JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC #1901151): Beagle dog
HISTORY: Tissue from a 2-year-old female beagle dog used as a control in an inhalation toxicity study, and the histopathological changes were an incidental finding
HISTOPATHOLOGIC DESCRIPTION: Kidney: Multifocally, approximately 20% of glomeruli are variably and segmentally distorted and glomerular capillary lumina are compressed, expanded or obliterated by large, densely-packed foam cells within the mesangium which are up to 40 um in diameter with cytoplasm containing fine, clear microvacuoles with variably sized eosinophilic globules and granules. Foam cell nuclei are often pyknotic, and peripherally compressed. Occasionally, foam cells contain fine golden-yellow granules (lipofuscin). In the cortex, tubules are rarely mildly dilated, lined by attenuated epithelium, and filled with a homogenous, eosinophilic, hyalinized material (proteinosis). Tubules within the medulla rarely contain small deeply basophilic granular material (mineral).
MORPHOLOGIC DIAGNOSIS: Kidney, glomeruli: Vacuolar change, lipid-type, segmental, multifocal, moderate, with mesangial foam cells, beagle, canine
ETIOLOGIC DIAGNOSIS: Glomerular lipidosis
- Glomerular lipidosis (GL) is characterized by accumulation of foam cells within dilated the glomerular tuft
- Recent studies suggest that GL is likely not an incidental finding as previously described
- GL has rarely been the sole identified lesion in dogs with marked hypoproteinemia as well as experimental injection of biologic toxins (snake venom and diphtheria toxin)
- Dogs with severe GL tend to be younger than those with mild GL
- Glomerular foam cell accumulation differs from foam cell and lipid accumulation in the renal interstitium and likely has a different pathogenesis
- This is a separate entity from lipid embolization that may occur in animal with diabetes mellitus or dyslipidemia (see differential diagnoses below)
- The pathogenesis of glomerular foam cell accumulation is unknown and likely multifactorial
- It is theorized that initial podocyte injury leads to disordered lipid metabolism with endothelial and mesangial production of pro-inflammatory cytokines that recruit macrophages and foam cells to the site of injury
- Cell or origin has also been proposed as mesangial or endothelial cell
- GL is noted as a concurrent lesion with several types of glomerular disease including focal segmental glomerulosclerosis (FSGN; most common), juvenile nephropathy, and glomerular amyloidosis
- GL is typically mild in dogs with FSGN
- Severe lesions are most often present in dogs with GL as the sole diagnosis and in dogs with concurrent juvenile nephropathy
- Glomerular foam cells were a rare finding in a recent case series of miniature Schnauzer dogs with idiopathic hypertriglyceridemia and Shetland sheepdogs with hypercholesterolemia
- Glomerular lipid emboli (GLE) was a more common finding in the miniature schnauzer study
- GL is distinct from GLE due to the absence of lipid laden foam cells in GLE
- Does not appear to be associated with immune complex-mediated glomerulonephritis
TYPICAL CLINICAL FINDINGS:
- May be associated with proteinuric renal disease, hypertension, azotemia, and hypoalbuminemia
- May be associated with hypertriglyceridemia and hypercholesterolemia
TYPICAL GROSS FINDINGS:
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Foam cells – large, up to 40 um, closely packed,lipid containing cells with clear microvacuoles and indistinct cell borders within glomerular mesangium and may compress adjacent glomerular capillaries
- Multiple glomeruli may be involved and there is also dilation of capillary loops; there may be lipid laden cells in capillaries in addition to the mesangium, and there may be mesangiolysis
- Mesangial cells contain intracytoplasmic lipid globules
- Endothelial cells have intracytoplasmic vacuolation and globular inclusions
ADDITIONAL DIAGNOSTIC TESTS:
- Sudan black special stain for lipid; droplets within foam cells are sudanophilic
- Lipid emboli – may occur following trauma or in acute pancreatitis or diabetes mellitus, nutritional panniculitis in horses (“yellow fat disease”); lipid is present in arterioles and glomerular capillaries, not in foam cells
- Two proposed mechanisms: 1) direct entry of fat emboli into the bloodstream after trauma; 2) generation of fat emboli from plasma lipoprotein disruption exceeding the capacity of incorporation into lipoproteins and coalescence of lipid at the intravascular gas bubble interface
- Spontaneous glomerular lipidosis reported in APA strain
- Hyperlipidemic mice crossed with podocyte depleted mice developed significant podocyte loss in glomeruli affected by GL in a recent study
- Inherited hyperlipoproteinemia in cats causes an extensive glomerular lipidosis with increased mesangium and a thickened Bowman’s capsule, and hyperchylomicronemia, atherosclerosis, and xanthogranulomas in numerous visceral organs
- Interstitial lipid accumulation occurs in cats with chronic kidney disease (CKD) and may be related to tubular lipidosis (typical in cats) and is associated with epithelial degeneration and lysis, and tubular basement membrane fragmentation
- Interstitial lipid accumulation is only observed in the renal cortex in cats with CKD
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- Martino-Costa AL, Malhao F, et al. Renal interstitial lipid accumulation in cats with chronic kidney disease. J Comp Pathol. 2017; 157:75-79.
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- Suárez-Bonnet A, Espinosa de los Monteros A, Herráez P, Rodríguez F, Andrada M, Caballero MJ. Fat embolism secondary to yellow fat disease in an Appaloosa horse. J Vet Diagn Invest. 2008 Sep; 20(5):684-7.