THE AMERICANJOURNALOF TROPICALMEDICINE ANDHYGIENE Vol. 24. No.

4
Copyright ID 1975 by The American Society of Tropical Medicine and Hygiene Printed 1,, U.S.A.

ACUTE RENAL FAILURE FOLLOWING SNAKEBITE*

K. S. CHUGH, B. K. AIKAT, B. K. SHARMA,

S. C. DASH, M. THOMAS MATHEW, 4@mK. C. DAS
Division of Nephrology, Pathology, and Hematology, Postgraduate
Institute of Medical Education and Research, Chandigarh, India

Abstract. Eight patients with acute renal failure following snakebite were studied. Intra
vascular hemolysis and disseminated intravascular coagulation contributed to the develop
ment of acute renal failure in 6 patients. Direct nephrotoxicity causing acute renal failure
is postulated in 2 patients, 1 of whom also revealed evidence of mild, disseminated intra
vascular coagulation. Three patients had histopathological lesions of acute symmetrical cortical
necrosis and 3 had acute tubular necrosis. In 1 patient with acute tubular necrosis, in whom
direct nephrotoxicity seemed to be responsible for renal failure, the striking histological
feature was a uniform debasement and disappearance of tubular epithelium. In 2 patients
with a clinical course of acute tubular necrosis, histological lesions could not be documented.
All the 5 patients with acute tubular necrosis regained full recovery of renal function, 3 of
them with the help of dialysis and 2 with conservative management. None of the 3 patients
with acute cortical necrosis survived in spite of intermittent dialysis therapy.

Snakebite poses a serious health hazard to the to viper bite is scanty.8@° The present report
inhabitants of tropical and subtropical regions of highlights clinical, hematological and histopatho
the world, although the problem is not limited to logical findings in eight patients who suffered
them alone. The world mortality from snakebite acute renal failure following viper bite.
has been estimated at 30,000 to 40,000 annually,1
out of which 15,000 deaths occur in the Indian MATERIALS AND METHODS
subcontinent alone.2 High mortality figures have During the years 1964 to 1973, 69 patients with
also been reported from Burma, Ceylon, Thailand, snakebite were admitted to the Postgraduate
Malaysia and Brazil. Medical Institute, Chandigarh, situated in the
The most important venomous snakes in India northwestern part of India. Eight of these cases
are the cobras and kraits (family : Elapidae), (1 1.6%) presented with acute renal failure. De
Russell's viper and the saw-scaled viper (family: tailed biochemical, hematological, and histopatho
Viperidae), and the pit viper (family: Crotalidae).2 logical investigations were carried out in all of
Because of a high concentration of ‘neurotoxins' them.
in the venom of elapid family snakes, the usual Identification of snake. In two cases (Nos. 1
clinical presentation is neuromuscular paralysis and 3) the snakes were killed and subsequently
which may lead to death from respiratory failure. identified as Russell's vipers. In five cases (Nos.
The viperid and crotalid bites, on the other hand, 2, 4, 6, 7, 8) the identification of the snake
produce shock, intravascular hemolysis, and bleed depended upon the description given by the
ing due to coagulation defects.' patient himself or by the witnesses, supported by
Renal involvement either due to direct toxic the clinical features. The available evidence in
damage, or secondary to shock, hemorrhage and these five cases also pointed to bites by Russell's
hematological abnormalities produced by venoms vipers. In one case (No. 5) description of the
of many snakes, has been described.37 but the snake was not available, but clinical and hemato
reported experience with acute renal failure due logical findings indicated that it had been a viper.
Biochemical data. Serial estimations of blood
Accepted 16 November 1975. urea, serum creatinine, sodium, potassium, chlo
ride, and biirubin were carried out in all the
4 Address reprint requests to: Dr. K. S. Chugh,
patients.
Associate Professor and Head, Division of Nephrol
ogy, Postgraduate Institute of Medical Education and Hematological data. Hematological investiga
Research, Chandigarh, India. tions, carried out before the institution of any
692
 ACUTE RENAL FAILURE FOLLOWING SNAKEBITE
Clinical and histological findings in eight cases of viper bite
between
bite and
Case
no.Age/sexLocal signsInterval
(days)Outcome135/MEcchymosis
edema6—8+++++3ATN28Recovered226/MFang
and
marks
edema6—8+++6?ATNt7Recovered312/MFang
and
marks4—5+++—24?ATNt14Recovered432/MEdema
and
bleeding8—10+——2ATN16Recovered520/FEcchymosis
edemaImmediate-f-++-12ACN5Died649/MFang
and
marks2—3-@--@-+±12ATN20Recovered715/MFang
marks3-4--±6ACN15Died813/MEdema
and
bleedingImmediate+——14ACN14Died
* ATN, acute tubular necrosis; ACN,
t Renalbiopsytissueinsufficientfor interpretation.
therapy, included hemoglobin, hematocrit, reticu
locyte count, platelet count, and peripheral smear
examination for red cell morphology.― Investiga
tions carried out to detect abnormalities of
hemostasis were bleeding time by the Ivy method,
clotting time by Lee and White's technique,
Hess' capillary test, one stage prothrombin time
and prothrombin index, partial thromboplastin
time with kaolin,'2 plasma recalcification time,13
fibrinogen content,'4 fibrin degradation products,'5
and estimation of factor V'6 and factor VIII.'T
Renal histology. Histopathological
the kidney were studied in percutaneous renal
biopsy material from three patients and at autopsy
in three patients. In two patients (cases 2 and 3)
the renal biopsy tissue was insufficient for histo
pathological interpretation.
OBSERVATIONS
Clinical data. There were 7 male
1 female. Their ages varied between 12 and 49
years. All of them received polyvalent antivenin
either in the hospital or prior to admission. The
site of the bite was on a lower extremity in all.
Local signs in the form of fang marks, edema,
ecchymosis, or cellulitis were present in all the
cases at the time of admission. Bleeding mani
festations in the form of bleeding from gums,
epistaxis, or hematuria were present in all except
693
TABLE 1
between
bite and of renal
signs manifes oliguria failure
(hrs)Bleeding binuriaJaundiceInterval
tationsHemoglo (hrs)Histology'Duration
acute cortical necrosis.
case 7. Two patients (cases 1 and 2) had jaundice
at the time of admission and in three others
(cases 4, 6, 7) there was a history of jaundice
following the bite and prior to admission. There
was no evidence of involvement of the central
nervous system in any of the cases. Two patients
recovered on conservative treatment but six re
quired the help of dialysis. Hemodialysis was
performed with R. S. P. model of Travenol unit
or with ‘Kills' dialyser in five patients, and
peritoneal dialysis in one.
lesions in The time interval between the snakebite and
onset of oliguria varied from a few hours to 24
hours. The interval between the onset of oliguria
and the beginning of the diuretic phase or death
varied from 5 to 28 days (Table 1). Of the
patients who required dialysis because of several
renal failure, cases 4 and 5 were dialysed once
only. Cases 1 and 6 were dialysed twice, and
patients and cases 7 and 8 required 3 hemodialyses each. Two
patients (cases 2, 3) who did not require dialysis
and three of the dialyzed patients (cases 1, 4, 6)
recovered completely. Cases 5, 7, and 8 died
while on dialysis.
Hematological data. The results of hematologic
investigations including coagulation and fibrino
lysis studies have been charted in Table 2. Severe
anemia was present in five patients (cases 1, 5,
6, 7, 8) and mild anemia in the remaining three
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694 CHUGH ET AL.

