Diabetic Nephropathy - Treatment

Vitamin C - updated: 15 March 2008

Blockade of oxidative stress by vitamin C ameliorates albuminuria and renal sclerosis in experimental diabetic rats Blockade of oxidative stress by vitamin C ameliorates albuminuria and renal sclerosis in experimental diabetic rats

Yonsei Med J. 2007 Oct 31;48(5):847-55

Lee EY, Lee MY, Hong SW, Chung CH, Hong SY.

PURPOSE: Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney. MATERIALS AND METHODS: Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n=8) and a vitamin C-treated group (n=8). Long-Evans Tokushima Otsuka rats (n=8) were used as a control. RESULTS: Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats. CONCLUSION: By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy.

Publication Types:

• Animal Study

Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes

J Am Soc Nephrol. 1997 Sep;8(9):1405-14

Craven PA, DeRubertis FR, Kagan VE, Melhem M, Studer RK.

Oxidant stress and a reduction in antioxidant status, including reduced plasma and tissue ascorbic acid content, occur in diabetic patients and experimental models of diabetes. In this study, the effects of treatment of streptozotocin diabetic rats for 2 mo with vitamin C (10 g/kg body wt/d) or dietary vitamin E (200 mg/kg body wt/d) in the drinking water on urinary albumin excretion, glomerular transforming growth factor (TGF)-beta content, and glomerular size were examined. Treatment of diabetic rats with vitamin C or E had no effect on blood glucose levels compared with that in untreated diabetics (453 +/- 28 g/dl +/- SEM). Body weight, BP, and creatinine clearance rates were not significantly different among the study groups. Kidney weight was significantly higher in all of the diabetic groups compared with age-matched control rats. Treatment with vitamin C, but not vitamin E, significantly reduced kidney weight compared with that in untreated diabetic rats. Immunohistochemical staining for TGF-beta was 2.5-fold higher in glomeruli of cortical sections from untreated diabetic rats versus control rats. Treatment with vitamin C or E prevented the increase in glomerular TGF-beta immunoreactivity. Glomerular volume was also significantly increased (twofold) in kidneys of untreated diabetic rats compared with control rats, as assessed by light microscopy. Treatment with vitamin C prevented and treatment with vitamin E reduced the increase in glomerular volume. Treatment with vitamin C also prevented the sevenfold increase in albumin clearance otherwise seen in untreated diabetic rats. By contrast, treatment with vitamin E had no effect on albumin clearance despite reductions in glomerular size and TGF-beta. Renal cortical vitamin E and plasma, but not renal cortical vitamin C, were reduced in diabetic rats versus control rats. Supplementation of diabetic rats with vitamin C markedly increased plasma and renal cortical vitamin C content to values greater than those in control rats. Supplementation with vitamin E increased renal cortical vitamin E content by 50% compared with values in control rats and also increased plasma and renal cortical vitamin C. These results support the potential utility of antioxidant treatment for the prevention of renal injury in diabetes.

Publication Types:

• Animal Study

Effect of vitamin E and vitamin C supplementation on antioxidative state and renal glomerular basement membrane thickness in diabetic kidney

Nephron Exp Nephrol. 2003;95(4):e134-43

Kedziora-Kornatowska K, Szram S, Kornatowski T, Szadujkis-Szadurski L, Kedziora J, Bartosz G.

The aim of this study was to analyze the effect of vitamins C and E on malondialdehyde (MDA) content and activities of key antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as glomerular basement membrane (GBM) thickness in streptozotocin-induced diabetic kidney in rats. Wistar male rats were divided into following groups (12 rats each): the control, diabetic rats, diabetic rats whose drinking water was supplemented with vitamin C in a dose of 1.0 g/l or diet was supplemented with 200 mg of vitamin E/100 g fodder. Body weight, blood glucose and HbA1C levels and 24-hour urinary albumin excretion (UAE) were studied every week (0-12 weeks). After 6 and 12 weeks, MDA content and activities of SOD, CAT and GSH-Px were measured in the kidney homogenate supernatants. Electron micrographs of glomeruli were scanned and morphometric investigations were performed by means of computer image analysis system to compare GBM thickness. The blood glucose and HbA1C concentrations and UAE in diabetic rats were significantly higher than in the control group. An increase in the MDA level and decrease in the SOD, CAT and GSH-Px activities in the kidney of diabetic rats were observed after 6 and 12 weeks of experiment. Administration of vitamins C and E did not affect body weight, blood glucose and HbA1C levels. Both vitamin C and vitamin E decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats as well as reduced UAE, decreased kidney weight and GBM thickness. The results indicate the potential utility of antioxidant vitamins in the protection against the development of diabetic nephropathy.

Publication Types:

• Animal Study

Serum Vitamin C Levels in Type 2 Diabetic Nephropathy

Diabetes Care 28:2808-2809, 2

Kenzo Iino, MD, Takuko Fukui, MD, Keizo Anzai, MD, Masanori Iwase, MD, Kazuhiko Kogawa, MD, Masaro Ogimoto, MD, Junko Ono, MD, Takashi Asano, MD, Mitsuo Iida, MD and Kazuo Tamura, MD

Serum vitamin C concentrations have been reported to be low in diabetic patients. Diabetic nephropathy is known to develop in diabetic individuals, and decreased renal function and hypertension could reportedly accelerate atherosclerosis in patients with type 2 diabetes. Observational epidemiologic studies showed an inverse relation between the dietary intake or serum levels of vitamin C and blood pressure. Although reduced concentrations of vitamin C were reported in type 2 diabetic retinopathy, the concentrations of serum vitamin C in type 2 diabetic patients with diabetic nephropathy have not been previously reported. The aim of the present study is to determine whether the concentrations of serum vitamin C have any relation to type 2 diabetic nephropathy. Since diabetic nephropathy is associated with low-grade inflammation, we also examined the inflammatory marker of high-sensitivity C-reactive protein (hs-CRP).

