Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation

Abstract

Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation.

Acute Kidney Injury Secondary to Lonomia envenomation. Case Report and Literature Review

“…A renal puncture with biopsy was performed in one of the reported cases and on one of the patients included in the cohort study. It showed acute tubular necrosis with mesangial proliferative glomerulonephritis and mononuclear interstitial infiltrates (9), and only signs of acute tubular necrosis (3), respectively, which supports the previous approach.…”

“…Since the kidney is a highly vascularized organ whose function is to filter and excrete waste, including venom, it is very susceptible to toxins, with a variable spectrum of manifestations ranging from interstitial tubule nephritis, passing through glomerulonephritis, vasculitis, tubulointerstitial nephritis and acute tubular necrosis, the latter being the most frequent (13). Envenomation with this species causes what is known as severe hemorrhagic syndrome, which has clinical manifestations such as coagulation alterations, ecchymosis, acute kidney failure and generalized hemorrhage (2,9,13,14). The components with pro-coagulant, fibrinogenolytic, proteolytic and hemolytic activity cause a condition compatible with disseminated intravascular coagulation associated with a consumption coagulopathy, caused by a plasminogen activator, an enzyme similar to plasmin, two proteases that act on factor V and another on factor XIII, generating an activation in the fibrinolytic cascade that can mask the latter (4,15), which are one of the mechanisms that cause kidney damage (14,16,17) by forming microthrombi in the kidney microcirculation and generating a state of hypoxia and tissue ischemia that alters its functioning and causes cell death (6,3,14).…”

“…A kidney function test and a partial urinalysis should be performed, as in this case hematuria is a clinical manifestation of an intrinsic kidney disorder that is associated with the development of acute tubular necrosis in some patients, which is the basis of acute kidney failure, and therefore of the development of an unsatisfactory systemic state with high mortality rates; this factor alerts to the need of establishing a fast and effective therapeutic plan (9,28,36,37). The diagnosis of acute kidney failure was made in a study by Gambordi et al…”

“…Similarly, patients with acute kidney failure as a manifestation of nephrotoxicity from the larva have hemodynamic and systemic repercussions that can quickly lead to multiorgan dysfunction (9,36). Intravascular hemolysis is a rare complication that has been observed only in the most severe cases of this pathology, associated with contact with a large number of caterpillars, and as well as the two aforementioned entities, it also has a worse prognosis in those patients who present them (43,44).…”

Molecular Characterization of Three Novel Phospholipase A2 Proteins from the Venom of Atheris chlorechis, Atheris nitschei and Atheris squamigera

“…The higher-order catalytic hydrolysis functions of these snake enzymes play a central role in lipid metabolism of numerous cells and tissues, contributing to prey digestion. In addition, much is known about the wide variety of pathological effects exhibited by the snake venom phospholipase A 2 s including their neurotoxicity, myotoxicity, cytotoxicity, anticoagulant effects, cardiotoxicity, hypotension induction, platelet aggregation/inhibition and anti-bacterial activities [ 5 , 6 , 7 , 8 , 9 , 10 ], which in many cases, are fundamental to the toxicity of snake venoms [ 11 , 12 ].…”