Liposoluble vitamins A and E in kidney disease

Table 1 Postulated mechanisms of action of retinoid administration in animal models of kidney disease and reported human clinical trials

Drug	Animal model/disease/n		Outcome
Animal
atRA	anti-Thy1.1 model rats	Mesangioproliferative glomerulonephritis	RA limits glomerular proliferation, glomerular lesions, and albuminuria. Marked reduction in renal TGF-β1. Reduction RAS activity[29]
atRA	HIV-1–transgenic mice	HIV associated kidney disease	atRA inhibits proliferation and induces differentiation in podocytes through RAR-mediated cAMP/PKA activation[28]
atRA	Streptozotocin-induced diabetic rats	Diabetic kidney disease	atRA decreases MCP-1 urinary excretion. Decreases proteinuria[34]
Tamibarotene	Male C57BL/6 mice	Unilateral ureteral obstruction	Inhibits the accumulation of fibrocytes and alleviates renal fibrosis mediated by IL-17A[64]
atRA	Atg5flox/flox:Cagg-Cre mice	Cisplatin nephrotoxicity	RA activates autophagy and alleviates cisplatin acute kidney injury[37]
atRA	Male rats	Unilateral ureteral obstruction	ATRA treatment can increase the angiopoitin-1 and decrease interstitial fibrosis[65]
Human
Isotretinoin	FSGS; MCD (shase II study)	12 (only 6 completed the study)	No complete or partial remission at 6 mo (clinicaltrials.gov)
Tamibarotene	Lupus nephritis (phase II study)	20	Not published

atRA: All-trans-retinoic acid; MCP-1: Monocyte chemoattractant peptide; FGFS: Focal segmental glomerulosclerosis; MCD: Minimal change disease; TGF-β1: Transforming growth factor-β1; HIV: Human immunodeficiency virus; RA: Retinoic acid; IL: Interleukin.

Table 2 Reported human clinical trials of vitamin E administration in chronic kidney disease subjects

Ref.	n	Dose	Inclusion criteria	Outcome
Mann et al[49]	993	400 IU/d	1.4 ≤ SCr ≤ 2.3 mg/dL. Plus CV disease or DM	Follow-up 4.5 yr. No apparent effect on CV outcomes
Giannini et al[50]	10	1200 IU/d	Type 1 diabetes mellitus plus macroalbuminuria	Reduces markers of oxidative stress. No effect on MA
Khatami et al[51]	60	1200 IU/d	Diabetic nephropathy	Decrease in protein/creatinine ratio. Reduction in inflammatory markers
Boaz et al[52]	196	800 IU/d	Hemodialysis patients	Reduces CV disease
Himmelfarb et al[53]	30	300 IU/d	15 healthy subjects, 15 hemodialysis patients	Reduction on C reactive protein
Bergin et al[54]			Meta-analysis 16 papers	Reduction oxidative stress
Mune et al[55]	40	300 mg/d	Hemodialysis subjects	Improvement in endothelial function

CV: Cardiovascular.