Efficacy and Safety of Renin-Angiotensin Aldosterone System Inhibitor in Patients with IgA Nephropathy: A Meta-Analysis of Randomized Controlled Trials
Background: Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) as the commonly used renin-angiotensin aldosterone system inhibitor are widely used in patients with IgA nephropathy (IgAN), but the effect is controversy. In this study, we used a meta-analysis to evaluate the efficacy and safety of ACEI and/or ARB for the patients with IgAN.
Methods: Two investigators independently searched the PubMed, EMBASE, the Cochrane Library, EBSCO, and Wiley databases without language restrictions. We collected the clinical randomized controlled trials (RCTs) on “ACEI and/or ARB for the patients with IgAN” published before December 31, 2018, and performed data extraction and quality analysis on the included studies, and analyzed data using RevMan 5.2 software.
Results: A total of 10 RCTs (635 patients) were included in our analysis. Alone use of ACEI (MD=-0.75, 95%CI: -1.28-0.21, P=0.006) or ARB (MD=-0.56, 95%CI: -0.82-0.30, P< 0.001) or a combination of ACEI and ARB (MD=-0.63, 95%CI: -0.87-0.38, P<0.001) significantly reduced the levels of proteinuria in patients with IgAN. However, whether using ACEI or ARB alone or in combination with ACEI and ARB, there was no significant effect on serum creatinine, 24-creatinine clearance and glomerular filtration rate in patients with IgAN.
Conclusion: The use of ACEI and ARB significantly reduces the levels of proteinuria in patients with IgAN, but more large-sample RCTs with long-term follow-up are needed for confirming our results and guiding clinical treatment.
2. Selvaskandan H, Cheung CK, Muto M, Bar-ratt J (2019). New strategies and perspec-tives on managing IgA nephropathy. Clin Exp Nephrol, 23(5):577-88.
3. Andeen NK, Jefferson JA, Akilesh S, et al (2018). IgA-dominant glomerulonephritis with a membranoproliferative pattern of injury. Hum Pathol, 81:272-80.
4. Zhang JJ, Yu GZ, Zheng ZH, et al (2017). Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA nephropathy. PLoS One, 12(4):e0175828.
5. Oshima Y, Moriyama T, Itabashi M, et al (2015). Characteristics of IgA nephropa-thy in advanced-age patients. Int Urol Nephrol, 47(1):137-45.
6. Imai N, Shirai S, Yasuda T, et al (2016). Long-term prognosis of IgA nephropa-thy presenting with minimal or no pro-teinuria: A single center experience. Indian J Nephrol, 26(2):107-12.
7. Park S, Baek CH, Park SK, et al (2019). Clin-ical Significance of Crescent Formation in IgA Nephropathy - a Multicenter Valida-tion Study. Kidney Blood Press Res, 44(1):22-32.
8. Liu D, You J, Liu Y, et al (2019). Serum im-munoglobulin G provides early risk pre-diction in immunoglobulin A nephropa-thy. Int Immunopharmacol, 66:13-8.
9. Woo KT, Lau YK, Wong KS, Chiang GS (2000). ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis. Kidney Int, 58(6):2485-91.
10. Nakamura T, Ushiyama C, Suzuki S, et al (2000). Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on uri-nary podocytes in patients with IgA nephropathy. Am J Nephrol, 20(5):373-9.
11. Shi X, Chen X, Liu S, et al (2002). The ef-fects of angiotensin-converting enzyme inhibitor on IgA nephropathy and the in-fluencing factors. Zhonghua Nei Ke Za Zhi, 41(6):399-403.(Article in Chinese)
12. Praga M, Gutiérrez E, González E, et al (2003). Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol, 14(6):1578-83.
13. Kim MJ, Song JH, Suh JH, et al (2003). Ad-ditive antiproteinuric effect of combina-tion therapy with ACE inhibitor and an-giotensin II receptor antagonist: differen-tial short-term response between IgA nephropathy and diabetic nephropathy. Yonsei Med J, 44(3):463-72.
14. Li PK, Leung CB, Chow KM, et al (2006). Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis, 47(5):751-60.
15. Coppo R, Peruzzi L, Amore A, et al (2007). IgACE: a placebo-controlled, random-ized trial of angiotensin-converting en-zyme inhibitors in children and young people with IgA nephropathy and mod-erate proteinuria. J Am Soc Nephrol, 18(6):1880-8.
16. Shimizu A, Takei T, Uchida K, et al (2008). Low-dose losartan therapy reduces pro-teinuria in normotensive patients with immunoglobulin A nephropathy. Hyper-tens Res, 31(9):1711-7.
17. Li PK, Kwan BC, Chow KM, et al (2013). Treatment of early immunoglobulin A nephropathy by angiotensin-converting enzyme inhibitor. Am J Med, 126(2):162-8.
18. Kohagura K, Arima H, Miyasato H, et al (2018). Add-On Effect of Angiotensin Receptor Blockade (Candesartan) on Clinical Remission in Active IgA Nephropathy Patients Treated with Ster-oid Pulse Therapy and Tonsillectomy: a Randomized, Parallel-Group Comparison Trial. Kidney Blood Press Res, 43(3):780-92.
19. Coppo R (2018). Treatment of IgA nephropathy: Recent advances and pro-spects. Nephrol Ther, 14 Suppl 1:S13-S21.
20. Shima Y, Nakanishi K, Sako M, et al (2019). Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatr Nephrol, 34(5):837-46.
21. Nakamura T, Inoue T, Sugaya T, et al (2007). Beneficial effects of olmesartan and te-mocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy. Am J Hypertens, 20(11):1195-201.
22. Tam FWK, Pusey CD (2018). TESTING corticosteroidsin IgA nephropathy: a continuing challenge. Clin J Am Soc Neph-rol, 13(1):158-160.
23. Lv J, Zhang H, Wong MG, et al (2017). Ef-fect of oral methylprednisolone on clini-cal outcomes in patients with IgA nephropathy: the TESTING Random-ized Clinical Trial. JAMA, 318 (5):432–42.
24. Qian G, Zhang X, Xu W, et al (2019). Effi-cacy and safety of glucocorticoids for pa-tients with IgA nephropathy: a meta-analysis. Int Urol Nephrol, 51(5):859-68.
25. Glassock RJ (2019). Mortality Risk in IgA Nephropathy. J Am Soc Nephrol, 30(5):720-2.
26. Horita Y, Taura K, Taguchi T, et al (2006). Aldosterone breakthrough during therapy with angiotensin-converting enzyme in-hibitors and angiotensin II receptor blockers in proteinuric patients with im-munoglobulin A nephropathy. Nephrology (Carlton), 11(5):462-6.
27. Pozzi C, Del Vecchio L, Casartelli D, et al (2006). ACE inhibitors and angiotensin II receptor blockers in IgA nephropathy with mild proteinuria: the ACEARB study. J Nephrol, 19(4):508-14.
28. Ji Y, Yang K, Xiao B, et al (2019). Efficacy and safety of angiotensin-converting en-zyme inhibitors/angiotensin receptor blocker therapy for IgA nephropathy: A meta-analysis of randomized controlled trials. J Cell Biochem, 120(3):3689-95.
29. Cheng J, Zhang X, Tian J, et al (2012). Combination therapy an ACE inhibitor and an angiotensin receptor blocker for IgA nephropathy: a meta-analysis. Int J Clin Pract, 66(10):917-23.