3%. Notably, the requirement for renal replacement therapy in our study (16.8%) was substantially lower than other Indian studies, where dialysis requirements ranged from 33.7% to 71%. This reduced need for dialysis could be attributed to our better presentation times and early intervention strategies, highlighting the importance of prompt medical attention in snake bite cases. The mortality outcomes in our study were particularly encouraging, with an overall mortality rate of 5.16%, significantly lower than other studies reporting mortality rates ranging from 22.3% to 39% in AKI patients. This improved survival rate can be attributed to several factors, including earlier presentation to healthcare facilities, implementation of standardized treatment protocols, availability of renal replacement therapy, and enhanced supportive care measures. Long-term follow-up results revealed varying degrees of progression to chronic kidney disease. While 70.1% of patients maintained normal renal function (eGFR grade 1), 21.8% developed mild dysfunction (grade 2), and 8.2% progressed to moderate-severe dysfunction (grades 3-5). These findings share similarities with Waikhom et al.'s study, which reported persistent renal abnormalities in 41% of patients at 45 months follow-up. Particularly noteworthy was the progression to severe CKD in AKI-3 patients, where 46.7% developed severe CKD, emphasizing the critical importance of early intervention and consistent long-term monitoring. The three-month follow-up period may not have been sufficient to capture very long-term outcomes. Additionally, the lack of snake species identification in many cases and limited data on socioeconomic factors affecting outcomes could have impacted our analysis. Future research should focus on extending follow-up periods to better understand CKD progression, analyzing species specific treatment outcomes, investigating the role of early biomarkers in predicting AKI progression, and evaluating the impact of traditional practices on outcomes.

AKI caused by snake envenomation is a common complication. Most middle-aged men from lower socioeconomic classes are affected by this ailment. Most patients will recover with appropriate treatment including anti-snake venom, close monitoring, and timely dialysis. Out of 147 patients followed up one third patients were in different stages of CKD. Furthermore, we noted that the majority of individuals do not require dialysis and do not develop symptomatic renal morbidity. 1.38% (2 patients) had progressed to ESRD. Therefore, further prospective validation is necessary, and hospitals ought to support suitable, intense therapy that has the potential to save lives. Limitations A significant challenge we encountered was the absence of premorbid creatinine values for most patients, which made it impossible to definitively rule out the presence of prior chronic kidney disease (CKD). This limitation creates uncertainty in determining whether the observed kidney dysfunction was entirely attributable to snake envenomation or if there were pre-existing renal conditions that may have influenced the outcomes.

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