Role of lipids in the progression of renal disease in systemic lupus erythematosus patients.
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.
Luzar
B
B
Institute of Pathology, Faculty of Medicine University of Ljubljana, Slovenia. luzar@ibmi.mf.uni-lj.si
Ferluga
D
D
D000328:Adult; D018450:Disease Progression; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006977:Hypertension, Renal / Q000209:etiology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D050356:Lipid Metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D009404:Nephrotic Syndrome / Q000209:etiology; D012008:Recurrence; D016896:Treatment Outcome