Yi-Shen-Hua-Shi regulates intestinal microbiota dysbiosis and protects against proteinuria in patients with chronic kidney disease: a randomized controlled study

Abstract

Context

Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.

Objective

This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.

Materials and methods

120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.

Results

Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.

Discussion and conclusion

The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.

Trial registration

ChiCTR2300076136, retrospectively registered.

Keywords:

• Yi-Shen-Hua-Shi
• proteinuria
• chronic kidney disease
• gut flora
• microbiota dysbiosis

Authors’ contribution

A.H.Z. contributed to the study concept and design; J.L.Z, X.T.D, W.L, Y.P.L, L.P.J, Z.H.L, W.J.F contributed to data collection; J.L.Z, X.T.D contributed to the statistical analysis; J.L.Z, X.T.D, A.H.Z contributed to the original draft. J.L.Z and X.T.D contributed equally. All authors approved the final version of the manuscript.

Ethical approval

The study was conducted following the guidelines stated in the Declaration of Helsinki. All patients gave their written informed consent to the protocol, which was approved by the Medical Ethics Committee of Xuanwu Hospital, Capital Medical University guidelines. This project was approved by the Xuanwu Hospital Medical Ethic Committee [No.2020(025)].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data described in the manuscript will be made available upon reasonable request.

Additional information

Funding

This study was supported by Clinical and Experimental Research for the YSHS Granule.