Blackwell Publishing AsiaMelbourne, AustraliaNEPNephrology1320-5358© 2006 The Author; Journal compilation © 2006 Asian Pacific Society of Nephrology2006115442448Review ArticleSnakebite

nephrologyV Sitprija

NEPHROLOGY 2006; 11, 442–448 doi:10.1111/j.1440-1797.2006.00599.x

Review Article

Snakebite nephropathy
VISITH SITPRIJA

Queen Saovabha Memorial Institute and King Chulalongkorn Memorial Hospital, Bangkok, Thailand

SUMMARY: There is a broad clinical spectrum of renal involvement in snakebite. Besides the local and sys-
temic symptoms, clinical renal manifestations vary from mild proteinuria, haematuria, pigmenturia to acute renal
failure. Bites by haemotoxic snakes and myotoxic snakes are the common causes of renal involvement especially
acute renal failure. Therefore, renal failure is often associated with haemorrhagic diathesis, intravascular haemol-
ysis and rhabdomyolysis. Renal pathological changes include mesangiolysis, glomerulonephritis, vasculitis, tubu-
lar necrosis, interstitial nephritis and cortical necrosis. Tubular necrosis is an important pathological counterpart
of acute renal failure. Haemodynamic alterations induced by cytokines and vasoactive mediators leading to renal
ischaemia are important in the pathogenesis of acute renal failure. Haemolysis, intravascular coagulation and
rhabdomyolysis are important contributing factors. Direct nephrotoxicity can be induced by the venom through
metalloproteases and phosphilipase A2. Immunologic mechanism plays a minor role in the pathogenesis of the
renal lesion.

KEY WORDS: glomerulonephritis, haemodynamics, metalloproteases, phospholipase A2, renal failure,

snakebite.

Clinical toxicology from natural toxins is an important A highly vascularized organ, the kidney is prone to venom
health problem in the tropics. With biological diversities toxicity. Renal involvement in snakebite varies widely.7–10
and a favourable environment, tropical areas are rich in ani- Acute renal failure is frequently described and is life threat-
mals, plants, microbes and their toxins. Snake bites, animal ening. Haematuria and proteinuria are common. There is a
bites and stings are common occurrences, and snake bites broad spectrum of renal pathological changes.11–14 All renal
are the highest among animal toxin poisoning. The total structures are involved. A review of snakebite nephropathy
number of snake bites has been estimated to be 5.4 million is necessary due to the proliferation of clinical and scientific
per year, with 125 345 deaths, 100 000 of which were in data on the topic.
Asia and 20 000 in Africa.1 These data are perhaps under-
estimated due to the difficultly in accessing accurate data. CLINICAL RENAL MANIFESTATIONS
Snake venoms can cause cellular injury through
enzymes, polypeptide toxins, cytokines and mediators.2 Proteinuria, haematuria and acute renal failure are among
Important venom enzymes consist of proteases, hydrolases, the common clinical renal manifestations in snakebite.
hyaluroxidase, oxidases, phospholipases and esterases.
Among these enzymes, phospholipases A2 and proteases
(especially metalloproteases), contribute significantly to Proteinuria
tissue injury. Cytokines and vasoactive mediators are
responsible for inflammatory changes and haemodynamic Proteinuria may be observed following snakebite. Pro-
alterations that can ultimately lead to cellular injury.3–6 teinuria has been noted in rats following intrarenal injec-
The clinical symptoms in snakebite vary from local pain, tion of cobra venom.15 The incidence of proteinuria in
swelling and necrosis at the site of the bite to systemic snakebite is variable depending on the kind of snakes
involvement, including hypotension, haemorrhage, con- involved and there is also geographical variation. In a series
junctival oedema, chemosis, central nervous system symp- of 400 tropical snakebite patients proteinuria was observed
toms, myalgia, paralysis, abdominal pain and renal failure.2 in 4%.16 The magnitude of proteinuria is less than 500 mg/
24 h, and this is usually a transient finding which com-
pletely resolves when the patient recovers. However, signif-
Correspondence: Dr Visith Sitprija, Queen Saovabha Memorial
icant proteinuria over 1 g/24 h has been observed in 50% of
Institute, 1871 Rama 4 Road, Bangkok 10330, Thailand. Email:
sitprija@yahoo.com; visith@webmail.redcross.or.th Russell’s viper bite patients in Myanmar, suggesting that
Accepted for publication 13 May 2006. geographical variation can have an effect on the venom
© 2006 The Author composition of the snake of the same species.17 Despite
Journal compilation © 2006 Asian Pacific Society of Nephrology heavy proteinuria the effect is temporary and completely
Snakebite nephrology
resolves during the recovery phase. Nephrotic syndrome in
snakebite has been reported,18 but the cause and effect rela-
tionship was not substantiated.
