OBJECTIVES: Studies showed dual blockade of renin-angiotensin-aldosterone system  with ACEI and ARB had produced little gain with significant side effects in proteinuric patients. Here we evaluated the real-world effectiveness of long-term antiproteinuric effects of a novel dual blockade with the direct renin inhibitor aliskiren addition on chronic ACEI or ARB treatment in diabetic patients with persistent albuminuria. METHODS: We retrospectively collected data from the electronic database of Baywest Endocrinology Associates. Aliskiren150- 300mg daily was added on chronic ACEI/ARB treatment (mean known duration 6 years). The Cockroft-Gault formula was used to estimate the glomerular filtration rate (eGFR). The Wilcoxon Signed Ranks test and Kendall’s tau-b correlation analysis were used to calculate statistical significance. p<0.05 was considered significant. RESULTS: Twenty-four (mean age 64 years) patients were selected, with a mean observation time 15 months before and 20 months after aliskiren addition. There was a significant rise in urinary albumin-to-creatinine ratio (Ualb/Cr) [unit: mg/g, 146.3 (16.1-1978.7) vs. 51.0 (34-1170.3)] and SBP (unit: mmHg, 158 ± 19 vs. 142± 21) in these patients at baseline (i.e., when Aliskiren was added) when compared with that of 15 months before (p<0.05). And there was a significant decline in albuminuria and SBP 20 months after aliskiren addition: reduced median Ualb/Cr was 73.3%, reduced mean SBP was 24 mmHg (p=0.001). However, reduction in Ualb/Cr was not related to reduction in SBP (p>0.05).  No changes were found in the DBP, HbA1c, serum creatinine and eGFR.  A small increment of serum potassium levels was detected after aliskiren addition( unit: mmol/L, 4.5±0.6 vs 4.4  ± 0.4 mmol/L at baseline, p<0.05 ). During the study, no adverse events, including symptoms of hyperkalemia and hypotension, were documented.  CONCLUSIONS: Aliskiren addition to ACEI/ARB may have extra antiproteinuric effects that might be independent on BP reduction and held without rebound as long as 1.5 year follow-up.