Renal Failure

ISSN: 0886-022X (Print) 1525-6049 (Online) Journal homepage: http://www.tandfonline.com/loi/irnf20

Snakebite-Induced Acute Kidney Injury: Data from

Southeast Anatolia

Ramazan Danis, Sehmus Ozmen, Mustafa Kemal Celen, Davut Akin, Celal
Ayaz & Orhan Yazanel

To cite this article: Ramazan Danis, Sehmus Ozmen, Mustafa Kemal Celen, Davut Akin, Celal
Ayaz & Orhan Yazanel (2008) Snakebite-Induced Acute Kidney Injury: Data from Southeast
Anatolia, Renal Failure, 30:1, 51-55, DOI: 10.1080/08860220701742021

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 Renal Failure, 30:5155, 2008
Copyright Informa Healthcare USA, Inc.
ISSN: 0886-022X print / 1525-6049 online
DOI: 10.1080/08860220701742021

CLINICAL STUDY
LRNF

Snakebite-Induced Acute Kidney Injury: Data from Southeast Anatolia

Ramazan Danis and Sehmus Ozmen

Snakebite-Induced Acute Kidney Injury

Dicle University School of Medicine, Department of Nephrology, Diyarbakir, Turkey

Mustafa Kemal Celen

Dicle University School of Medicine, Department of Infectious Disease, Diyarbakir, Turkey

Davut Akin
Dicle University School of Medicine, Department of Nephrology, Diyarbakir, Turkey

Celal Ayaz
Downloaded by [42.109.168.205] at 23:41 06 September 2017

Dicle University School of Medicine, Department of Infectious Disease, Diyarbakir, Turkey

Orhan Yazanel
Dicle University School of Medicine, Department of Nephrology, Diyarbakir, Turkey

low albumin, and DIC should be closely followed up for the

Renal failure is an important complication of snakebite and
a major cause of mortality. We aimed to study the clinical profile
of snake envenomation in Southeast Anatolia, Turkey, in an adult
population. We retrospectively analyzed the records of 200
snakebite victims from 1998 to 2006 at the Dicle University
School of Medicine, Diyarbakir, Turkey. Sixteen patients (8%)
developed AKI (acute kidney injury). Of those, 25% required
dialysis and 18% died. There was no difference between groups
in age, arrival time to hospital, and hospital stay time. Both
groups received similar hydration and therapy at admission. Dis-
seminated intravascular coagulation (DIC) was observed in 25%
of the AKI group and was significantly higher than the non-AKI
group (7.1%; p = 0.014). There was no significant difference
regarding hemoglobin, platelet levels, and prothrombin time at
admission. The prevalence of thrombocytopenia (<150,000 K/
UL ) was 60% in the AKI group and 40% in the non-AKI group
(p > 0.05). WBC count was significantly higher in the AKI group
than in those without AKI (p = 0.001); serum albumin was sig-
nificantly lower in the AKI group than in those without AKI (p =
0.013). AKI is an important complication of snakebite that may
lead to mortality. Despite some troublesome aspects due to its
retrospective design, this is a large series from Southeast Anato-
lia of Turkey in an adult population. Subjects with high WBC,
Address correspondence to Dr. Ramazan Danis, Dicle Uni-
versity School of Medicine, Department of Nephrology, 21280,
Diyarbakir, Turkey; Tel.: +90 412 2488001 (4172); Fax: +90 412
2488440; E-mail: drdanis@dicle.edu.tr
development of AKI.
Keywords snakebite, acute kidney injury, viperidae,
disseminated intravascular coagulation
INTRODUCTION
There is a broad clinical spectrum of renal involve-
ment in snakebite. Besides the local and systemic symp-
toms, clinical renal manifestations vary from mild
proteinuria, hematuria, and pigmenturia to acute renal fail-
ure. Renal failure is an important complication of snake-
bite and a major cause of mortality. Renal involvement
depends on the type of snake, the degree of envenomation
and duration of exposure to the venom. Snakebite eveno-
mation is one of the etiological factors for acute renal fail-
ure (ARF) in developing countries. The incidence of
kidney dysfunction due to snakebite evenomation is 1.4
28%. The commonest species associated with renal lesions
are Russells viper, Echis carinatus, puff adder, and sea
snake.[1,2]
The viper is the most common poisonous snake in this
region of Turkey. In viper bite, renal failure may accom-
pany intravascular hemolysis or intravascular coagulation.
Hemoglobinuria and hematuria are observed. Hemolytic

