Acute kidney injury (AKI) represents a critical complication that often arises in individuals who have suffered venomous snake bites, leading to significant morbidity and mortality worldwide. The incidence of snakebite-induced AKI varies geographically, largely influenced by the snake species involved and the availability and accessibility of medical care. Venomous snake bites can lead to a complex clinical syndrome characterized by local tissue damage, systemic coagulopathy and multiple organ dysfunction, including acute renal failure.[1] Understanding the clinical and biochemical predictors of AKI following a venomous snake bite is pivotal for the early identification and management of at-risk individuals, potentially reducing the burden of associated complication

The pathophysiology of snakebite-induced AKI is multi-factorial, involving direct nephrotoxic effects of the venom, systemic inflammation, coagulation disturbances, and the development of shock.[2] Certain venom components can directly injure renal tubular cells, while others may cause systemic effects that indirectly lead to kidney damage. Clinical predictors of AKI in the context of snake bites include the severity of envenomation, the development of systemic symptoms such as hypotension and coagulopathy, and the presence of local tissue injury. [3]

Biochemical markers have emerged as critical tools for the early detection of renal impairment. Traditional markers such as serum creatinine and the blood urea nitrogen (BUN) are widely used, but their delayed elevation following kidney injury limits their utility for early diagnosis. [4]  Novel biomarkers, including Neutrophil GelatinaseAssociated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and interleukin-18 (IL-18), have shown promise in identifying AKI at earlier stages, potentially offering a window for interventions to mitigate renal damage.[5]

The epidemiology of snakebite-induced AKI highlights the global burden of snake bites, with the highest incidences reported in South Asia, Southeast Asia, and sub-Saharan Africa. These regions coincide with the habitats of some of the most venomous snake species, such as Naja(cobras), Daboia (Russell’s viper), and Echis (saw-scaled viper), which are known for their potent nephrotoxic effects.[6] The global distribution of snakebite-induced AKI underscores the importance of localized research to identify region-specific clinical and biochemical predictors that can guide the management and prevention strategies in these high-risk areas.

AIMS AND OBJECTIVES OF THE STUDY

• To find out the incidence of acute kidney injury (AKI) in snakebite individuals.
• To find out the early predictors of acute kidney injury in snakebite patients at the time of hospital admission.

Source of data The cross-sectional observation study was conducted at the Department of General Medicine at Hassan Institute of Medical Sciences (HIMS), Hassan. Data were collected from all patients presenting with snake bites who met the inclusion and exclusion criteria over a study period of one year

Study Design:  A cross-sectional observation study design was employed to assess the clinical and biochemical predictors of acute kidney injury (AKI) in individuals with venomous snake bites.

Study Period: The study was conducted over a period of one year.

Estimation of sample size:

The sample size was estimated based on previous studies, notably the work by Dharod et al., which indicated that 30.96% of snake bite victims developed AKI. The formula used for sample size calculation was

n =Z 2 x p x q d 2

n= sample size, z=1.96, p=prevalence=30.96%=0.3096,

q=1-p=0.6904, d= precision= 5 to 20 % of p.

We have taken 20 percent of p: 20/100 x 0.3096=0.06192 n = (1.96) 2 x 0.3096 x 0.6904 (0.06192) 2

Minimum sample required is n = 215

Inclusion criteria

• Patients presenting with a history of snake bite to the Department of Medicine at HIMS Hassan, Karnataka.
• Age greater than 18 years

Exclusion criteria

• Age 18 years or below.
• Pregnant and lactating women.
• Individuals with known cases of renal dysfunction.
• Non venomous snake bite individuals.

Patients who met the inclusion criteria were recruited for the study. The aims and objectives of the study were explained to potential participants, and informed consent was obtained. Data collection was facilitated using a proforma sheet, which included information on age, sex, presenting complaints, past history, family history, socioeconomic status, education status, and occupation. The required investigations for the study were complete blood count (CBC), renal function test (RFT): urea and creatinine done by urease kinetic and kinetic alkaline picrate technique respectively, liver function test (LFT): total bilirubin, SGOT and SGPT done by diazonium salt, NADH without P5P respectively, Serum electrolytes: sodium, potassium both done by indirect ISE method, serum LDH done by lactate to pyruvate IFCC cal technique, urine routine for RBCs and proteins done by dipstick technique in the biochemistry laboratory of HIMS, Hassan.

Statistical Analysis:

Data were analyzed using descriptive statistical tools, including frequency, percentage, standard deviation, and mean calculations. For inferential statistics, appropriate statistical tests were applied based on the data type and distribution. The unpaired T-test was used for parametric data, while the Chi-square test was utilized for non-parametric data. A pvalue of less than 0.05 was considered statistically significant. Differences or associations were unlikely to have occurred by chance.

Table 1: Distribution of participants according to Bite to hospital time and AKI status

In this study among total of 215 participants AKI has highest incidence when the patient presents to hospital after 6 hours (34.74%), followed by 3-6 hours (29.47%).

