|Year : 2018 | Volume
| Issue : 1 | Page : 14-17
Snake envenomation-induced acute interstitial nephritis
Thanigachalam Dineshkumar, Jeyachandran Dhanapriya, Subramaniam Murugananth, Dhanikachalam Surendar, Ramanathan Sakthirajan, Dhanasekaran Rajasekar, T Balasubramaniyan, Natarajan Gopalakrishnan
Department of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
|Date of Web Publication||26-Mar-2018|
Dr. Jeyachandran Dhanapriya
Department of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai - 600 003, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background and Objectives: Acute kidney injury (AKI) is one of the major complications of snake envenomation, especially in the developing countries. The most common renal histology in snakebite-induced AKI is acute tubular injury (ATI), but acute interstitial nephritis (AIN) is rarely reported. Materials and Methods: We did a prospective observational study between January 2012 and May 2017 to analyze the demographic, clinical, and laboratory data, response to treatment, and outcome of patients with snakebite-induced AIN. Results: About twenty patients were included in the study with mean follow-up of 24 ± 6 months. Of them, 6 (30%) were males. Mean age was 50.9 ± 22.1 years. All the patients received anti-snake venom. AKI developed after a mean duration of 24.1 ± 11.2 h and 15 patients were oliguric. Cellulitis was seen in 65% of patients, anemia in 65%, leukocytosis and thrombocytopenia in 40%, and coagulopathy in 80%. Mean peak serum creatinine was 7.8 ± 3.2 mg/dL. Peripheral eosinophilia was seen in 7 (35%) patients. All the patients were managed with hemodialysis and all except one received oral steroids. Six patients (30%) progressed to chronic kidney disease (CKD) with mean follow-up creatinine of 1.49 ± 0.8 mg/dL. Conclusion: It is prudent to do renal biopsy in patients with snakebite-induced AKI when there is a suspicion of pathology other than ATI. Identification and treatment of AIN with steroid will avoid progression to CKD which has an impact on growing health burden in tropical countries.
Keywords: Acute interstitial nephritis, acute kidney injury, renal biopsy, snakebite
|How to cite this article:|
Dineshkumar T, Dhanapriya J, Murugananth S, Surendar D, Sakthirajan R, Rajasekar D, Balasubramaniyan T, Gopalakrishnan N. Snake envenomation-induced acute interstitial nephritis. J Integr Nephrol Androl 2018;5:14-7
|How to cite this URL:|
Dineshkumar T, Dhanapriya J, Murugananth S, Surendar D, Sakthirajan R, Rajasekar D, Balasubramaniyan T, Gopalakrishnan N. Snake envenomation-induced acute interstitial nephritis. J Integr Nephrol Androl [serial online] 2018 [cited 2018 Jun 17];5:14-7. Available from: http://www.journal-ina.com/text.asp?2018/5/1/14/228494
| Introduction|| |
Snake envenomation continues to be a major health burden in tropical countries including India. These patients are being managed at all levels of health care, and those requiring renal replacement therapy are being referred to nephrology care units. The usual pathology in kidney biopsy is acute tubular injury (ATI) and cortical necrosis. Acute interstitial nephritis (AIN) is rarely reported, and its response to treatment and prognosis remains elusive. Here, we report a cohort of eighteen patients with snakebite-induced AIN, their presentation, treatment, and outcome.
| Materials and Methods|| |
We conducted a prospective observational study in adult patients (13–70 years) admitted to the Institute of Nephrology, Madras Medical College with acute kidney injury (AKI) after snakebite from January 2012 to May 2017. Renal biopsy showing AIN was included in the study. Patients with preexisting kidney disease and unknown bite were excluded. Snake species was identified using charts or visualization by the treating physician. If snake species was not identified snake species, it is documented as unknown. Clinical history such as onset of local envenomation, neurological symptoms, oliguria, volume overload, hematuria, physical and systemic examination, and laboratory data were noted. The probable drugs causing AIN such as analgesics and native medications were excluded, and none of the patients had hypersensitivity to anti-snake venom (ASV). Patients were initiated on hemodialysis (HD) using temporary nontunneled catheters. Kidney biopsy was performed if renal failure was persistent for more than 2–3 weeks or earlier if persistent anuria for more than a week or suspicion of pathology other than ATI like fragmented RBCs in peripheral smear. Evidence of glomerular injury, tubular injury, and infiltration of lymphocytes and eosinophils in the interstitium were sought for and noted. Renal biopsy showing marked interstitial infiltration of inflammatory cells only was included, and milder forms were excluded from the study. Steroid protocol included oral prednisolone 0.5 mg/kg/day for 2 weeks and tapered over 1 month. Follow-up renal function test monitoring was done at regular intervals. Chronic kidney disease (CKD) was defined as serum creatinine of >1.5 mg/dL at the end of 3 months.
| Results|| |
Total number of patients with snakebite-induced AKI over 5 years was 196, out of which, 85 biopsies were done. Twenty (23.5%) patients who underwent biopsy had AIN. The mean follow-up was 24 ± 6 months. Of them, 6 (30%) were males. Mean age was 50.9 ± 22.1 years. All the patients received ASV with mean lag time of 14.1 ± 4.1 h. Coronary artery disease was present in one patient and type 2 diabetes was in two patients. Russell's viper (5), saw-scaled viper (4), and krait (1) were the snake species identified, and species was not identified in ten patients.
