Biology Reference
In-Depth Information
observed in these envenomations (
Figure 4.4
). Although the AKI and chronic renal
dysfunction may be largely due to these proposed mechanisms, there is a strong pos-
sibility of a direct nephrotoxin in some of these venoms as have been detected in ven-
oms of other colubroids. For example, direct nephrotoxicity of
D. russelii
venom has
been demonstrated in the perfused rat kidney (Ratcliffe et al., 1989). A basic 7.2-kDa
nephrotoxin has been isolated from
D. r. russelii
venom (Mandel and Bhattachuryya,
2007). The authors suggested that this toxin (“RVV-7”) was renally concentrated and
its accumulation resulted in necrotic destruction of the tubular epithelium (Mandel and
Bhattachuryya, 2007). A recent review suggested that renal cell-adhesion molecules
(cadherins, catenins, etc.) may be important early targets for nephrotoxic venom com-
ponents (Prozialeck and Edwards, 2007).
AKI from venom-induced consumptive coagulopathy/DIC should be managed ini-
tially by the early administration of specific antivenom if available, and careful fluid
resuscitation (with adjustment for any individual comorbidities, e.g., congestive heart
failure). Some medications used for renal protection under certain circumstances (e.g.,
during provision of contrast media) such as
N
-acetylcysteine may be considered on
a case-by-case basis. However, the putative protective effects of medications such as
N
-acetylcysteine are unclear and unproven when used in the setting of AKI caused by
different ischemia-related etiologies (e.g., elective aortic aneurysm repair; Macedo
et al., 2006). There are no trialed, tested, or well-documented data regarding the use
of
n
-acetylcysteine or other renally protective medications in management of coagu-
lopathic envenoming. The use of angiotensin-converting enzyme inhibitors (ACEI) in
these cases is worthy of study, although ACEI can precipitate AKI in some patients,
and there is a report suggesting ACEI exacerbation of venom-induced hypotension
(Svensson et al., 1993). Emerging data also suggest a potential protective role in LPS-
induced AKI of protein C due to its modulatory effects on renal inflammation. This
includes downregulation of renal inducible nitric oxide synthase and reduction of the
mRNA expression involving the renin-angiotensin system, renal ACE-1 as well as
angiotensin II (Gupta et al., 2007). The possible therapeutic application of activated
protein C in coagulopathic envenoming such as those from hazard level 1 colubrids
may be worthy of careful investigation.
Additional management should follow standard protocol and include careful
placement of a Foley catheter in order to closely monitor diuresis (being mindful of
concomitant coagulopathy-related risks in such a procedure); serial assessment of elec-
trolytes and treatment of hyperkalemia as indicated; judicious use of loop diuretics
along with careful hydration (choice of i.v. fluid is at the discretion of the attending
physician); provision of oral and i.v. amino acids and oral fluids (volume of urinary
output
500 mL/day); and increased carbohydrate intake in order to minimize catabo-
lism. Nephrology consultation is strongly recommended. Dialysis should be performed
as necessary, although, as noted, response is often suboptimal in serious cases. Some
studies have suggested that hemodialysis has a more favorable outcome in venom-
induced AKI than peritoneal dialysis (Wiwanitkit, 2005), although the choice of the
method used may be governed by availability. Patients should be counseled regarding
the potential for loss of function despite correct therapy, as well as the possibility of
extended need for dialysis and/or additional supportive measures.