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15) v 1 and 2. 1 . Renal biopsy specimen from
2 a viper bite fatality. Shown are degeneration of
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u@0 0 C@0FIGURES tubules with marked interstitial ed,ma and islands of
a —oo I-
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damage following viper bite. Uniform debase
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F-Renal
patients. Five patients had haemoglobinuria
(Table 1—cases 1, 2, 3, 5, 6) but overall
intravascular hemolysis in the form of jaun@
@ “ bloot@2
e@ @-j,ia4
.!of dice, reticulocytosis or abnormal peripheral
film was present in six patients (cases 1—6).
@ ‘°
were morphological abnormalities of the
erythrocytes such as crenated and fragmented
@-:
@ F-@ 0 0 red cells, significant numbers of spherocytes@
@ m:@ so o u@ @.,O 5/1
variable aniso and poikilocytosis, and abnor.@
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malities in coagulation and fibrinolysis (casea
@‘ 0' ‘@ 0 0 “@ 0 0 @) C
@ dá@ ;@ 1—5), all suggesting the presence of disseminated
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intravascular coagulation in these patients.
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Biochemical investigations. Blood urea ranged
@
@
@ ,@‘
r@i i- — “@ e@i‘-C C between 77 and 330 mg/100 cc and serum creati
@ ‘@i8
0 nine between 3.3 and 13.0 mg/100 cc at the height
‘i0 q of renal failure. The serum electrolytes were@
“s@Osow
within normal limits in seven cases. One patient
(case 7) showed severe hyponatremia. Serum
@
@ ,C,@C,) S .5- .51- Co)There
,@“ biirubin was raised in two patients (cases 1, 2)@
 ACUTE RENAL FAILURE FOLLOWING SNAKEBITE 695

TABLE 3
Results of blood biochemical investigations in eight cases of viper bite

cc1133.54.4901833012.931.221323.59823.5773.35.531305.0902130013.01.841334.396222208.30.7551304.995201607.81.061324.4952229710.80.7571103.610322.531211.70.8581384.910126383
Case no.Na mEq/LK mEq/LCl mEq/LHCO mEq3/LL'rea tng/l00 ccCreatininemg/100 ccBilirubin
mg/100

In others, it was normal at the time of admission.