Haematuria
Haematuria is often seen in the patient bitten by haemo-
toxic snakes, either viperid or crotalid snakes due to haem-
orrhagic diatheses, and this can be either microscopic or
gross haematuria depending upon the severity of envenom-
ation. The incidence can be as high as 35%.16 Although not
common, nephritic syndrome has been described in viper
bite with pathological changes of diffuse proliferative and
crescentic glomerulonephritis.19,20 There is some diminution
of renal function. The clinical outcome is usually favour-
able; however, with associated tubular necrosis, renal failure
can be severe.
Pigmenturia
Intravascular haemolysis is common in viperid and crotalid
snake bites. Haemoglobinuria is therefore frequently
observed in these haemotoxic snake bites. Haemolysis is
preceded by erythrocyte swelling with the rise in haemat-
ocrit.21,22 Chelation of calcium by citrate decreases erythro-
cyte swelling and raises the threshold for intravascular
haemolysis.22 Rhabdomyolysis induced by phospholipase A2
in myotoxic snake envenoming results in myoglobinuria.
Both haemoglobinuria and myoglobinuria are important in
the pathogenesis of acute renal failure in snakebite.
Acute renal failure
Snakes that cause renal failure are either myotoxic or hae-
motoxic snakes causing rhabdomyolysis, intravascular
haemolysis, disseminated intravascular coagulation (DIC)
or haemorrhage. In tropical Asia acute renal failure (ARF)
in snakebite constitutes 1.2% of total acute renal failure in
Thailand, 3% in India, and as high as 70% in Myanmar.
Children are more prone to develop renal failure than
Table 1 Snakes with nephrotoxicity
Haemotoxic snakes
Russell’s viper (Daboia russelli siamensis)
Saw-scaled viper (Echis carinatus)
Lance-headed viper (Genus Bothrops)
Puff Adder (Bitis arietans)
Pit viper (Family Crotalidae)
Rattlesnake (Genus Crotalus)
Tiger snake (Notechis scutatus)
Brown snake (Genus Pseudonaja)
Taipan (Oxyuranus scutellatus)
Moccasin (Agkistrodon piscivorus)
Boomslang (Dispholidus typus)
© 2006 The Author
Journal compilation © 2006 Asian Pacific Society of Nephrology
443
adults.23 Table 1 lists the snakes with myotoxicity and hae-
motoxicity that can cause acute renal failure. The incidence
of acute renal failure caused by these snakes varies from 5%
to 29% depending on the species of snake and the severity
of envenoming.7,23,24 The onset of renal failure is a few hours
to several hours after the bite. Renal angle tenderness may
be observed. In a series of 123 patients bitten by Russell’s
viper, renal angle tenderness was noted in 39% and
hypotension noted in 35%.24 Renal failure may not be asso-
ciated with hypotension, however, transient hypertension
has been observed. In viper bite renal failure may accom-
pany intravascular haemolysis or intravascular coagulation.
