ACUTE KIDNEY INJURY FOLLOWING HUMP - NOSED PIT VIPER ( Hypnale hypnale ) ENVENOMATION : A PROSPECTIVE STUDY FROM A TERTIARY SOUTH INDIAN CENTRE

Snakebite continues to be an important, yet often neglected ,tropical health problem in South Asia .The hump-nosed pit viper (HNPV), a venomous species endemic to Sri Lanka and the Western Ghats of India, comprises three species—Hypnale hypnale, H. zara, and H. nepa—of which only H. hypnale is found in India. Traditionally regarded as a  "minor" venomous snake  causing only localized envenomation, H. hypnale is now increasingly being  recognized as a cause of severe systemic toxicity and mortality. Acute kidney injury (AKI) following Hypnale hypnale (HNPV) envenomation is likely multifactorial.1 Direct nephrotoxicity from venom metalloproteinases and phospholipases can induce tubular and endothelial injury as reflected by early tubular biomarker elevations.2 Microvascular thrombosis and thrombotic microangiopathy (TMA) represent another important mechanism—patients with venom-induced consumption coagulopathy (VICC) may develop RBC fragmentation-type TMA characterized by thrombocytopenia, microangiopathic hemolytic anemia, and renal microthrombi leading to cortical ischemia and acute tubular injury.3 Additional contributors include pigment nephropathy from hemolysis or, less commonly, myoglobinuria causing tubular obstruction and oxidative damage , and secondary ischemic injury due to hypotension or shock, which, though less frequent than in elapid or large viper bites, may occur in severe cases.

But Indian data  describing the clinical pattern and outcomes  in HNPV envenomation remain limited.There is no specific antivenom effective against H. hypnale, leaving treatment largely supportive. This study aimed to evaluate the clinical features, renal manifestations, and short-term outcomes of patients with confirmed HNPV bites managed at our tertiary care hospital in Kerala.

Aims and Objectives

1.    To determine the incidence and severity of acute kidney injury (AKI) in patients with confirmed Hypnale hypnale envenomation.

2.    To characterize the clinical features, laboratory findings, and complications associated with HNPV bites.

3.    To identify predictors of AKI development in this population.

4.    To evaluate renal recovery and short-term outcomes, including the need for dialysis and mortality.

Materials and Methods

A prospective observational study was conducted in the Departments of Nephrology and Critical Care Medicine at Mar Sleeva Medicity, Kerala, India. The study spanned three years, from January 2022 to December 2024, following approval from the institutional ethics committee.

Adults aged ≥18 years with a definite or clinically confirmed Hypnale hypnale bite presenting within 72 hours were included. Patients with pre-existing chronic kidney disease (stage ≥3) or co-envenomation by other snake species were excluded.

Data were collected on demographics, time to presentation, clinical manifestations (local and systemic), and laboratory parameters. Acute kidney injury (AKI) was classified according to the KDIGO 2021 criteria. All patients received appropriate supportive management, and dialysis was initiated when clinically indicated. Follow-up evaluations were performed at discharge, and subsequently at 1 and 3 months.

Statistical analyses were performed using SPSS version 26.0, with appropriate tests applied; a p-value <0.05 was considered statistically significant.

A total of 52 patients with confirmed Hypnale hypnale bites were included in the study. The cohort had a mean age of 51.2 ± 12.7 years, with a male-to-female ratio of 2.2:1. The majority of bites occurred on the lower limbs, predominantly during agricultural activities. Systemic manifestations were common, including vomiting (38%), dark-colored urine suggestive of hemoglobinuria or myoglobinuria (16%), bleeding tendencies (21%), and oliguria (14%).

Acute kidney injury (AKI) developed in 28% of patients (n=15), with distribution across KDIGO stages as follows: Stage 1 in 5 patients, Stage 2 in 3, and Stage 3 in 7; six patients required renal replacement therapy. Multivariable analysis identified delayed presentation (>6 hours), coagulopathy, thrombocytopenia and proteinuria as independent predictors of AKI (p<0.05). Severity of local reaction has no correlation with the development of AKI.

All patients survived, except for one who succumbed to disseminated intravascular coagulation (DIC).At discharge, 80% achieved complete renal recovery, 10% had partial recovery, and 10% demonstrated persistent renal impairment. On follow-up at three months, two patients exhibited mild chronic kidney 

Discussion

In our prospective cohort of 52 confirmed Hypnale hypnale bites, AKI occurred in 28% (n=15), including seven KDIGO stage 3 cases and six requiring dialysis. This incidence exceeds earlier reports describing AKI as infrequent but aligns with recent regional data highlighting severe renal involvement as a significant outcome in referred cases. After an extensive literature review, no previous reports were found on HNPV-induced  dialysis requiring AKI .Of the seven patients requiring  dialysis, four experienced a prolonged renal recovery time of  more than four weeks, while two had persistent renal impairment. Consistent with previous studies, delayed presentation (>6 hours), coagulopathy, thrombocytopenia and proteinuria independently predicted AKI in our multivariable analysis.

Multiple studies (including ours) show delayed presentation correlates with worse renal outcomes. Early measurement of creatinine and simple bedside tests (urine output, dark urine) plus coagulation studies should be routine for all suspected HNPV bites. A creatinine measured within 4 hours post-bite has been reported as a useful early predictor of subsequent AKI in other cohorts.

Cross-neutralization studies and clinical reports consistently show that currently available polyvalent antivenoms do not reliably neutralize HNPV venom; therefore, supportive care (including timely dialysis) remains the mainstay. This gap underscores the urgent need for regionally relevant antivenom development or improved paraspecific formulations.

For patients who develop TMA after envenomation, case reports and small series suggest therapeutic plasma exchange may improve hematological parameters (platelets, MAHA) and, in some series, renal function if instituted early; evidence is limited and mostly observational, so consideration should be individualized and balanced against resource availability and patient stability. In our cohort, there is no single TMA suspected case reported.

 The use of fresh frozen plasma or clotting factor replacement in venom-induced consumption coagulopathy remains controversial. In the absence of antivenom, such therapy may transiently worsen the coagulopathy. But we administered Fresh Frozen Plasma and cryoprecipitate  to all the dialysis requiring patients and observed some improvement, Therefore, supportive transfusion should be guided by clinical evidence of bleeding and relevant laboratory parameters.

All patients in our cohort survived except one. At discharge, 80% showed complete renal recovery, 10% had partial recovery, and the remaining 10% had persistent renal impairment, indicating that while most renal dysfunction was reversible, a subset experienced lasting sequelae. . Long-term follow-up beyond 3 months is needed to establish chronic kidney disease risk following HNPV-associated AKI.

Strengths and limitations

Strengths of our study include prospective data collection, confirmed HNPV envenomation (by sending images to herpetologist), and systematic follow-up to 3 months. Limitations include single-center design, modest sample size (limiting precision for risk estimates), and lack of renal histopathology. Biomarkers (e.g., urinary NGAL, cystatin C) were not systematically obtained for all patients — future studies should incorporate these for earlier AKI detection and mechanistic insight. 

HNPV envenomation is an emerging cause of tropical AKI. This study is one of the earliest reports on dialysis requirement  .

Clinicians in HNPV-endemic areas should closely monitor renal function and seek early nephrology referral .

 Region-specific antivenom research and cross-neutralization studies are urgently needed.

 Multicentre registries and trials should clarify TMA incidence, evaluate plasma exchange efficacy, and assess long-term renal outcomes.

Public health initiatives to reduce treatment delays may lessen AKI severity and frequency.