The details of the results of biochemical inves
tigations have been charted in Table 3.
Histology. The morphological changes in two
renal biopsy specimens obtained during early
diuretic phase (cases 1, 6) revealed degeneration
of tubules with marked inter-tubular edema and
islands of regeneration (Fig. 1) in both. The
striking features in the renal biopsy tissue of
case 4 was debasement and disappearance of the
tubular epithelium, in extensive areas bringing
out sharply the basement membrane and the
inter-tubular connective tissue, both of which
stained brightly with PAS stain (Fig. 2). Bilateral
massive cortical necrosis was observed in three
patients (cases 5, 7, 8). The characteristic ghost
like appearance of glomeruli and tubules in the
necrotic areas (Fig. 3) was a common feature in
all the three cases. In addition marked vascular
and parenchymal congestion was seen in one case.
This case also showed fibrin thrombi in the
vessels (Fig. 4). The surviving glomeruli showed
fibrin thrombi and some proliferation of mesangial
cells(Fig.5).
A clinical follow-up of the five patients who
recovered was carried on for 6 years following
envenomation. In each instance the patient has
maintained normal renal function.

-)C

FIGm.mzs 3 to 5. 3. Illustration of the characteristic

ghost-like appearance of glomeruli and tubules in a
fatal case of viper bite. This finding suggests diffuse
cortical necrosis. 4. Fibrin thrombi in a case of
acute renal cortical necrosis following viper bite. 5.
Fibrin thrombi and proliferation of mesangial cells
in one of the surviving glomeruli of a case of diffuse
cortical necrosis caused by viper bite. 3 and 4, X 96;
5, x 385.
 696 CHUGH ET AL.

TABLE 4
Renal histological lesions reported in patients with acute renal failure following snakebite

of of
snakePathologyAzevedo
AuthorsNo. patientsType

(Autopsy)Efrati
and Teixera (1938)'1CobraSymmetrical cortical necrosis
(Autopsy)Amorim
and Reif (1953)214Palestinian viperGlomeruli stuffed with RBCs
(Autopsy)Marsden
and Mello (1954)@3RattlesnakeNecrosis of distal tubules
(Autopsy)Oram
and Reid (1961)°3Sea snakeNecrosis of distal tubules
(Biopsy)Varagunam
et al. (1963)°1Sand viperCortical necrosis and caldfication
(Autopsy)Sant and Panabokke (1970)101Pit viperAcute cortical necrosis
and Purandare (1972)2010*? ViperProliferative glomerulonephritis —6]
Cortical necrosis —3 @.
(Autopsy)
JPresent Interstitial hemorrhagic nephritis—1
series6tIndian Russell's cortical necrosis—3(Autopsy)
viperAcute Acute tubular necrosis—3(Biopsy)
* The total number of patients discussed was 14 but 4 showed only basement membrane thickening.
t Total numberof patientsobservedwas eight but resultsof histologicalstudy wereavailablefor 6 patientsonly.