Moderate exercise combined with dietary vitamins C and E counteracts oxidative stress in the kidney and lens of streptozotocin-induced diabetic-rat

Int J Vitam Nutr Res. 2005 Jan;75(1):71-

Kutlu M, Naziro?lu M, Sim?ek H, Yilmaz T, Sahap Kükner A.

Oxidative stress has a key role in the pathogenesis of diabetes-induced cataract formation and nephropathy. Daily moderate exercise and vitamins C and E (VCE) supplementation can be beneficial to diabetes due to reducing blood glucose and free radical production. The aim of this study was to analyze the effect of moderate exercise with vitamin VCE on lipid peroxidation (LP) and antioxidative systems in the kidneys and lens of streptozotocin-induced diabetic rats. Forty female Wistar rats were used. They were randomly divided into four groups. The first and second groups were used as control and diabetic groups. The third group was the diabetic-exercise group. VCE-supplemented feed was given to diabetic-exercise rats constituting the fourth group. Animals in the exercised groups were moderately exercised daily on a treadmill for three weeks (five days a week). Diabetes was induced on day zero of exercise. Body weights in the four groups were recorded weekly. Lens and kidney samples were taken from all animals on day 20. Glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in kidney and lens, albumin in plasma, and body weight were significantly lower in the diabetic group than in the control group, whereas there was a significant increase in LP of kidney and lens as well as plasma glucose, urea, and creatinine levels in the diabetic group. The decrease in antioxidant enzymes, vitamins, and albumin and the increase in LP and glucose levels in diabetic rats were significantly improved with exercise and VCE supplementation. In the diabetic animals, the decreased beta-carotene and vitamins A levels in kidney did not improve through exercise only, although their levels were increased by exercise plus VCE supplementation. In conclusion, these data demonstrate that lipid peroxidation increases in the lens and kidney of diabetic animals and this could be due to decreases in antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system through the reduction of ROS and blood glucose levels. The VCE supplementations with exercise may play a role in preventing the development of diabetic nephropathy and cataract formation in diabetic animals.

Publication Types:

• Animal Study

Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes

Diabetes Care. 2005 Oct;28(10):2458-64

Farvid MS, Jalali M, Siassi F, Hosseini M.

OBJECTIVE: The present study was designed to assess the effect of magnesium plus zinc, vitamins C plus E, and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months: group M (n = 16), 200 mg Mg and 30 mg Zn; group V (n = 18), 200 mg vitamin C and 100 IU vitamin E; group MV (n = 17), minerals plus vitamins; and group P (n = 18), placebo. Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity (NAG) in urine were determined at the beginning and at the end of the trial. Treatment effects were analyzed by general linear modeling. RESULTS: Results indicate that after 3 months of supplementation, levels of urinary albumin excretion decreased in the V and MV groups (P = 0.034 and P = 0.005, respectively). Urinary NAG activity did not significantly change in any treatment groups. Levels of systolic, diastolic, and mean blood pressure significantly decreased in the MV group (P = 0.008, P = 0.017, and P = 0.009, respectively). Also, combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose (P = 0.035) and malondialdehyde concentrations (P = 0.004) and in increasing HDL cholesterol and apolipoprotein A1 levels (P = 0.019). There was no significant change in the levels of these parameters in the other three groups. CONCLUSIONS: In conclusion, the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium, zinc, and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients.

Publication Types:

• Placebo Controlled

Ascorbic acid clearance in diabetic nephropathy

J Diabetes Complications. 1998 Sep-Oct;12(5):259-63

Hirsch IB, Atchley DH, Tsai E, Labbé RF, Chait A.

The incidence of cardiovascular disease is increased in diabetic nephropathy. Increased oxidative stress in diabetes is believed to play an important role in the pathogenesis of atherosclerosis in diabetes. Since antioxidant vitamins, such as ascorbic acid, often are reduced in diabetes, we hypothesized that the renal clearance of ascorbic acid is increased in patients with diabetic nephropathy. Thirty-seven subjects with diabetic nephropathy were studies: 18 had microalbuminuria (30-300 mg/day albuminuria); the remainder had clinical nephropathy (> 300 mg/day albuminuria). Indices of glycemic control (glucose, hemoglobin A1C) and renal function (albuminuria and creatinine clearance) were measured in addition to serum and urinary ascorbic acid levels. Results showed that subjects with clinical nephropathy had lower mean plasma ascorbic acid (p=0.0009) and higher renal clearance of ascorbic acid (p=0.005) than those with microalbuminuria. Bivariate analysis revealed an inverse correlation between creatinine clearance and AA clearance (r=-0.42, p=0.009). There was a significant linear association between the quantity of albuminuria and ascorbic acid clearance (r=0.49, p=0.002). Thus, patients with diabetic nephropathy have reduced ascorbic acid levels due to increased ascorbic acid clearance. The decrease in antioxidant defense that arises from the low levels of vitamin C may contribute to the increased cardiovascular morbidity and mortality observed in this population.

Publication Types:

• Hypothesis

Publication Types:

• Review