Effect of Oral Carnosine Supplementation on Urinary TGF-β in Diabetic Nephropathy: a Randomized Controlled Trial

Abstract Background: Activation of the transforming growth factor beta (TGF-b) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is an amino acid that can inhibit TGF-b synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-b levels among patients with diabetic nephropathy. Methods: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-b level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-b.Results: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-b and renal function measurements. Urinary TGF-b significantly decreased with carnosine supplement (-17.8% of the baseline values), whereas it tended to increase with placebo (+16.9% of the baseline values) (between-group difference P <0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects.Conclusions: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-b level that serves as a marker of renal injury in diabetic nephropathy. Trial registration Thai Clinical Trials, TCTR20200724002. Retrospectively Registered 24 July 2020.