DISCUSSION of intravascular hemolysis in 6, microangiopathic

The venom of snakes of the family Viperidae, hemolytic anemia in 2 and disseminated intra
to which the Indian Russell's viper belongs, con vascular coagulation in 5 patients. All these
sists of a mixture of toxic proteins and enzymes factors either singly or in combination could have
which have hemotoxic and necrotising properties. contributed to the development of acute tubular
Intravascular hemolysis which is produced by necrosis and acute cortical necrosis in six of our
these snakes has generally been attributed to the patients. Acute renal failure in two of our pa
action of ‘phospholipaseA' content of the venom,18 tients who became totally anuric (case 4 with
and anticoagulant, fibrinolytic, antithromboplastic acute tubular necrosis showing uniform debase
as well as enhancement of plasminogen activity ment and disappearance of tubular epithelium
to the ‘proteases.'1°Six of our patients showed and case 7 with symmetrical cortical necrosis)
evidence of intravascular hemolysis in the form immediately after the bite was possibly due to a
of jaundice, hemoglobinuria or abnormalities in predominant nephrotoxic action of the venom,
the peripheral blood film. A bleeding manifesta although in one of these (case 4) mild intra
tion, which occurs frequently following bites by vascular hemolysis and disseminated intravascular
vipers, was present in all except one patient. coagulation may also have contributed to the
Pathological findings in the kidney including development of renal lesions. A direct toxic
acute tubular necrosis,4 6 bilateral diffuse cortical action on the kidney by the venom of the viper
@ necrosis,3 @o 20proliferative glomerulonephritis,2° and pit vipers which has ‘vasculotoxic' properties
hemorrhagic glomerulonephritis,2' and hemor has been suggested in the past in some cases by
rhagic interstitial nephritis'° have been reported Reid.@ Varagunam and Panabokke postulated
in patients who have had acute renal failure that the direct nephrotoxic effect is presumably
following snakebite. Data concerning the 23 pre due to the absorption of the venom from the site
viously documented cases, and six of the eight of the bite into the blood stream and a very high
patients studied by us are given in Table 4. concentration being achieved in the kidneys
The pathogenesis of acute renal failure follow because of their profuse blood supply.1°
ing snakebite has been generally attributed to The role of various dialysis procedures in
hemorrhage leading to circulatory failure, shock controlling biochemical abnormalities of acute
and collapse,°acute intravascular hemolysis,° and renal failure, irrespective of etiology, is well
disseminated intravascular coagulation and defi known. It is possible that dialysis has been con
brination syndrome.8 The detailed hematological ducted in many cases of acute renal failure
investigations of our patients revealed evidence following snakebite, but only three such instances
 ACUTE RENAL FAILURE FOLLOWING SNAKEBITE 697

have been reported. Danzig et al.23 reported the 9. Oram, S., Ross, G., Pell, L., and Winteler, J.,
first case of acute renal failure after a snakebite 1963. Renal cortical calcification after snake
bite. Br. Med. J., 1: 1647—1648.
treated successfully with hemodialysis. The other 10. Varagunam, T., and Panabokke, R. G., 1970.
two patients reported recently had developed Bilateral cortical necrosis of the kidneys fol
acute renal failure and hyperkalemic paralysis lowing snakebite. Postgrad. Med. J., 46: 449—
following sea snakebite and recovered completely 451.
11. Dacie, J. V., and Lewis, S. M., 1963. Practical
after hemodialysis.24 Five patients with acute
Hematology, 3rd edition. J. & A Churchill,
tubular necrosis in the present series recovered Ltd., London.
completely, 3 with the aid of dialysis and 2 on 12. Dacie, J. V., and Lewis, S. M., 1969. Practical
conservative therapy. None of the three patients Hematology, 4th edition. J. & A. Churchill,
with acute symmetrical cortical necrosis observed Ltd., London.
13. Owen, C. A., Jr., Mann, F. D., Hum, M. M.,
by us, survived in spite of their having been on
and Stickney, J. M., 1955. Evaluation of dis
intermittent dialysis regime. A patient with orders of blood coagulation in the clinical
patchy cortical necrosis caused by a saw-scaled laboratory. Am. J. Clin. Pathol., 25: 1417—
sand viper bite is known to have survive! for 7 1426.
14. Ratnoff, 0. D., and Menzie, C., 1951. A new
months.° Patients with acute renal failure due
method for the determination of fibrinogen in
to snakebite, therefore, like any other patient small samples of plasma. J. Lab. Cliii. Med.,
with acute renal failure, should continue to be 37: 316—320.
treated with hemodialysis until irreversibility of 15. Morskey, C., Lalezari, P., and Johnson, A. J.,
the underlying lesion such as bilateral symmetrical 1969. A rapid, simple, sensitive method for
measuring fibninolytic split products in human
cortical necrosis has been proved beyond doubt.
serum. Proc. Soc. Exp. Biol. Med., 131: 871—
875.
ACKNOWLEDGMENTS 16. Quick, A. J., 1960. The assay and properties of
labile factor (factor V). J. Clin. Pathol., 13:
The authors are grateful to Dr. Hugh L.
457—462.
Keegan, University of Mississippi Medical Cen 17. Das, K. C., and Aikat, B. K., 1966. A method
ten, Jackson, Mississippi, for assistance with the for the assay of factor VIII without haemo
manuscript. philic plasma. Indian J. Med. Res., 54: 1138—
1144.
18. Russell, F. E., and Puffer, H. W., 1971. Phar
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