13 months vs 19.63 months, P = 0.019). The rate of 24-h urinary protein decrease after valsartan treatment in the present study is consistent Epacadostat mw with previous studies. For example, the HKVIN study of patients on ARBs showed that the 24-h urinary protein was reduced from 1.80 ± 1.24 g at baseline to 1.26 ± 1.21 g at week 52, and to 1.23 ± 1.25 g at week 104 (P < 0.001).[15] Previous study in the rat indicated that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression

in GN.[16]Another study also demonstrated that treatment with an anti-oxidant, alpha-Tocopherol, alone reduced urinary protein in IgA nephropathy in the rat.[17]Consistent with these animals’ results, our data also indicated that during the first 2 years of treatment, probucol Z-VAD-FMK in vivo (an antioxidant and anti-hyperlipidemic agent) in combination with valsartan rapidly reduced urinary protein, a response known to decrease the risk for ESRD in high risk IgA nephropathy patients.[12] This more rapid reduction in urinary protein in the combined therapy group compared to valsartan treatment alone might be due to the potent anti-oxidative effects of probucol.[16] In addition, patients receiving probucol had a decline in plasma cholesterol in the early phases of treatment, but an increase in the later

phases of treatment. These changes in plasma cholesterol paralleled the changes in urinary protein excretion. Previous clinical trials also demonstrated that lowering cholesterol with statin regimens were able

to decrease proteinuria and to improve renal function.[18, 19] Therefore, we cannot rule out the probability of urinary protein reduction is due to the effect of probucol in lowering cholesterol. During the first 2 years of follow-up in our patients, urinary protein tended to decrease. Previous studies reported that urinary protein decreased at 3 months to 2 years after initiation of therapy,[20-22] which was consistent with our findings. However, we noted that urinary protein had increased Thiamine-diphosphate kinase at the 2- and 3-year follow-ups, especially in the valsartan (control) group at 2 years. At the end of the study, the 24-h urinary protein levels were comparable to the baseline levels in both groups. This suggests that 750 mg probucol combined with 160 mg valsartan may decrease proteinuria, but the long-term effect remained less convincing. This might be a result of an increase in oxidative stress due to the development of compromised endogenous anti-oxidative responses over the course of 3 years. Disruption of the immune response has a role in the pathogenesis of IgA nephropathy.[23, 24] oxidative stress was only as a minor reason. So the absence of steroids and/or immunosuppressants fails to forestall disease progression.