Probucol combined with valsartan in immunoglobulin A nephropathy: A multi-centre, open labelled, randomized controlled study

Aim Angiotensin receptor antagonists (ARBs) and anti‐oxidants reduce urinary protein excretion and delay progression of immunoglobulin A (IgA) nephropathy. We investigated the efficacy and safety of probucol (an anti‐oxidant) combined with valsartan (an ARB) on the progression of IgA nephropathy. Methods Patients with IgA nephropathy (n = 69) were recruited from five centres and randomly assigned to a treatment group (750 mg/day probucol plus 160 mg/day valsartan) or a control group (160 mg/day valsartan) and were followed for 3 years. Results At baseline, the two groups in any measured clinical information were comparable. The primary endpoint (doubling serum creatinine) showed no significant difference between the two groups during 3‐year follow‐up. The secondary endpoint (50% reduction in 24‐h urinary protein) occurred in 23 patients in the treatment group and 20 patients in the control group. The time to the secondary end‐point was shorter in the treatment group than the control group (8.13 months vs 19.63 months, P = 0.019). However, at the 3‐year follow‐up, the 24‐h urinary protein levels were not significantly different from the baseline levels (P = 0.99 and P = 0.66, respectively). At the 1‐year follow‐up, plasma cholesterol in the treatment group was markedly lower than in the control group (4.12 ± 1.28 vs 5.03 ± 1.01, P = 0.02). Conclusion Kidney function remained stable and there was no significant difference in two group patients. Probucol combined with valsartan led to a more rapid decrease of 24‐h urinary protein excretion than valsartan alone. However, the long‐term effect needs further investigation. Summary at a Glance The anti‐proteinuric effects of lipid lowering agents, including potential effects that are independent of cholesterol, are unclear. Probucol was shown to be anti‐proteinuric in experimental nephritis some years ago. Wei et al. have shown, in a controlled trial, potential adjunctive effects of probucol on early proteinuria in IgA nephropathy when combined with valsartan.