The clinical features and laboratory investigation are given in [Table 1]. AKI developed after a mean duration of 24.1 ± 11.2 h. Oliguria was the most common renal presenting symptom (15 patients). Serum immunoglobulin E (IgE) was done only in seven patients which was elevated. All patients required HD. Number of HD sessions ranges from 3 to 13. Renal biopsy in all the patients showed marked infiltration of eosinophils and lymphocytes along with tubular injury [Figure 1]. Immunofluorescence was negative for all the stains. Treatment and outcome of individual patients are given in [Table 2].
|Figure 1: Renal biopsy showing interstitial infiltration of eosinophils and lymphocytes|
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One patient had not received steroids since biopsy was done after 40 days. The mean serum creatinine at follow-up of 24 months was 1.49 ± 0.8 mg/dL. Six patients progressed to CKD at mean follow-up.
| Discussion|| |
The estimated number of deaths due to snakebite was 14,000 in South Asia. Snakebite-induced AKI accounts for about 1.2% in Thailand, 3% in India, and 70% in Myanmar. The important snake species in India are the Indian cobra (Naja naja), the Russell's viper (Daboia russelii), the saw-scaled viper (Echis carinatus), and the common krait (Bungarus caeruleus). AKI most commonly occurs after hematotoxic viperidae bite. The onset of renal failure varies from a few hours to as late as 96 h after the bite. In our study, Russell's viper was the most common species causing envenomation, and species was not identified in ten patients. Females were commonly affected (70%). In a study including 57 patients of dialysis-requiring AKI due to snakebite, cellulitis was seen in 100% of patients, anemia in 54.3%, leukocytosis in 61.4%, thrombocytopenia in 42.1%, and coagulopathy in 36.8%, while in our study, it was seen in 65%, 65%, 40%, 40%, and 80%, respectively. The mortality was 15.5% and the risk factors were the presence of coagulopathy and uremic encephalopathy. Snake venom contains more than hundred different proteins such as metalloproteinase hemorrhagins, phospholipase A2, procoagulant enzymes, hyaluronidase, nonenzymatic polypeptide toxins, and some nontoxic proteins. The mechanisms of renal injury include direct nephrotoxicity, hemodynamic alterations, immunologic reactions, and vasoactive mediator release. Most common renal pathology following snake envenomation is ATI and cortical necrosis followed by glomerular involvement, fibrinoid necrosis and occlusive thrombosis, acute diffuse interstitial nephritis, and thrombotic microangiopathy.,
Literature regarding snakebite-induced AIN is sparse. It was first reported by Sant and Purandare in 1972, later Sitprija et al. in 1982 observed AIN in three patients., Others include few case reports and two case series each including five patients.,,,,, In both the series, all patients had severe envenomation at presentation and had prolonged renal failure. All the previous reports of AIN induced by snakebite were due to hemotoxic Russell's viper. In our series, one was due to krait bite which have never been reported previously. The possible mechanism of AIN is due to immunogenic effects of snake venom resulting in the development of the interstitial inflammation by elaboration of various cytokines, mediators and adhesion molecules and tubular injury leading to neoantigen release resulting in interstitial inflammation as snake venom toxins could have shared homology to template-based modeling., In our study, peripheral eosinophilia was evident in 7 (35%) patients and serum IgE levels was done only in seven patients due to logistic reasons but was elevated in all. We were not able to estimate eosinophiluria due to nonavailability.
In one study of AKI after snakebite, the mean age was 50 years and 72% were men. At 1 year, 37% developed CKD and 63% had recovered. Renal histology of six CKD snakebite patients showed predominant glomerular sclerosis and interstitial nephritis. AIN accounted for 5.7% of snakebite-related AKI in a series and mixed infiltrate composed of predominantly lymphocytes, with variable proportions of other cells including eosinophils neutrophils and plasma cells were seen in renal biopsy.
Though there are no guidelines regarding use of steroids in snakebite-induced AIN, all but one of our patients received oral prednisolone 0.5/kg/day for 2 weeks tapered over 1 month as there were some evidence regarding use of steroid in drug-induced AIN., At mean follow-up of 24 ± 6 months, six patients (30%) progressed to CKD. The response rate to steroids was 80% in one series. Golay et al. reported a response rate of 20%, with remaining patients progressing to CKD/end-stage renal disease. The overall outcome in this group was worse than those who did not have AIN.
| Conclusion|| |
We emphasize on the prompt identification by early biopsy and treatment of AIN. It assumes great significance since treatment with steroids can avoid/retard the progression to CKD. The role of peripheral eosinophilia and serum IgE levels in early prediction for snakebite-induced AIN has to be validated in larger number of patients.
We thank Dr. Anila Abraham Kurien MD, Director, RENOPATH, Chennai for her help in evaluation of renal biopsy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]