Haemoglobinuria and haematuria are observed. Haemolytic
uraemic syndrome has been reported following haemotoxic
snake envenomation.25 In myotoxic snakebite renal failure
is associated with muscular pain, weakness, myoglobinuria
and high serum creatine phosphokinase due to rhabdomy-
olysis. In both instances hyperkalaemia may be of an alarm-
ing degree. Renal failure is catabolic with rapid rises in
blood urea nitrogen and serum creatinine. Hyperuricaemia
may be present. Nonoliguric renal failure is not uncommon.
Renal failure averages 2–3 weeks in duration. Prolonged
renal failure with oligo-anuria is observed in the patient
with cortical necrosis or acute tubular necrosis associated
with either interstitial nephritis or extracapillary glomeru-
lonephritis. Acute glomerulonephritis in viper bite can
cause mild renal failure.20 The patient usually completely
recovers except for those with cortical necrosis. Mortality in
snakebite acute renal failure range from 1% to 20%.7,23,24
Bad prognosis is observed in the elderly and those with cor-
tical necrosis or severe haemorrhagic complications.10
MANAGEMENT
Specific antivenom treatment is important and this is usu-
ally given before renal failure sets in. Monovalent antiven-
oms are preferred. Phasmapheresis and blood exchange have
been used in snake envenomation where antivenom was
unavailable.25,26 However, this is not practical since it has to
be performed very early before the venom fixes to the tissue.
Either peritoneal dialysis or haemodialysis is life saving.
Myotoxic snakes
Sea snakes (Family Hydrophidae)
Mulga snake (Pseudechis australis)
Rough-scaled snake (Tropidechis carinatus)
Taipan (Oxyuranus scutellatus)
Tiger snake (Notechis scutatus)
Small-eyed snake (Cryptophis nigrescens)
444
Dialysis should be performed early and frequently. Early and
frequent dialyses are important for the patient survival.
Haemodialysis improves muscular symptoms in sea-
snakebite, and suggests that dialysis corrects hyperkalaemia
and removes some postsynaptic neurotoxin with small
molecular weight.27 Renal failure should be prevented.
Prompt treatment with specific antivenom is required.
Maintenance of good urine flow is important. Alkalization
of urine by sodium bicarbonate helps in the prevention of
acute renal failure in the patients with myoglobinuria or
haemoglobinuria provided that this is done early when dark
urine is observed or the snake is known to be myotoxic or
haemotoxic. In animal studies alkalization of urine prior to
envenomation prevents pathological changes and impair-
ment of renal function.28,29 In established acute renal failure,
administration of sodium bicarbonate and mannitol can be
dangerous and should be avoided due to fluid overload and
hyperosmololity. Dopamine and furosemide attenuated
impaired renal function in animal model of Russell’s viper
envenomation at the early stage.30 In tropical infectious dis-
ease models, dopamine and furosemide given at the prerenal
failure stage induced diuresis and prevented renal failure.
There are no clinical data in the snakebite model. Of inter-
est, hyperparathyroidectomy in a canine prior to Russell’s
viper venom administration attenuated the decrease in
glomerular filtration and renal blood flow.31
RENAL PATHOLOGY
All renal structures can be involved in snake
envenomation.
Glomerular changes
Glomerular involvement in snakebite is often overlooked.
In animal experiments focal mesangial proliferative glomer-
ulonephritis can be induced by injection of Habu snake (Tri-
meresurus flavoviridis) venom.32 Mesangiolysis is the early
appearance of the glomerular lesions.33,34 There is dissolu-
tion of the mesangial matrix. Hypercellularity of mesangial
cells appears later as a healing reaction. The mesangial pro-
liferative lesion is inhibited in the platelet-depleted animal.
Habu snake venom induced proliferation of mesangial cells
with a significant elevation of monocyte chemoattractant
protein (MCP-1) mRNA. Positive storming of MCP-1 is
shown in the marginal area of glomeruli with mesangiolysis.
