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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2012  |  Volume : 23  |  Issue : 6  |  Page : 1262-1267
Acute interstitial nephritis in patients with viperine snake bite: Single center experience of a rare presentation

1 Department of Nephrology, Institute of Postgraduate Medical Education and Research, Kolkata, India
2 Consultant in Nephropathology, The Madras Medical Mission, Chennai, India

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Date of Web Publication17-Nov-2012


Acute renal failure following vasculotoxic viperine snake bites is very common in South Asia. Acute tubular necrosis and acute cortical necrosis are the common findings, with acute interstitial nephritis (AIN) being a rare presentation. We conducted renal biopsies in all patients who were admitted in our institute with viperine snake bite-related acute kidney injury (AKI) and who did not improve after three weeks of supportive care. Patients who had findings of AIN on renal histology were included for this study. Of a total of 42 patients, there were five patients (11.9%) with AIN. Our series of five patients is the largest series of this rare presentation in the literature. All of these five patients had features of severe envenomation, severe AKI network stage of AKI and very high antivenom requirements. They had a very prolonged stay in the hospital, and four of the five patients developed chronic kidney disease on follow-up. The overall outcome in this group was worse as compared with those who did not have AIN. AIN following viperine snake bites is not a very rare presentation. The reason for the development of this pathology is unclear, but direct venom-related effects are possible. This presentation portends a poor overall long-term prognosis as demonstrated in our case series.

How to cite this article:
Golay V, Roychowdhary A, Pandey R, Singh A, Pasari A, Abraham A. Acute interstitial nephritis in patients with viperine snake bite: Single center experience of a rare presentation. Saudi J Kidney Dis Transpl 2012;23:1262-7

How to cite this URL:
Golay V, Roychowdhary A, Pandey R, Singh A, Pasari A, Abraham A. Acute interstitial nephritis in patients with viperine snake bite: Single center experience of a rare presentation. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2022 Aug 17];23:1262-7. Available from: https://www.sjkdt.org/text.asp?2012/23/6/1262/103573

   Introduction Top

Venomous snakes are found throughout the world, and the incidence of snake bite and related mortality are encountered all over the globe. An incidence of renal involvement with snakebite envenomation of 1.4-28% has been reported in various series. The most common species associated with renal lesions are Russell's viper, Echis carinatus, puff adder and sea snake. In India, the incidence of acute kidney injury (AKI) is 13-32% following Echis carinatus or Russell's viper bite. [1] Renal failure averages two to three weeks in duration. Prolonged renal failure with oligo-anuria is observed in patients with cortical necrosis or acute tubular necrosis (ATN) associated with either interstitial nephritis or extracapillary glomerulonephritis. Acute glomerulonephritis in viper bite can cause mild renal failure. [2]

We present a series of five patients who underwent renal biopsies and had a histological finding of acute interstitial nephritis (AIN).

   Materials and Methods Top

We included cases from a cohort of 42 patients admitted in the Nephrology Department of the Institute of Postgraduate Medical Education and Research, Kolkata, from January to December 2011 with AKI following snake bite envenomation. AKI was diagnosed as per the AKI network criteria. [3] The severity of the snake bite was assessed by a scoring system that included local effects, systemic features and coagulation abnormalities, taking the most severe of the three as the severity grade. [4] All these patients received standard care for snake bite envenomation, including anti-snake venom (ASV) and renal replacement therapies. [5] Severity of the renal failure on admission was assessed according to the Stuivenberg Hospital Acute Renal Failure (SHARF) II and Sequential Organ Failure Assessment (SOFA) scoring systems at the time of admission and 48 h later. [6],[7] Patients who remained oliguric or whose serum creatinine did not satisfactorily decrease (defined for this study as a failure of serum creatinine to decrease to less than 50% of the peak value attained) at the end of three weeks underwent a renal biopsy after an informed consent. The renal biopsy sample was examined with light and immunofluorescence microscopy.

