Efficacy of Traditional Chinese Medicine Angiotensin-converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Their Combinations in the Treatment of IgA Nephropathy: a Systematic Review and Network Meta-analysis

Overview

Journal Front Pharmacol

Date 2024 Apr 5

PMID 38576485

Authors

Sijia Ma

Yuhua Jiang

Linlin Qian

Meng Wang

Shijie Xu

Guowei Wang

Affiliations

Soon will be listed here.

Abstract

Background: IgA nephropathy (IgAN), a condition posing a significant threat to public health, currently lacks a specific treatment protocol. Research has underscored the potential benefits of traditional Chinese medicine (TCM) for treating IgAN. Nevertheless, the effectiveness of various intervention strategies, such as combining TCM with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lacks a comprehensive systematic comparison. Therefore, this study aimed to conduct a network meta-analysis to assess the clinical efficacy of ACEIs, ARBs, TCM, and their combinations in treating IgAN to offer novel insights and approaches for the clinical management of IgAN.

Methods: A systematic review conducted until November 2023 included relevant literature from databases such as PubMed, Embase, Cochrane, Web of Science, Scopus, CNKI, and Wanfang. Two independent researchers screened and assessed the data for quality. Network and traditional meta-analyses were performed using Stata 18.0 and RevMan 5.3 software, respectively. Outcome measures included 24-h urinary protein quantification (24 hpro), estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), and adverse event incidence rates (ADRs). Forest plots, cumulative ranking probability curves (SUCRA), and funnel plots generated using Stata 18.0 facilitated a comprehensive analysis of intervention strategies' efficacy and safety.

Results: This study included 72 randomized controlled trials, seven interventions, and 7,030 patients. Comparative analysis revealed that ACEI + TCM, ARB + TCM combination therapy, and TCM monotherapy significantly reduced the levels of 24 hpro, eGFR, Scr, and BUN compared to other treatment modalities ( < 0.05). TCM monotherapy demonstrated the most favorable efficacy in reducing eGFR levels (SUCRAs: 78%), whereas the combination of ARB + TCM reduced Scr, 24 hpro, and BUN levels (SUCRAs: 85.7%, 95.2%, and 87.6%, respectively), suggesting that ARB + TCM may represent the optimal intervention strategy. No statistically significant differences were observed among the various treatment strategies in terms of ADR ( > 0.05).

Conclusion: The combination of ACEI or ARB with TCM demonstrated superior efficacy compared to ACEI/ARB monotherapy in the treatment of IgAN without any significant ADRs. Therefore, combination therapies can be used to enhance therapeutic outcomes based on individual patient circumstances, highlighting the use of TCM as a widely applicable approach in clinical practice.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023476674.

References

Inker L, Astor B, Fox C, Isakova T, Lash J, Peralta C . KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014; 63(5):713-35. DOI: 10.1053/j.ajkd.2014.01.416. View

Nakamura T, Inoue T, Sugaya T, Kawagoe Y, Suzuki T, Ueda Y . Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy. Am J Hypertens. 2007; 20(11):1195-201. DOI: 10.1016/j.amjhyper.2007.06.003. View

Guo D, Dong B, Wang Y . [Effect of treatment of non-nephrotic syndrome IgA nephropathy with Shenyanning]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010; 30(8):841-4. View

Chen X, Chen Y, Chen J . [Multicentered, randomized, controlled clinical trial on patients with IgA nephropathy of Qi-yin deficiency syndrome type]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007; 27(2):101-5. View

Chen X, Chen Y, Zhou Z . [Prospective, multi-centered, randomized and controlled trial on effect of Shenle Capsule in treating patients with IgA nephropathy of Fei-Pi qi-deficiency syndrome]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007; 26(12):1061-5. View