Extracellular matrix glycoprotein tenascin C expression,
especially domain D and platelet-derived growth factor, are
significant in the healing process of glomerulonephritis.35,36
Vascular endothelial growth factor regulates angiogenesis
and plays an important role in capillary repair and resolu-
tion of glomerulonephritis. Over the course of the disease
mesangial cells migrate into the lesion, proliferate and form
a confluent cellular mass. Fibronectin derived from platelets
and macrophages provides a matrix with mesangial cell
migration into glomerular lesions. The venom of Bothrops
moojeni can also cause mesangiolysis, glomerular micro-
aneurysm and proteinuria in rats.37
V Sitprija
In humans, mild mesangial proliferative glomerulone-
phritis has been observed following the bite of Russell’s
viper, cobra, green pit viper and Habu snake.9 There is wid-
ening of mesangial areas due to proliferation of mesangial
cells or an increase in the amount of mesangial matrix or
both. Irregular thickening of the wall of peripheral capillary
loops may be observed. In addition, mononuclear leucocytes
and a small number of polymorphonuclear cells are occa-
sionally present within glomerular capillary lumens. This is
a non-specific finding and may be seen in other snake bites
also. Deposition of IgM and C3 in the glomeruli may be
intense, negligible or absent depending upon the time renal
biopsy is performed. IgM and C3 deposition may be absent
when renal biopsy is performed early after the bite. In most
cases in which renal biopsy was performed late in the course
of the disease, the deposition appears fine and granular and
is commonly located in the mesangial areas and sometimes
along the capillary loops.9 This is different from IgM mesan-
gial proliferative glomerulonephritis in which deposition of
IgM and C3 is more intense along the capillary loops. IgM
deposits are more prominent in Russell’s viper bite than in
cobra bite and green pit viper bite. Deposition of C3 is more
intense in cobra cases. Fibrin deposition in the peripheral
capillary loops and the Bowman’s space is observed in some
green pit viper and Russell’s viper cases. Mesangiolysis is
demonstrable in the patient bitten by Russell’s viper or
green pit viper.38
In some instances the severe form of glomerulonephritis
may occur. Extracapillary proliferative glomerulonephritis
with fibrin deposition and crescent formation without
immunoglobulins and C3 has been shown in puff adder
bite19 and Russell’s viper bite.39 Diffuse proliferative glom-
erulonephritis can be observed in occasional green pit viper
bite victims.20
Tubulointerstitial changes
Degeneration, necrosis, and regeneration of tubular epithe-
lial cells have been observed in renal failure following the
bite by either haematotoxic or myotoxic snakes.7–9,40 These
changes occur in any part of the renal tubule. Interstitial
oedema and cellular infiltration are observed. The infiltrates
consist of lymphocytes, plasma cells, and mononuclear
phagocytic cells. Interstitial lesions are more prominent in
the area where there is tubulorhexis. In haemotoxic snake-
bite fine granules of haemoglobin can be observed in the
proximal tubular cells, and haemoglobin casts are seen in
the lumen of necrotic tubules. In myotoxic snakebite the
tubules contain myoglobin casts. Mild tubular degeneration
is present in green pit viper bite and has been observed occa-
sionally in cobra bite. Tubular necrosis is the common cause
of acute renal failure in snakebite.
Acute diffuse interstitial nephritis has been observed in
Russell’s viper bite.11,12,41,42 There is diffuse and intense
interstitial infiltration with mononuclear cells out of
proportion to tubular degeneration. Immunofluorescence
study shows no deposition of immunoglobulins and
complement.
© 2006 The Author
Journal compilation © 2006 Asian Pacific Society of Nephrology
Snakebite nephrology
Vascular changes
Segmental necrotizing arteritis of the interlobular arteries
has been described in Russell’s viper bite.9,43 The lesion
could have been missed if the renal biopsy was superficial.
Segmental thrombophlebitis of the arcuate vein and its trib-
utaries has been reported in both Russell’s viper bite and
green pit viper bite.9,43 Deposition of C3 without immuno-
globulins in the wall of necrotizing arteries is demonstrable.