51
 52 R. Danis et al.
uremic syndrome has been reported following hemotoxic
snake envenomation.[3]
The early administration of antivenom is a vital thera-
peutic measure. The timely administration of antivenom
completely reverses all clinical manifestations of systemic
envenomation.[4] The maintenance of fluid and electrolyte
balance, antibiotics, and tetanus toxoid are other therapeutic
measures.
We retrospectively analyzed the records of snakebite
victims from 1998 to December 2006 at the Dicle Univer-
sity School of Medicine, Diyarbakir, Turkey.
SUBJECTS AND METHODS
This retrospective study was carried out at the
Dicle University School of Medicine, Diyarbakir,
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Turkey. Our hospital is a referral hospital in Southeast
Anatolia, Turkey. Patients with a diagnosis of snakebite
were included. The records of snakebite victims from
1998 to 2006 were obtained from the records of the
hospital.
Even though RIFLE criteria are a new and more
standardized system, the current study is retrospective
in design, and we were not able to apply all of the
RIFLE criteria to define acute kidney injury (AKI).
Therefore, AKI was defined as serum creatinine
exceeding 150 mmol/L in males and 120 mmol/L in
females corresponding to a GFR of 5060 mL/minute in
the first 72 hours after envenomation with subsequent
recovery of GFR. Patients who did not improve their
GFR were carefully screened, and clinical and/or labo-
ratory evidence of chronic kidney disease were
excluded from the analysis. Chronic kidney disease was
defined as baseline serum creatinine (previous to the
accident) greater than 150 mmol/L in males and 120
mmol/L in females, renal ultrasound with decreased
kidney length, loss of the corticomedullary distinction,
and/or history of active or past renal disease. At admis-
sion, all patients were hydrated with an alkalinizing
solution up to 3 to 6L/day, according to clinical picture.
Hydration with an alkalinizing solution was used to pre-
vent renal injury by rhabdomyolysis. Tetanus toxoid
was applied to all cases.
Clinical Parameters
Age, gender, history of chronic diseases (e.g., heart
failure, hypertension, or diabetes mellitus), use of con-
comitant drugs, hospitalization time, dialysis treatment,
and mortality were all recorded.
Laboratory Evaluation
Complete blood count, differential cell count,
fibrinogen, fibrin degradation products (FDP), alanine
aminotransferase (ALT), aspartate aminotransferase
(AST), serum electrolytes (sodium, potassium), serum
urea and creatinine levels, creatinine phosphokinase
(CK), and lactate dehydrogenase (LDH) were measured
by standard methods. Hemoglobin (Hb) level, white
blood cell (WBC), and platelet counts were measured by
hemocounter (Cell-Dyne 3700, Abbott, Illinois, USA)
and Cell-Dyne 4000 (Abbott). Prothrombin time (PT),
activated partial thromboplastin time (aPTT), and
fibrinogen were made by coagulometry (ACL Advance,
Lexington, Kentucky, USA). All other parameters were
studied using an autoanalyzer (Abbott Aeroset, Osaka,
Japan, 1999).
Statistical Analysis
Results were expressed as mean standard devia-
tions. The comparison between groups was performed by
using the Students t-test for parametric values and chi-
square for frequencies. We used Fishers exact test values
for frequencies lower than 5. A p value <0.05 was consid-
ered statistically significant.
RESULTS
Analyzed Sample
The records of the 200 snakebite victims from 1998 to
December 2006 were obtained from the records of the hos-
pital. Time from snakebite to specific antivenom adminis-
tration was 3.2 1.9 hours in a subject with AKI and 2.8
2.1 hours in a subject without AKI (p > 0.05). Mean age of
patients was 40.3 18.8 years with AKI and 34.5 16
years without AKI group.
Comparison of the ARF and Non-ARF Groups
Of the 200 patients studied, 16 (8%) had AKI in the
first 72 hours after the snakebite. Of these, four patients
required dialysis (25%), and three (18 %) died. Mean time
to arrival at our hospital after the bite was 3.2 1.9 hours
in patients with AKI and 2.7 2.1 hours those without
AKI (p > 0.05). The mean duration of the hospital stay
was 6.6 3.6 days in patients with AKI and 7.8 4.0 days
in those without AKI.
 Snakebite-Induced Acute Kidney Injury 53