   Results Top

We identified five patients of 42 (11.9%) of the originally screened patients with renal biopsy findings of AIN [Figure 1]. The clinical, laboratory and treatment details of all the patients were recorded and are represented in [Table 1] and [Table 2]. None of the patients had complained of bilateral flank pains and an ultrasound of KUB showed normal-sized kidneys with increased echo-texture.
Figure 1: Renal biopsies (A, B, C, D of case 3, 4, 1 and 2, respectively) showing marked interstitial inflammatory infiltrates consisting of lymphocytes and occasional eosinophils (black arrow, A). The interstitium is edematous (A) and the glomeruli are normal (C and D). There is also evidence of tubular damage in the form of loss of the brush border and denudation with cellular debris in the tubular lumen (white arrow, D). Hematoxylin and eosin ×400 (A, B), ×100 (C, D).

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Table 1: Clinical characteristics of the five cases.

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Table 2: Laboratory, histology and other associated characteristics.

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All our five patients were adult agricultural workers who were bit while working in the fields. Russell's viper was the snake species that was identified by the patients and bystanders in all the five cases. All the five patients had severe grade of snake bite envenomation, and four of the patients (except case 2) had Stage 3 AKI on admission. The patients had a relatively severe degree of hypercatabolic renal failure; hypercatabolism was defined as a rise in serum creatinine of ≥1.5 mg/dL/24 h or a rise in serum urea of ≥30 mg/dL/24 h. [8] All the five patients had very high SHARF II and SOFA scores at 0 and 48 h. There was also a worsening of the SOFA score, i.e. ∆SOFA 48- 0, which is a predictor of poor overall outcomes. All the five patients received very high doses of ASV that required repetition due to the severity of the disease. ASV was administered initially in the prescribed test dose, followed by the complete dosage, if there was no hypersensitivity reaction; none of the patients demonstrated any hypersensitivity reaction to ASV. The eosinophil count in the CBC, which was done once every three days during hospitalization, remained within normal limits.

The baseline and the clinical progression had significant bearing on the overall outcome. Case 2 had a complete recovery of renal function at the last follow-up (11 months). She had a relatively less-severe grade of envenomation and had an earlier onset of good urine output and improvement of renal function and, thus, a shorter duration of hospital admission. Even though she had high AKI severity scores with significant coagulopathy, she was hemodynamically more stable than the other cases who all had hypotension on admission. All the cases except case 2 received a course of prednisolone at a dose of 1 mg/kg/day with tapering over one month, but the overall outcome did not improve in any of the cases, with two of them ending as chronic kidney disease (CKD) Stage 4 (cases 1 and 5), one as CKD Stage 3 (case 4) and one of them became dialysis dependent (case 3).

Renal biopsies showed extensive interstitial inflammation in all the five cases, with predominantly lymphocytic infiltration in all of them except case 4, where eosinophils were predominant along with lymphocytes. All the cases (except case 1) had eosinophils as a component of the inflammatory infiltrate. Cases 2-5 had some evidence of secondary tubular injury along with the AIN; case 2 had evidence of tubular necrosis as well. The glomeruli and the blood vessels were normal and there was no evidence of immune deposits on immunofluorescence microscopy.

Of the remaining 37 patients, 10 (27%) patients died within three weeks, 19 (52%) recovered within two to three weeks of the snake bite and did not undergo renal biopsy and all of them had a good long-term outcome with complete recovery of their renal function and eight (21%) patients had a renal biopsy finding of ATN. These eight patients also had evidence of severe envenomation, but had better AKI scores and had an earlier recovery of renal function. Two of the eight (25%) patients with ATN developed CKD (3 and 4 in each) on follow-up.

