Vitamin E Ameliorates Renal Injury in an Experimental Model of Immunoglobulin A Nephropathy1

Abstract

IgA nephropathy is one of the most common forms of glomerular disease. Nearly 25% of affected patients progress to end-stage renal disease over a 20-25-y follow-up period. IgA-containing immune complexes stimulate oxygen-free radical production by mesangial cells in vitro. The excessive oxidant stress may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal disease in an experimental model of incipient IgA nephropathy with mild kidney inflammation. IgA nephropathy was induced in male Lewis rats by oral immunization with 0.1% bovine gamma-globulin (BGG)-containing drinking water for 8 wk. At the completion of this period, animals received BGG, 1 mg/dose i.v., on three successive days. Experimental rats (n = 10) received a specially formulated diet containing 100 IU of vitamin E/kg of chow, whereas control animals (n = 10) were fed chow containing 30 IU of vitamin/kg of chow. The BGG immunization regimen induced mesangial IgA deposition in all rats. Vitamin E supplementation resulted in a nearly 5-fold increase in the serum vitamin E concentration. Vitamin E-treated rats gained more weight and had a lower incidence of hematuria, 20% versus 80% (p < 0.03). Moreover, proteinuria was decreased by 50%, and reduced renal plasma flow was restored to normal, compared with untreated rats with IgA nephropathy. Glomerular hypertrophy occurred in animals with IgA nephropathy, but less so in those receiving vitamin E supplementation. Renal cortical malondialdehyde content was reduced from 1.55 +/- 0.10 to 1.22 +/- 0.09 nmol/mg of protein (p < 0.01) in rats fed the vitamin E-enriched diet. Finally, renal transforming growth factor-beta 1 gene expression was reduced by 34% in rats with IgA nephropathy receiving vitamin E treatment (p < 0.05). We conclude that experimental IgA nephropathy is associated with increased renal oxidant injury. Dietary treatment with the antioxidant agent, vitamin E, attenuated renal functional and structural changes in this experimental glomerulopathy. These studies support the importance of clinical trials for the evaluation of the efficacy of antioxidant therapy in patients with IgA nephropathy.

Modulating the Progression in IgA Nephropathy

“…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].…”

“…Increased renal expression of TGF-β1 has been associated with severity of kidney disease in models of IgA nephropathy in rats [30]. The finding of elevated intrarenal levels of glomerular TGF-β1 mRNA has been reported in patients with IgA nephropathy [58].…”

Chronic Renal Failure: An Overview from a Pediatric Perspective

“…Working with an experimental IgA nephropathy rat model, Trachtman et al [183]have shown increased free radical release. They demonstrated that vitamin E can reduce the incidence of hematuria and the degree of proteinuria and ameliorate the elevated TGF-β1 levels.…”

Protective effects of tubular liver-type fatty acid-binding protein against glomerular damage in murine IgA nephropathy

“…Recently, Kobori and co-workers [11] also found augmentation of intra-renal oxidative stress at early stages of IgAN, and that the activated intra-renal ROS played some roles in the development of IgAN by interacting with activated RAS. Trachtman et al [40] showed that dietary treatment with antioxidant agent-vitamin E attenuated renal functional and structural changes in the experimental IgAN model. Kuemmerle et al [41] also reported that administration of alpha tocopherol ameliorated renal injury in a rat experimental model of IgAN.…”