Patients Data
There was no difference between groups regarding
age, arrival time to hospital, and hospital stay (see Table 1).
Both groups received similar hydration and therapy at
admission. All detectable bites were seen on exposed parts
of the body: 99 (26%) on the foot, 77 (20%) toe, 74 (19%)
fingers, 64 (17%) hands, 41 (11%) legs, 21 (6%) arms, and
two faces. Death was due to sepsis (n = 1), multiorgan
failure (n = 1), and anaphylactic reaction (n = 1).
Laboratory Evaluation of Rhabdomyolysis
Serum CK levels were high in both groups. But the
difference was insignificant. The number of subjects with
a CK increased five-fold of upper limits was higher in the
AKI group than the non-AKI group, though the difference
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WBC were significantly higher in the AKI group when
compared to the non-AKI group (p = 0.001). None of the
patients had hemorrhage.
DISCUSSION
Snakebite evenomation is not an uncommon etiological
factor for acute renal failure (ARF) in developing countries.
Nearly all venomous snakes in Turkey and Southeast
Anatolia are members of the Viperidae family and show
poisonous local and hematoxic effects. Venomous snakes
seen in Turkey are subgroups of V.ammodytes, V. barani, V.
ursunii, V. raddei, V. kaznokovi, V. pontica, V. wagneri, V.
labetina, V. xanthina, Walterinnesea aegyptia, Malpolon
monspessulanus, and Telescopus fallaks. Most snakebites
are caused by non-venomous snakes.[5]