   Discussion Top

Renal involvement following snake bite en-venomation has been reported with many snake species, but the most severe of these, i.e. acute renal failure, is seen predominantly with the bite of the vipers. In India, this is usually seen with Russell's viper and the Saw-scaled viper bites that are the most widespread viper species in India. [9] The frequency of snake bite as a cause of acute renal failure has been variably reported as 1.2% in Thailand, 3% in India and as high as 40% in Myanmar. [10],[11] Snake venoms can cause cellular injury through enzymes, polypeptide toxins, cytokines and mediators. Snakes that cause renal failure are either myotoxic or hemotoxic snakes causing rhabdomyolysis, intravascular hemolysis, disseminated intravascular coagulation (DIC) or hemorrhage. [12]

Renal failure occurs a few hours to several hours after the bite, with a rapid rise of blood urea nitrogen and serum creatinine. Non-oliguric renal failure is not uncommon, and averages two to three weeks in duration. The renal histology mainly consists of ATN and AIN, while glomerular changes are rare.

In one of the early reports of snake bite from India, Chugh et al described renal histology in 44 patients of snake-bite related ARF. Thirty-two of these 44 patients (73%) had predominant changes of ATN. Forty-six patients (66%) recovered and four patients (6%) had persistent mild to moderate renal insufficiency. [11] Pal et al from Kolkata reported histology of the kidneys from 20 lethal cases of snake biterelated ARF. Histopathological changes revealed ATN and cortical necrosis as the predominant finding along with glomerular changes in a few cases. [12]

Degeneration, necrosis and regeneration of tubular epithelial cells have been observed in renal failure following the bite by either hematotoxic or myotoxic snakes, [11],[14],[12],[13],[14],[15],[16] in addition to interstitial edema and cellular infiltration, which consist of lymphocytes, plasma cells and mononuclear phagocytic cells. However, diffuse AIN out of proportion to tubular degeneration has been rarely observed in Russell's viper bite.

Although AIN accounts for 5-15% of all cases of ARF, [17] only four single case reports of AIN following snake bite have been reported earlier. Sant and Purandare reported an autopsy study of a patient with hemorrhagic interstitial nephritis. [18] Sitprija et al and Indraprasit et al from Thailand reported one case each of AIN following Russell viper bite. [19],[20] The fourth case was reported by Gundappa et al. from India following a viperine bite. [21] Our series of five cases is thus the largest collection of cases reported so far in the literature to the best of our knowledge. All the three cases reported previously were patients who were oliguric with prolonged course of renal failure, which prompted the clinicians to consider diagnoses other than ATN. The histopathology of the two cases reported from Thailand and the one from India were similar in the presence of severe interstitial inflammation, which comprised of lymphomononuclear cells. However, the latter was distinct in the presence of eosinophils in the interstitial infiltrate. The five cases in our series marked a similar clinical course of prolonged duration of renal failure with prolonged oliguric phase and presence of eosinophils in the interstitial infiltrate in four cases. The incidence of AIN was 11.9% among all cases of renal failure in our institute, which gives an interesting observation that AIN following snake bite is not such a rare entity as described previously.

Although many factors can contribute to the development of AIN, snake venom has been postulated to directly result in the development of the interstitial inflammation via various cytokines, mediators and adhesion molecules. [12] The presence of eosinophils in the interstitium in four of the five cases in our series may suggest some contribution by drugs that were given in the management of these cases (proton pump inhibitors and penicillin antibiotics, which were prescribed in all cases). Nevertheless, the role of direct nephrotoxicity of snake venom is still not clear, but hypersensitivity to venomous or antivenom protein has been occasionally found to cause acute renal failure. [11] An interesting observation in our series was that all the cases received a very high dose of ASV due to the severe envenomation. The contribution of the anti-venom to the development of the AIN needs to be determined as there is no significant data to implicate this relationship. The histological finding of AIN correlated with poor prognosis in our study as four of the five patients developed CKD.

