Vitamin E therapy in IgA nephropathy: a double-blind, placebo-controlled study

Abstract

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127+/-50 vs. 112+/-31 ml/min/1.73 m(2), respectively ( P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24+/-0.38 vs. 0.61+/-1.37 ( P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.

Nutritional and Safety Outcomes from an Open-Label Micronutrient Intervention for Pediatric Bipolar Spectrum Disorders

“…A U-shaped dose response curve may exist for the anti-inflammatory effects of c-TC, with implications for safety (McCary et al 2011). The dose of a-TC in EMP + as recommended (360 IU total from 15 capsules per day) is lower than that shown to be safe and effective in a small RCT in children with immunoglobulin (Ig)A nephropathy (400 or 800 IU/day, respectively for body weights of <30 kg or >30 kg; Chan et al 2003), but significantly more than the United States RDA (http://ods.od.nih.gov/ factsheets/VitaminE-HealthProfessional/ ). Concern about differential responses to vitamin E supplementation in children versus adults and healthy versus chronic disease status exists.…”

Modulating the Progression in IgA Nephropathy

“…Finally, in a randomized, double-blinded study in children with biopsy-proven IgA nephropathy, Chan et al [31] demonstrated that vitamin E significantly reduced proteinuria. While there was a trend to stabilization of glomerular filtration rate in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function.…”

“…Thus proliferation of human mesangial cells and production of immune/chemical mediators and superoxide anions may be amplified by nephritogenic IgA-IC, resulting in kidney lesions commonly seen in IgA nephropathy [26]. The increased production of superoxide anions by kidney mesangial cells [27] and polymorphonuclear leukocytes [26] support a novel direction in the treatment of IgA nephropathy, namely the use of an antioxidant, such as vitamin E, to prevent mesangial cell proliferation and attenuate growth-factor-mediated kidney injury [30, 31]. In parallel with enhanced superoxide production, aggregated IgA induces Fcα receptor expression in leukocytes [27, 32].…”

Antioxidant Capacity of 55 Medicinal Herbs Traditionally Used to Treat The Urinary System: A Comparison Using A Sequential Three-Solvent Extraction Process

“…1 Oxidative damage is thought to be a major mechanism involved in the development of numerous renal disorders including diabetic nephropathy, 2 ischemic nephropathy, 3 some types of iatrogenic nephropathy, 4,5 Balkan endemic nephropathy, 4 IgA nephropathy, 6 and others. 7 As the renal condition worsens and the patient enters chronic renal failure, the resulting uremia leads to systemic oxidative stress and damage to other organs.…”