was insignificant.
Prevalence of ARF

Hematology and Coagulation Time The prevalence of AKI our study was 8% (n = 16) and
mortality rate of AKI was 18% (n = 3). Dialysis was required
There was no significant difference regarding hemo- in 25% (n = 4) patients. The remaining 13 patients recovered
globin, platelet levels, and prothrombin time at admission. their renal functions completely, and no patient remained
The prevalence of thrombocytopenia (<150000 K/UL) was dialysis-dependant. The significant recovery of the GFR in
60% in AKI group and 40% in non-AKI group (p > 0.05). almost all patients of the ARF group confirmed the acute
nature of the renal insult. The incidence of acute renal failure
caused by these snakes varies from 5% to 29%, depending on
Table 1 the species of snake and the severity of envenoming.[68] The
Characteristics of patients with snakebite highly venomous snakes most commonly encountered are
AKI(+) AKI(-) p
Russells viper (subfamily viperinae), snakes of the bothtrops
species (subfamily crotalinea), and rattlesnakes. The inci-
Age (years) 40.3 18.8 34.5 16 NS dence of ARF following Russells viper bite has been esti-
Sex (F/M) 8/8 97/87 NS mated to be 1332%,[1] and the prevalence of ARF following
Urea (g/dL) 113 78 38 14 p < 0.001 bothtrops snakebite ranges from 210%.[68].
Creatine (mg/dL) 2.85 2 0.7 0.2 p < 0.001 In a retrospective study of 360 patients envenomed with
Albumin (g/dL) 2.9 05 3.7 0.8 p = 0.013 echis carinatus (saw-scaled viper), 62 (17%) patients devel-
LDH (U/L) 375 224 304 144 NS
oped acute renal failure (ARF), 44 patients (71%) needed
AST (U/L) 71 57 37 34 p = 0.002
dialysis, and 16 patients (25%) died.[9] Another prospective
ALT (U/L) 45 38 31 31.7 NS
CK (U/L) 545 652 369 635 NS observational study of 100 patients envenomed with crotalus
LDH (U/L) 375 224 304 144 NS durissus was reported, showing a 29% prevalence of ARF.
DIC (%) %25 %7.1 p = 0.014 Of those, 24% required dialysis and 10% died.[10] The preva-
WBC (K/UL) 19.3 3.7 14.5 5.4 p = 0.001 lence of ARF was reported to 28.6% after viperedia family
Hb (g/dL) 13.2 3.4 13.2 2.5 NS snake bites in India, yet antivenom administration rate was
Plt (K/UL) 138 137.9 175 96 NS only 8% in these patients.[1] The low prevalence in our study
PTZ (sn) 17.1 2.9 15 3.3 NS may be due to early and high antivenom administration rate.
CRP (mg/dL) 26.8 22.5 18.4 20 NS
Arrival time to 3.2 1.9 2.8 2.1 NS
hospital (hours) Risk Factors for Development of ARF
Duration of 6.7 3.6 7.82 4 NS
hospitalisation (day)
The finding that the delay to administer an adequate
AV dose 2.3 0.7 2.3 1.7 NS
dose of the antivenom increases more than 10 times the
 54 R. Danis et al.
risk of developing ARF.[10] Previous studies have already
suggested that there is a correlation between renal injury
and time interval between the snakebite and the administra-
tion of antivenom.[1113] Although no significant difference
was present between the AKI and non-AKI groups, a possi-
ble factor related to the development of renal injury might
be the administration of less antivenom in the AKI group. In
the literature, it has been shown that early administration of
antivenom reverses clinical manifestations of snakebite.[4]
Although the time interval from snakebite to antivenom
administration was higher in the subject with AKI than the
subject without AKI, the difference was not statistically sig-
nificant (p > 0.05). However, although we believe that the
timing for the application of antivenom may be important in
prevention of renal failure, we were not able to calculate
antivenom per body surface in our patients due to the retro-
spective nature of the study. Arrival time to hospital
(3.2 1.9 hours in AKI, vs. 2.8 2.1 hours) was similar
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with that reported in literature (i.e., 13 hours).[14,15]
Disseminated intravascular coagulation (DIC) is a consis-
tent feature in patients bitten by several species of snakes.[4,9]
Viper venom produces the activation of factor V with fibrinol-
ysis, leading to DIC. This can result in hemorrhage, hypov-
olemia, and thrombin in the microvasculature and glomerular
capillaries and a microangiopathic hemolytic anemia with
subsequent ARF.[16] DIC plays a major pathogenetic role in
the renal lesions of snakebite-induced cortical necrosis.[4,16]
DIC was observed in the 25% of AKI group and was signifi-
cantly higher than the non-AKI group (7.1%) (p = 0.014).
Rhabdomyolysis is a well-known cause of renal
injury.[17,18] The clinical diagnosis of rhabdomyolysis is
established when CK increases five or more times above
normal levels, with a suggestive clinical picture and without
heart and/or cerebral injury. Serum CK levels were increased
in both groups, but the difference was insignificant. The per-
centage of subjects with a CK increased five-fold of upper
limits was higher in AKI group than non-AKI group, though
again the difference was insignificant. A previous study
reported high rhabdomyolysis prevalence in ARF group.[10]
The insignificance in our study regarding the prevalence of
rhabdomyolysis may be due to a low number of subjects
with AKI or extracellular volume expansion administration
to our all subjects. Because the most effective measure for
the prevention of ARF induced by rhabdomyolysis is extra-
cellular volume expansion with saline solution combined
with sodium bicarbonate and mannitol.[18,19]
It was observed that children have a prevalence of
ARF almost three times higher than adults. Compara-
tively, children have a lower blood volume and smaller
body surface, which might be related to a more severe
clinical picture due to an increase concentration of the
venom.[20] There was no significant difference between
AKI and non-AKI groups regarding age in our study.
ARF Characteristics
The onset of renal failure is a few hours to several
hours after the bite, suggesting that the direct nephrotoxicity
of the venom shown experimentally might also be clinically
present.[21] In our study, AKI often occurred within the first
24 to 48 hours. Six of the AKI patients were oligoanuric
(37.5%), the others patients nonoligouric (62.5%). Dialysis
treatment was indicated in 25% of our cases with AKI. The
need for dialysis is similar with that reported by Pinho
et al.[10] (24%) but lower than previous studies that reported
a greater demand for dialysis, ranging from 6877% of the
patients.[12] This discrepancy is probably related to the low
specifity of ARF diagnostic criteria used in these studies,
only identifying the more severe cases of renal injury. Renal
function was recovered in individuals who survived ARF.
Mortality in snakebite acute renal failure range from
1% to 26.5%, depending on the studies series.[1,10,12,21,22]
The mortality rate was 25% in our patients and compatible
with the literature.
The presence of DIC is significantly higher in the AKI
group than the non-AKI group (p = 0.014). Viper bite can
cause mild renal failure.[23] A low demand for dialysis in
our study supports this finding. WBC count was signifi-
cantly higher in the AKI group than those without AKI (p =
0.001), and serum albumin was significantly lower in the
AKI group than those without AKI (p = 0.013). Because
albumin is a relatively slow-reacting negative acute-phase
reactant that may be associated with high mortality in acute
renal failure,[24] serum high WBC and low albumin may
reflect the severity of inflammation in our cases.
CONCLUSION
AKI is an important complication of snakebite and a
may lead mortality. Although it has some troublesome
aspects due to its retrospective design, this is a large series
from Southeast Anatolia of Turkey in an adult population.
Subjects with high WBC or low albumin or those compli-
cated with DIC should be closely followed up for develop-
ment of AKI.
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