Deposition of C3 in the wall of afferent and efferent arteri-
oles without any vascular change has been shown in both
viper bite and cobra bite patients.
Renal infarction and cortical necrosis
In animal experiments, renal infarction has been demon-
strated following crotalid snake venom administration.44 In
human, haemorrhagic infarct has been observed in the
patients bitten by rattlesnake and Russell’s viper. Fibrin
platelet thrombi appear in interlobular arteries within or
near the infarcted areas. Necrotic tubules containing hae-
moglobin casts are demonstrable.
Cortical necrosis has been observed following the bite of
Russell’s viper, Echis carinatus, Bothrops jararaca, and Agki-
strodon hypnale.14,45–47 The lesion is associated with dissemi-
nated intravascular coagulation. There is necrosis of all
elements of the kidney with thrombi in the renal vascular
bed. In cases with recovery there is residual impairment of
renal function, and calcification of the renal cortex may be
seen by radiography.45,47
The relationship between renal pathological changes
and clinical renal manifestation is shown in Table 2.
PATHOGENESIS
The pathogenesis of renal lesions in snakebite is complex
involving both the direct action of venom on the kidney
and the inflammatory effects due to the release of various
endogenous cytokines and mediators. Phospholipase A2, an
important toxic component of the venom, stimulates
hypothalamus-pituitary and immune axes to increase ader-
enocorticotrophic hormone, corticosteroid, arginine vaso-
Table 2 Clinicopathological correlation
Pathology
Mesangiolysis
Mesangial proliferative glomerulonephritis
Diffuse proliferative glomerulonephritis
Extracapillary proliferative glomerulonephritis
(usually associated with tubular necrosis)
Vasculitis (usually associated with tubular necrosis)
Tubular necrosis
Acute diffuse interstitial nephritis(usually associated
with tubular necrosis)
Cortical necrosis
© 2006 The Author
Journal compilation © 2006 Asian Pacific Society of Nephrology
445
pressin and acute phase response.48 Histamine, kinins,
eicosanoids, platelet activating factor, catecholamines and
endothelin are among the involved mediators. Zinc metal-
loprotease can cleave glutathione-S-transferase-tumour
necrosis factor-alpha fusion protein (GST-TNF-α) substrate
to generate biologically active TNF-α.49 In a recent study of
vasoactive mediator release following Russell’s viper
envenomation the plasma concentrations of norepinephine,
epinephrine, dopamine, thromboxane B2, endothelins and 6
keto PGFα were elevated.5 Besides these vasoactive media-
tors cytokines are important in cellular interaction in a
variety of immunological and inflammatory processes.
Envenomation of mice by the venom of Bothrops asper
and Bothrops jararaca induced striking elevations of serum
TNF-α, IL-1, IL-6, IL-10 IFN-γ and NO.50,51 The effects of
cytokines and vasoactive mediators are reflected by haemo-
dynamic changes and immune response. Snake venom poi-
soning shares the same inflammatory process as infection or
sepsis with the roles of cytokines, mediators, complement
activation, reactive oxygen species and immunologic reac-
tion. Haemodynamic changes therefore play an important
role in snake envenomation. Figure 1 summarizes the patho-
genesis of nephropathy in snakebite.
SNAKE VENOM
IMMUNE
CYTOKINES
DIRECT INJURY
RESPONSE
MEDIATORS
ADHESION MOLECULES
HEMOLYSIS
MYONECROSIS
INTRAVASCULAR
INTERSTITIAL COAGULATION
NEPHRITIS
HEMORRHAGE
RBF VASCULITIS
MESANGIOLYSIS
TUBULAR NECROSIS
CORTICAL NECROSIS
GLOMERULONEPHRITIS
Fig. 1 Pathogenisis of nephropathy in snakebite. RBF, renal
blood flow.