Yao T, Wu Z, Wang Z, Chen L, Liu B, Lu M . Association between angiotensin-converting enzyme inhibitor-induced cough and the risk of lung cancer: a Mendelian randomization study. Front Pharmacol. 2023; 14:1267924. PMC: 10550256. DOI: 10.3389/fphar.2023.1267924. View

Rajasekaran A, Julian B, Rizk D . IgA Nephropathy: An Interesting Autoimmune Kidney Disease. Am J Med Sci. 2020; 361(2):176-194. PMC: 8577278. DOI: 10.1016/j.amjms.2020.10.003. View

Shen P, He L, Yang X, Cao H . Renal protection of losartan 50 mg in normotensive Chinese patients with nondiabetic chronic kidney disease. J Investig Med. 2012; 60(7):1041-7. DOI: 10.2310/JIM.0b013e31826741d2. View

Karoui K, Fervenza F, De Vriese A . Treatment of IgA Nephropathy: A Rapidly Evolving Field. J Am Soc Nephrol. 2023; 35(1):103-116. PMC: 10786616. DOI: 10.1681/ASN.0000000000000242. View

10.

Shima Y, Nakanishi K, Sako M, Saito-Oba M, Hamasaki Y, Hataya H . Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatr Nephrol. 2018; 34(5):837-846. DOI: 10.1007/s00467-018-4099-8. View

11.

Lv J, Zhang H, Wong M, Jardine M, Hladunewich M, Jha V . Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017; 318(5):432-442. PMC: 5817603. DOI: 10.1001/jama.2017.9362. View

12.

Rovin B, Adler S, Barratt J, Bridoux F, Burdge K, Chan T . Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021; 100(4):753-779. DOI: 10.1016/j.kint.2021.05.015. View

13.

Samarghandian S, Azimi-Nezhad M, Farkhondeh T, Samini F . Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomed Pharmacother. 2017; 87:223-229. DOI: 10.1016/j.biopha.2016.12.105. View

14.

Zhang L, Li P, Xing C, Zhao J, He Y, Wang J . Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial. Am J Kidney Dis. 2014; 64(1):57-65. DOI: 10.1053/j.ajkd.2014.01.431. View

15.

Guan X, Wu Y, Zhao W . [Clinical observation on treatment of IgA nephropathy with Huobahuagen Tablets and irbesartan]. Zhong Xi Yi Jie He Xue Bao. 2005; 3(5):366-9. DOI: 10.3736/jcim20050509. View

16.

Eftekhari A, Hasanzadeh A, Khalilov R, Hosainzadegan H, Ahmadian E, Eghbal M . Hepatoprotective role of berberine against paraquat-induced liver toxicity in rat. Environ Sci Pollut Res Int. 2019; 27(5):4969-4975. DOI: 10.1007/s11356-019-07232-1. View

17.

Wang X, Lang R, Liang Y, Zeng Q, Chen N, Yu R . Traditional Chinese Medicine in Treating IgA Nephropathy: From Basic Science to Clinical Research. J Transl Int Med. 2021; 9(3):161-167. PMC: 8629415. DOI: 10.2478/jtim-2021-0021. View

18.

Renke M, Tylicki L, Rutkowski P, Rutkowski B . Low-dose angiotensin II receptor antagonists and angiotensin II-converting enzyme inhibitors alone or in combination for treatment of primary glomerulonephritis. Scand J Urol Nephrol. 2005; 38(5):427-33. DOI: 10.1080/00365590410015687. View

19.

Schimpf J, Kronbichler A, Windpessl M, Zitt E, Eller K, Saemann M . [Diagnosis and Treatment of IgA Nephropathy-2023]. Wien Klin Wochenschr. 2023; 135(Suppl 5):621-627. PMC: 10511560. DOI: 10.1007/s00508-023-02257-6. View

20.

Whitlock R, Leon S, Manacsa H, Askin N, Rigatto C, Fatoba S . The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant. 2023; 38(11):2503-2516. PMC: 10615629. DOI: 10.1093/ndt/gfad101. View