Table 2: Distribution of participants according to Type of Snake and AKI status

Inthisstudymajorityofpatientspresentingwithvenomoussnakebiteidentifiedthe snake to be viper and incidence of AKI is also highest in those patients.

Table 3: Distribution of participants according to Symptoms and AKI

In this study swelling appears to be most strongly associated with AKI, with highest incidence of 84.5%, redness also has relativelyhigh association with AKI (68.3%). Other symptoms like pain abdomen, nausea and local pain seem to have a less pronounced association with AKI.

Table 4: Comparison of serum creatinine between AKI and non AKI group(n=215)

In this study serum creatinine level is significantly higher in the AKI group (2.1±0.8 mg/dL) compared to the non-AKI group (0.9± 0.3 mg/dL).

Table 5: Distribution of participants according to Stages of AKI

It was found that majority of participants with AKI studied were in stage I (80.46%), followed by stage II (14.88%) and stage III (4.65%)

In my study, out of 215 snake bite patients, 95 (44.2%) patients developed acute kidney injury. This prevalence is higher compared to the other studies from India probably due to higher number of viper snakes in our locality. Snake bites are common in the agricultural regions of Karnataka, where farming is a major source of employment.

The present study has a mean age of 50.1 years. Mean age of participants who developed AKI (55.3 ± 17.6) is slightly higher than those who did not develop AKI (45.2 ± 15.1) but not statistically significant. Mean age is comparable to Paul J Dasgupta's study (37.45 years). [7] Ptil BT's study has a significantly lower mean age (35.77 years) and a much higher standard deviation (14.92years) [8], suggesting a wider age range in their participants.

Most of the patients were found to be males in our study accounting for 53.5%. The higher incidence in males could be due to them being more involved in outdoor activities like farming and risky behavior which is similar to other studies. In a study by Usman et al male: female ratio is 1.6:1. The percentages of males were found to be 68 to 74% in various other studies. In other study by Jayakrishnan et al showed snake bite envenomation occurred more commonly in boys than in girls. Another study by Kshirsagar et al incidence were more in males (60.49%) as compared to females 54 (39.50%), this is in correlation with other studies which is similar to our study. Saborio et al found no significant gender differences.

In various studies by Kularatne SA (2003), de Silva A (1981) Sharma SK, et.al (2003), Suleman MM et.al .(1998), Ariaratnam CA (2008), Bawaskar HS et.al (2002), Kularatne SA (2002) it was noted that the male sex predominated the population who had snake bite.

In our study 22.33% patients were admitted within 1 hour of bite, 13.95% patients presented in 1-3 of snake bite, 38.6% of patients presented within 3-6 hours of snake bite, 19.07% patients presented in 6-12 hours of snake bite and 6.05% patients presented to hospital more than 12 hours after the bite. In a study by Gautam et al [9] only 3% cases reached the hospital within 1 hour of bite, 45.4% cases took 1-6 hours while 52% patients presented after 6 hours of bite which is in contrast to our study. Athappan et al, [10] found that bite to needle time more than 2 hours (OR 2.10, P = 0.001) was an independent risk factor for the development of AKI. On the contrary, Danis et al [11] observed that there was no association of bite to hospital time with development of AKI and duration of hospital stay. The bite to hospital time depends on the availability of medical facilities and the settings in which the study has been done [12]. Majority of our patients (77.7%) presented after 6 hours developed AKI which is comparable to study by conducted by Badgal A et al[13].

Majority of the snake bites in the present study were by the Russell viper similar to the findings by Athappan G et al., where majority had viper bites.  Kohli HS andSakhuja V have reported 13 to 32% incidence of Acute renal failure following Russell's viper bite in India. Russell's viper is responsible for 30–40% of the snake bites in Srilanka. In our study Russell viper bites i.e. 22 patients (44%), more commonly associated with the development of AKI.

In our study local swelling was present in 84.5%, redness in 68.3%, pain abdomen was present in 29.76% cases, local pain in 29%, blistering in 20.7%, nausea in 17.2% and neurotoxicity in 12.4%, followed by no symptoms in 8.1%. Local edema was present in all patients presenting with vasculotoxic snake bites, but cellulitis was present in only 4 (8%) patients in a study by Sahni et al. The commonest symptom in a study conducted by Lingayat et al was local pain and swelling (90.62%) and vomiting (35.94%) followed by ptosis (21.87%). In a study by Kshirsagar et al local edema was seen in all patients of vasculotoxic snake bites and cellulitis following edema developed in 23 (15.64%) patients. In another study by Gautam et al results showed 25% cases developed cellulitis.