   References Top

1.Chugh KS, Pal Y, Chakravarty RN, et al. Acute renal failure following poisonous snake bite. Am J Kidney Dis 1984;4:30-8.  Back to cited text no. 1
2.Sitprija V, Boonpucknavig V. Glomerular changes in tropical viper bite in man. Toxicon 1983; 21(Suppl 3):401-3.  Back to cited text no. 2
3.Mehta RL, Kellum JA, Shah VS. Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.  Back to cited text no. 3
4.Gold BS, Dart RC, Barish RA. Bites of venomous snakes. N Engl J Med 2002;347:347-56.  Back to cited text no. 4
5.Warrell DA. Guidelines for management of snake bites. WHO 2010.  Back to cited text no. 5
6.Lins RL, Elseviers MM, Daelemans R, et al. Reevaluation and modification of the Stuivenberg Hospital Acute Renal Failure (SHARF) scoring system for the prognosis of acute renal failure: An independent multicentre, prospective study. Nephrol Dial Transplant 2004;19: 2282-8.  Back to cited text no. 6
7.Ferreria FL, Bota DP, Bross A, Melot C, Vincent JL. Serial Evaluation of the SOFA Score to Predict Outcome in Critically Ill Patients. JAMA 2001;286:1754-8.  Back to cited text no. 7
8.Lee VWS, Harris D, Andersen RJ, Schrier RW. Acute Renal Failure. In Schrier RW, ed; Disease of the Kidney & Urinary Tract, 8 th ed. Philadelphia, PA: Lippincott Williams & Wlkins; 2007. p. 986-1034.  Back to cited text no. 8
9.Whitaker R. Common Indian Snakes. A field guide. New Delhi: Macmillan; 1978.  Back to cited text no. 9
10.Chugh KS. Etiopathogenesis of acute renal failure in the tropics. Ann Natl Acad Med Sci 1987;23:88-99.  Back to cited text no. 10
11.Chugh KS. Snake-bite-induced acute renal failure in India. Kidney Int 1989;35:891-907.  Back to cited text no. 11
12.Sitprija V. Snake bite Nephropathy. Nephrol 2006;11:442-8.  Back to cited text no. 12
13.Pal M, Maiti AK, Roychowdhury UB, Basak S, Sukul B. Renal pathological changes in poisonous snake bite. J Indian Acad Forens Med 2010;32(1):19-21.  Back to cited text no. 13
14.Sitprija V, Boonpucknavig V. The kidney in tropical snake bite. Clin Nephrol 1977;8:377- 83.  Back to cited text no. 14
15.Shastry JC, Date A, Carman RH, Johny KV. Renal failure following snake bite. Am J Trop Med Hyg 1977;26:1032-8.  Back to cited text no. 15
16.Aung W, Kyaw KP, Hla B, et al. Renal involvement in Russell's viper bite patients without disseminated intravascular coagulation. Trans R Soc Trop Med Hyg 1998;92:322-4.  Back to cited text no. 16
17.Remuzzi G, Perico N, De Broe ME. Tubulointerstitial Diseases. In Brenner & Rector's The Kidney, 8th ed.; Brenner BM, ed; Philadelphia, PA: Saunders; 2008. p. 1174-202.  Back to cited text no. 17
18.Sant SM, Purandare NM. Autopsy Study of Cases of Snake bite with Special Reference to the Renal Lesions. J Postgrad Med 1972;18: 181-8.  Back to cited text no. 18
19.Sitprija V, Suvanpha R, Pochanugool C, Chusil S, Tungsanga K. Acute Interstitial Nephritis in Snake bite. Am J Trop Med Hyg 1982;31:408-10.  Back to cited text no. 19
20.Indraprasit S, Boonpucknavig V. Acute interstitial nephritis after a Russell's viper snake bite. Clin Nephrol 1986;25:111.  Back to cited text no. 20
21.Gundappa RK, Sud K, Kohli HS, et al. Snake bite induced acute interstitial nephritis: Report of a rare entity. Ren Fail 2002;24:369-72.  Back to cited text no. 21

Correspondence Address:
Vishal Golay
Department of Nephrology, Institute of Postgraduate Medical Education and Research, Kolkata
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.103573

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