Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis

Abstract

Objective: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.

Methods: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.

Results: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β₂-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β₂-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.

Conclusions: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Keywords: Astragalus; RAAS blockers; diabetic nephropathy; meta-analysis.

Figure 1.

Flow chart of article selection.

Figure 2.

Meta-analysis of total effective rate. OR, 3.63; 95% CI, 2.59, 5.09; p < 0.00001. CI: confidence interval; M-H: Mantel-Haenszel test; OR: odds ratio.

Figure 3.

Meta-analysis of urinary protein excretion rate. Mean difference, −24.76; 95% CI, −27.12, −22.39; p < 0.00001. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 4.

Meta-analysis of serum creatinine. Mean difference, −3.50; 95% CI, −4.91, -2.09; p < 0.00001. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 5.

Meta-analysis of blood urine nitrogen. Mean difference, −0.35; 95% CI, −0.50, − 0.19; p < 0.00001. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 6.

Meta-analysis of HbAlc. Mean difference, −0.17, 95% CI, −0.27, −0.07; p = 0.0006. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 7.

Meta-analysis of fasting plasma glucose. Mean difference, −0.28; 95% CI, −0.40, −0.17; p < 0.00001. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 8.

Meta-analysis of β₂-MG. Mean difference, −0.19; 95% CI, −0.27, −0.10; p < 0.0001. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 9.

Meta-analysis of 24 h urinary protein level. Mean difference, −48.24; 95% CI, −64.29, −32.18; p < 0.00001. CI: confidence interval; IV: inverse variance; SD: standard deviation.

Figure 10.

Funnel plots for UPER, BUN, HbAlc, FPG, and β₂-MG. (A) UPER; (B) BUN; (C) HbAlc; (D) FPG; (E) β₂-MG. β₂-MG: urinary microprotein; BUN: blood urine nitrogen; FPG: fasting plasma glucose; HbAlc: glycosylated hemoglobin; MD: mean difference; SEM: standard error of the mean; UPER: urinary protein excretion rate.