In our study snakebite patients with neurological signs and symptoms showed no significant correlation with AKI development. This result may be either due to low prevalence of mixed type of snakebite which produces both neurological signs and haematological signs or due to pure neurotoxic snake does not produce haematological complications and AKI. In a study by Paul et al, showed presence of neurological signs was negatively correlated with development of AKI. So, if a snakebite patient is presented with only neurological features, we can hope that this patient will not suffer from AKI. 40.9 % developed cellulitis according to a study conducted by Naqvi R et al. Nearly 92.0% of them developed cellulitis in a study conducted by Harshavardhan L etal. Signs of inflammation in the present study were in majority of patients which was comparable with Athappan G and others study.

In this study patients with AKI have a higher mean Creatinine level (2.1mg/dL) compared to those without AKI (0.9mg/dL). The data suggests that serum creatinine is a reliable biomarker for differentiating between patients with or without AKI. It can be used to monitor disease progression and treatment response

In this study the mean urine output is significantly lower in individuals with AKI (0.8 ml/kg/hour) compared to those without AKI (1.5 ml/kg/hour). This difference is statistically significant with p-value of 0.0009. This data highlights the importance of monitoring urine output in patients with suspected or confirmed AKI. As reported by Das SN et al., 58.0% of the patients with reduced GFR among the cases of AKI following snake bite, had >50.0% reduction in GFR.

In our study the individuals with AKI are more likely to have proteinuria compared to those without AKI. Similarly, in a study by Patil TB et al. it was noted that 100% of cases who develop renal dysfunction had proteinuria showing that proteinuria can be a predictor of organ dysfunction in snake bite.

In our study 19.5% patients received <10 vials ASV, 33.3% patients received 11- 20 ASV and 47.2% patients received 21-30 vials of ASV and patients who received lesser ASV were at high risk for development of AKI. In a study by Paul et al, development of AKI was independently associated with 20min WBCT (P value = 0.029), dark or brown colour urine (P value = 0.000; CI 95%), and time in between snakebite and administration of anti-snake venom and AKI was not significantly correlated with local swelling, bleeding from bite site, and amount of ASV given which is in contrast to our study. In another study by Yeung et al reported that patients received initial small doses of Anti-venom were associated with serious consequences. Pinho et al quotes that delay in ASV administration is a very important factor associated with the development of AKI and mortality.

Mean length of hospital stay in our study was 12.5 days as compared to 5-12 d reported in other studies like Chugh KS et al, Athappan G et al, Danis R et al, Harshavardhan L et al,Albuquerque PL et al, Krishnamurthy S et al and Li W et al. AKI is a strong predictor of mortality among the in-hospital patients with snake bite as seen in study by David S et al and Kalantri S et al[14].

In this study it was found that majority of patients (86.31%) improved after developing AKI, in contrast to study by Priyamvada PS et al, the mortality of patients with haemotoxic envenomation was 21.5%. The mortality was considerably higher in patients with Kidney Disease: Improving Global Outcomes (KDIGO) Stage 3 AKI [relative risk (RR) 4.45 (95% CI 1.14–17.42)] and those who met KDIGO urine output criteria [RR 20.45 (95% CI 2.84–147.23)] [15] .

Adverse renal outcomes (eGFR 0.3) occurred in 13.68% of AKI patients, in contrast to study done by Manoj K et al. [16]

In our study AKI was found in 44.2% cases, and 86.31% cases recovered. 30 patients with acute kidney injury needed haemodialysis and all patients recovered as reported by Shyna et al which are similar to our study. The mortality of snake bite induced acute renal failure is found to be 4% in Imtiaz et al [17-18] study.

Clinical variables like signs of inflammation, lapse of time of >12 hours in presenting to the hospital, mean serum creatinine and mean blood urea elevations with significant p-value is comparable with Athappan G and others study.

Snake bites are still a common medical emergency encountered, especially in rural areas. Timely treatment is the mainstay for reduction of morbidity and mortality. Recognition of predictors is essential for clinical management and early referral which could lead to a significant decrease in morbidity and mortality.

The study demonstrates that the incidence of AKI is 44.2% in Snake bite patients. Timely and judicious administration of an adequate dose of anti-venom may reduce the development of AKI.

Based on the present study, it was found out that in venomous snake bite patients, prolonged bite to hospital time, viper bites, local swelling, serum LDH, total bilirubin, AST, ALT, PT, aPTT, INR, proteinuria, hematuria and oliguria are early predictors of development of acute kidney injury.

Haematotoxicity, occurrence of cellulitis, bleeding manifestations, requirement of dialysis, elevated serum creatinine levels and reduced estimated GFR levels were significantly associated with bite to needle time of > 6 hours. The fact that snake venom responsible for most of the complications must be neutralized as early as possible is well established.

ASV should be a part of the primary health care package in areas where snake bites are common thereby referral to higher centers can be minimized. To prevent getting bitten by snakes, educating the public on making their houses snake proof and using a torch when going out during night time will help.

In conclusion, this study emphasizes the significant burden of AKI in patients with venomous snake bite and the need for heightened awareness, timely diagnosis and appropriate management to improve patient outcomes. The findings lay the foundation for further research and the development of evidence- based guidelines for the diagnosis and treatment of AKI in patients with venomous snake bite.

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