Clinical renal manifestation
Normal renal function, normal urine finding, or haematuria
Normal renal function, normal urine finding or haematuria, or mild
proteinuria, occasional heavy proteinuria with complete resolution
Mild renal failure, haematuria, proteinuria
Severe renal failure and haematuria with prolonged
clinical course
Severe renal failure with prolonged clinical course
Acute renal failure
Severe renal failure with prolonged clinical course
Severe acute renal failure with residual damage or without recovery
446
Haemodynamic alterations
Haemodynamic changes in snakebite vary among snakes
involved. In a study of Russell’s viper envenomation in
canines, initially the cardiac output was decreased, systemic
vascular resistance (SVR) and renal vascular resistance
(RVR) was increased; the renal blood flow (RBF) and the
glomerular filtration rate (GFR) were decreased.52 Haemo-
dynamic changes are consistent with the effects of vasocon-
strictive mediators. The decreased cardiac output is believed
to be attributed to the effect of thromboxane A2 resulting in
pulmonary artery constriction and decreased blood return to
the heart. Later at 6.00 h after envenomation the cardiac
output was increased; SVR was decreased; RVR was mark-
edly increased; RBF and GFR further decreased (Fig. 2).
Haemodynamic alteration at this stage is similar to that of
sepsis with prominent effects of NO and PGI2 on systemic
circulation and the effect of vasoconstrictive mediators on
the kidney. In a sea snake study envenomation by Lapemis
hardwicke in canines revealed there was no change in car-
diac output (CO) and SVR, but RVR was increased.29 RBF
and GFR were decreased, and renal failure developed. There
was no change in renal haemodynamics when sodium bicar-
bonate was given before envenomation.29 Renal failure was
prevented. It was suggested that decreased RBF and GFR
were due to renal tubular obstruction by myoglobin. Sodium
bicarbonate prevents tubular obstruction thus maintaining
RBF and GFR. Intravenous injection of cobra venom (Naja
kaouthia) in canines decreased GFR and RBF of short dura-
tion without causing renal failure.
In isolated renal perfusion there are great variations in
venom effects not only among different snakes but also
among snakes of the same genus but different subspecies.
However, in most snake envenomations, the glomerular fil-
tration rate and renal blood flow are decreased where renal
vascular resistance is increased.53–55 In a study of Bothrop
moojeni venom, decreased RVR and increased RBF were
observed following envenomation.55 GFR remained
110
90
70
Change (%)
50
30
10
0 the C-terminal of the protein. The high affinity interaction
–10
–30
–50
2h 24 h 48 h
Post-envenomation
Fig. 2 Haemodynamic changes in Russell’s viper envenoma-
tion.
, cardiac output; , glomerular filtration rate; , renal
blood flow; , renal vascular resistance; , systemic vascular
resistance.
V Sitprija
unchanged, presumably due to the effect of natriuretic pep-
tides in the venom.55,56
Although haemodynamic changes are basic in the devel-
opment of ARF, the duration of decreased GFR and RBF
and the associated complications are important. There is
good correlation between the renal function and the
haematologic profile in viper bite.57 Additional insults
including haemoglobinuria, myoglobinuria, haemorrhage,
complement activation and reactive oxygen species play
contributing roles in prolonging the duration of decreased
GFR and RBF. Experimentally, cobra envenomation causes
the decrease in GFR and RBF of short duration without
developing ARF, while Russell’s viper and sea snake
envenomation, which cause longer duration of renal
ischaemia associated with DIC, haemoglobinuria and
myoglobinuria result in the development of acute renal
failure.29,52
Direct nephrotoxicity
Renal failure has been observed in patients a few hours after
snakebite without hypotension, haemorrhage, intravascular
haemolysis and rhabdomyolysis. The clinical evidence sug-
gests direct nephrotoxicity of the venom. Mesangiolysis,33,34
glomerulonephritis19,20,39 and vasculitis9,38 without immuno-
logic clues indicate direct glomerular and vascular injury
by the venom. Venomous snakes have enzymes that can
directly cause cellular injury. Metalloprotease can cause pro-
teolysis of the extracellular matrix and disrupts cell-matrix
and cellular adhesion. The enzymes are present in the ven-
oms of snakes in the Viperinae and Crotalinae subfamilies,58
and bind with various degrees of specificity to integrin alpha
4 beta 1, alpha 4 beta 7, alpha 5 beta 1, alpha 6 beta 1, alpha
9 beta 1, alpha V beta 3 and alpha V beta 5, expressed on
cells.59–61 Integrity of cellular junctions is disrupted as a
result of disruption of the actin cytoskeleton resulting in a
loss of cell polarity. Integrins which are critical for cellular
adhesion, redistribute away from the basal cell surface, con-
tributing to the loss of adhesion to the basement membrane.
