Renal lesions in rhabdomyolysis caused by Pseudechis australis snake myotoxin

Abstract

The renal lesions at various time intervals after i.m. injection of Pseudechis australis myotoxin (PA myotoxin) causing myoglobinuria in mice was studied. Biochemical assay of serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) showed marked elevations [7166 ± 2064 IU and 1626 ± 211 Berger-Broida U/ml (B-B U/ml)] six hours after injection, indicative of rhabdomyolysis. Serum creatinine (1.6 ± 0.39) and urea (147 ± 40) showed significant rise by 48 hours indicative of acute renal failure (ARF). Immunodiffusion showed the presence of myoglobin in the urine (myoglobinuria) of experimental animals. Light microscopic (LM) and scanning electron microscopic (SEM) studies of the urinary sediments from experimental mice revealed granular casts of varying size and shape. LM of kidney showed casts from one hour and tubulopathy with degenerated tubular epithelial cell from 12 hours onwards. Focal glomerular changes, such as dilated Bowman's space with poorly stained substance and reduction in number of glomerular tufts were observed. Immunofluorescence microscopy for myoglobin showed fluorescence of the casts in the tubules. Transmission electron microscopy (TEM) showed electron dense casts occupying the entire lumen of the distal convoluted tubules (DCT). The proximal convoluted tubules (PCT) showed features of proximal tubular necrosis (PTN). There was reduction in the basal infolding with activation of lysosomal system in the PCT. The glomeruli showed changes in the visceral epithelium that included intracellular edema, vesiculation and occasional fusion of the podocytes. Numerous granular materials were observed in the Bowman's space as well as in the lumen of the capillaries from 1 to 24 hours. Electron dense deposits of the glomerular basement membrane (GEM) capillaries were observed from 1 to 24 hours. SEM study revealed loss of microvilli of the PCT and some tubular lumen were filled with cast like material. Some glomeruli displayed a relatively flattened podocytes with thickened major foot processes. Regeneration of the tubules were seen from three weeks onwards.