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Publication
Hydroxypropyl-ß-cyclodextrin protects from kidney disease in experimental Alport
syndrome and focal segmental glomerulosclerosis.
Authors Mitrofanova A, Molina J, Varona Santos J, Guzman J, Morales XA, Ducasa GM, Bryn
J, Sloan A, Volosenco I, Kim JJ, Ge M, Mallela SK, Kretzler M, Eddy S, Martini
S, Wahl P, Pastori S, Mendez AJ, Burke GW, Merscher S, Fornoni A
Submitted By Submitted Externally on 12/12/2018
Status Published
Journal Kidney international
Year 2018
Date Published 12/1/2018
Volume : Pages 94 : 1151 - 1159
PubMed Reference 30301568
Abstract Studies suggest that altered renal lipid metabolism plays a role in the
pathogenesis of diabetic kidney disease and that genetic or pharmacological
induction of cholesterol efflux protects from the development of diabetic kidney
disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether
altered lipid metabolism contributes to renal failure in the Col4a3 knockout
mouse model for Alport Syndrome. There was an eight-fold increase in the
cholesterol content in renal cortexes of mice with Alport Syndrome. This was
associated with increased glomerular lipid droplets and cholesterol crystals.
Treatment of mice with Alport Syndrome with hydroxypropyl-ß-cyclodextrin (HPßCD)
reduced cholesterol content in the kidneys of mice with Alport Syndrome and
protected from the development of albuminuria, renal failure, inflammation and
tubulointerstitial fibrosis. Cholesterol efflux and trafficking-related genes
were primarily affected in mice with Alport Syndrome and were differentially
regulated in the kidney cortex and isolated glomeruli. HPßCD also protected from
proteinuria and mesangial expansion in a second model of non-metabolic kidney
disease, adriamycin-induced nephropathy. Consistent with our experimental
findings, microarray analysis confirmed dysregulation of several lipid-related
genes in glomeruli isolated from kidney biopsies of patients with primary FSGS
enrolled in the NEPTUNE study. Thus, lipid dysmetabolism occurs in non-metabolic
glomerular disorders such as Alport Syndrome and FSGS, and HPßCD improves renal
function in experimental Alport Syndrome and FSGS.




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