Effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycated end products, nitric oxide and endothelin-1 in patients with diabetic nephropathy

Diabetic nephropathy is the most common cause of kidney failure. High serum concentrations of advanced glycated end products, oxidative stress, and hypertension are three important risk factors for diabetic nephropathy. As individual administration of lipoic acid or pyridoxine is not effective in improving diabetic nephropathy, the present study was designed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycated end products, nitric oxide and endothelin-1 in patients with diabetic nephropathy. The study was a double-blind randomized clinical trial, in which 38 patients with diabetic nephropathy (23 females and 15 males) were randomly assigned to either a supplement-taking group or a placebo group. The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks, while the placebo group received placebos. At baseline and at the end of week 12, a urine sample and 8 ml blood were collected from each patient after a 12- to 14-hour fast and serum pentosidine, carboxymethyl lysine, malondialdehyde, endothelin-1, nitric oxide, glucose, urinary albumin, systolic and diastolic blood pressures were measured. The serum concentrations of pentosidine and carboxymethyl lysine decreased significantly in the supplement-taking group at the end of week 12 as compared to the baseline values (P<0.05). The combined supplement also brought about significant reductions in the serum malondialdehyde (25%), systolic blood pressure (2 mmHg) and urinary albumin concentration (74 mg/g creatinine); the reductions were significantly different from the placebo group values (P<0.05). On the other hand, the serum nitric oxide concentration increased significantly in the supplement-taking group as compared to the placebo group (P<0.05). No significant differences were observed between the two groups in the mean changes of serum endothelin-1, glucose or diastolic blood pressure. The results indicate that combined administration of lipoic acid and pyridoxine reduces significantly serum pentosidine, carboxymethyl lysine, malondialdehyde, systolic blood pressure and urinary albumin concentration, and increases serum nitric oxide. This treatment may, thus, have an effective role in retarding the progression of diabetic nephropathy.