Role of lipids in the progression of renal disease in systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disea se marked by immune-complex mediated lesions in small blood vessels of vari ous organs, especially the kidneys, although other factors may also be impl icated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstiti al 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 glomeru lonephritis, progressively active in the first patient, severe nephrotic-ra nge persistent proteinuria, arterial hypertension associated with hyperfilt ration and hyperperfusion injuries and, to a minor extent, hyper- and dysli pidemia were observed. Immunological and non-immunological factors were sho wn to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstit ial lipid deposits were probably causally related to both hyperlipidemia an d the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as smal l cleft-like spaces found to be impacted in the tubular lumina. They were s een to penetrate tubular epithelial cells and eventually lodge in the inter stitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune depo sits 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 lipid s and calcium precipitates, suggesting a peripheral atherosclerosis-like pr ocess 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. Associat ed either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltr ation, or tubulo-interstitial lipid deposition, the mechanism of tissue dam age by lipids in all parts of the nephron shares similarities with the path ogenesis of systemic atherosclerosis.