Biology Reference
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controversial, it is probable that risk of end-stage renal disease is greater in those who
have had a renal insult requiring dialysis. This must be considered in the long-term
prognosis of patients who have experienced ARF requiring dialysis from coagulopathic
envenoming, including those from hazard level 1 colubrids.
Experimental pathophysiological study of venom-induced AKI has provided some
correlation between renal pathology in the rat model and clinical manifestations in
envenomed humans. Glomerular, tubular, interstitial, and vascular lesions have been
described. Experimentally, some venoms (e.g., from viperids) cause mesangiolysis,
and this may be a significant factor in the pathogenesis of some venom-induced glo-
merular disease (George et al., 1987). Burdmann et al. (1993) studied ARF induced
in rats by i.v. injection of
B. jararaca
(jararaca) venom. Noted were acutely decreased
glomerular filtration rate, diuresis and renal plasma flow; intravascular hemolysis;
and hypofibrinogenemia. Histopathology revealed massive fibrin deposition in glo-
merular capillaries, proximal and distal tubular necrosis, and tubular deposition of
erythrocyte casts (Burdmann et al., 1993). The authors emphasized ischemia due
to glomerular coagulation and intravascular hemolysis as the most important fac-
tors influencing renal damage. Direct venom nephrotoxicity could not be excluded,
as has been noted by other authors who have reported that some venom-induced
renal lesions appear to reflect a direct action of venom toxins on kidney parenchyma
(George et al., 1987; Burdmann et al., 1993). These findings resemble those deter-
mined from renal biopsy performed in patients with AKI caused by severe enven-
oming from
D. typus
or
R. tigrinus
(Lakier et al., 1969; Mittleman and Goris, 1978;
Nakayama et al., 1973).
Generally, available data suggest the following basic mechanisms of consump-
tive coagulopathic envenoming-induced AKI: generation of microthrombi, develop-
ment of hypofibrinogenemia, anemia (probably mainly due to hemolysis and splenic
clearance of schistocytes, etc.), and intravascular hemolysis. Some of these processes
cause a rapid deposition of hemoglobin and erythrocyte casts in the renal tubules and
result in acute tubular necrosis. Simultaneously, microthrombi accumulate in glomer-
uli, and probably in the afferent and efferent vasculature. Additionally, it is likely that
the decreasing erythrocyte population causes increased stimulation of the peritubular
and/or tubular capillary endothelial cells to produce erythropoietin in order to replen-
ish the sudden drop in erythrocytes and restore the concomitantly decreased transport
of oxygen. The oxygen deficiency could also stimulate the rate of adenosine forma-
tion, thereby lowering the rate of glomerular filtration by constriction of afferent arteri-
oles, particularly in superficial nephrons, thus lowering the salt load and renal transport
workload (Vallon and Osswald, 2009). Likewise, in response to hemorrhage and con-
comitant hypotensive effects, renin secretion from the juxtaglomerular cells (as well
as other recruited renal cells in the circumstance of a growing threat to homeostasis)
will predictably increase. These simultaneous processes will likely exert greater met-
abolic stress on renal function within a developing ischemic state. It is possible that
this may stimulate acute tubular apoptosis as opposed to strictly defined acute tubular
necrosis, as has been suggested for mechanisms contributing to Gram-negative, sepsis-
induced renal failure (Wan et al., 2003). Therefore, dynamic and progressive combina-
tions of prerenal and intrarenal pathophysiological processes comprise the renal effects