Metalloproteases can induce apoptosis of vascular endothe-
lial cells.62 Phospholipase A2 enzymes are present in several
poisonous snakes including crotalids, viperids, elapids and
hydrophids. The enzymes are toxic and induce a wide spec-
trum of pharmacological effects. Phospholipase A2 can
cause membrane injury and tubular necrosis. The enzymes
interact with the biological membranes via a distinct molec-
ular region. This active region is likely to be formed by a
combination of basic hydrophobic amino acid residues near
of PLA2 with its target protein is probably due to the inter-
action of charges, hydrophobicity and van der Waal’s con-
tact surfaces between the toxin and the binding site as the
surface of the cell membrane.63,64 These events lead to mem-
brane destabilization and loss of permeability and cellular
necrosis. In animal experiments, Bothrops moojeni crude
venom decreases transepithelial electrical resistance across
the cultured Madin-Darby canine kidney (MDCK) cell
monolayers, causes disarray of the cytoskeleton and impairs
cell to matrix adhesion.37 Bothrops venom decreased neutral
© 2006 The Author
Journal compilation © 2006 Asian Pacific Society of Nephrology
Snakebite nephrology
red uptake of vero cells.65 Notexin from tiger snake venom
can cause renal tubular and glomerular damage within 24 h
after subcutaneous injection in mice.66 By isolated renal per-
fusion, Russell’s viper venom decreased potential difference
across the proximal tubular membrane31 and decreased
tubular re-absorption of sodium in dose-dependent fash-
ion.67 The venom causes lysis of vascular smooth muscle,
hydropic and vascular degeneration of proximal and distal
tubular cells and cortical collecting duct with detachment
from the basement membrane.68 In a cell culture study using
LLC-PK1 cells and MDCK cells representing proximal and
distal/collecting tubular cells, Russell’s viper venom caused
nuclear pycnosis and cellular detachment from the substrate
surface. Mesangial cells were completely disintegrated.68
Besides the direct injurious effects of the venom, indirect
injury can be caused by cytokines and inflammatory medi-
ators induced by both metalloproteases and phospholipase
A2 without haemodynamic changes.
Immunological mechanism
Immunologic mechanism plays a minor role in the patho-
genesis of glomerulonephritis. In contrast to glomerulone-
phritis seen without immunologic evidence in acute animal
experiments32,68 and in a number of patients bitten by
snakes,39 immune complex glomerulonephritis has been
observed later in the course of snakebite regardless of anti-
venom administration.9,20 There is deposition of C3 and IgM
in the glomerular mesangium.20 The evidence suggests an
immune complex glomerulonephritis with implanted anti-
gen, followed by IgM deposit acquired naturally. Alterna-
tively, this could be due to a concealed infection in the
snakebite that results in immune complex glomerulonephri-
tis with predominant deposition of IgM and C3 in the
mesangial areas. At present, the evidence is in favour of
glomerulonephritis directly induced by the snake venom.
The immunological role is rather weak but cannot be
entirely denied, especially the role of immune complex in
situ. Further studies in animals are required.
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Journal compilation © 2006 Asian Pacific Society of Nephrology