Losartan Monotherapy vs Combination Regimens in IgA Nephropathy: A Systematic Review and Network Meta-analysis
Downloads
DOI:
https://doi.org/10.71079/ASIDE.IM.012726340Abstract
Background: IgA nephropathy (IgAN) is a disorder in which Immunoglobulin A (IgA) antibodies build up, causing kidney damage. Losartan, an Angiotensin Receptor Blocker (ARB), has shown promise in patients with IgAN. However, a comparison of losartan with other IgAN therapies is missing. This study investigates the efficacy of losartan compared to different regimens.
Methods: A systematic search of four electronic databases was conducted till January 2025. The study was registered in PROSPERO (CRD42025634499). Risk of bias assessment was performed using the ROB-2 tool.
Results: The study included five RCTs in the quantitative analysis. Although losartan + temocapril ranked first in systolic blood pressure (SBP) and diastolic blood pressure (DBP) reductions at 12 months [surface under the cumulative ranking curve (SUCRA) = 97% and 86%, respectively], pairwise comparisons versus losartan were not statistically significant, so clinical superiority is uncertain. Additionally, compared to temocapril, losartan + temocapril and losartan demonstrated statistically significant reductions in SBP at 12 months. Regarding proteinuria reduction, none of the interventions demonstrated a statistically significant difference compared to losartan at 3 and 6 months. However, mizoribine and mizoribine + losartan showed a statistically significantly greater reduction in proteinuria than losartan at 12 months.
Conclusions: Among patients with IgAN from East Asian cohorts, mizoribine and mizoribine + losartan best reduced proteinuria at 12 months. Regarding BP, losartan + temocapril best reduced SBP and DBP at 12 months. However, clinical superiority is uncertain, and estimates were imprecise due to limited power.
Keywords:
Losartan, IgA Nephropathy, Urinary Protein Excretion, Network meta-analysisReferences
1. Julian BA, Waldo FB, Rifai A, Mestecky J. IgA nephropathy, the most common glomerulonephritis worldwide. A neglected disease in the United States? Am J Med. 1988: 129 [PMID: 3337116, https://doi.org/10.1016/0002-9343(88)90019-8] DOI: https://doi.org/10.1016/0002-9343(88)90019-8
2. Willey CJ, Coppo R, Schaefer F, Mizerska-Wasiak M, Mathur M, Schultz MJ. The incidence and prevalence of IgA nephropathy in Europe. Nephrol Dial Transplant. 2023: 2340 [PMID: 37156519, https://doi.org/10.1093/ndt/gfad082] DOI: https://doi.org/10.1093/ndt/gfad082
3. Kiryluk K, Freedberg DE, Radhakrishnan J, Segall L, Jacobson JS, Mathur M, Mohan S, Neugut AI. Global Incidence of IgA Nephropathy by Race and Ethnicity: A Systematic Review. Kidney360. 2023: 1112 [PMID: 37227924, https://doi.org/10.34067/KID.0000000000000165] DOI: https://doi.org/10.34067/KID.0000000000000165
4. Shen PC, He LQ, Tang Y, Wang Q, Wang W, Li J. Clinicopathological characteristics and prognostic factors of asymptomatic IgA nephropathy. J Investig Med. 2010: 560 [PMID: 20215916, https://doi.org/10.231/JIM.0b013e3181d20aa1] DOI: https://doi.org/10.2310/JIM.0b013e3181d20aa1
5. Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011: 1795 [PMID: 21949093, https://doi.org/10.1681/ASN.2011050464] DOI: https://doi.org/10.1681/ASN.2011050464
6. Ohashi N, Urushihara M, Kobori H. Activated intrarenal reactive oxygen species and renin angiotensin system in IgA nephropathy. Minerva Urol Nefrol. 2009: 55 [PMID: 19417726, DOI: https://doi.org/10.1111/j.1440-1681.2009.05172.x
7. Fabiano RC, Pinheiro SV, Simoes ESAC. Immunoglobulin A nephropathy: a pathophysiology view. Inflamm Res. 2016: 757 [PMID: 27351940, https://doi.org/10.1007/s00011-016-0962-x] DOI: https://doi.org/10.1007/s00011-016-0962-x
8. D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. 2000: 227 [PMID: 10922300, https://doi.org/10.1053/ajkd.2000.8966] DOI: https://doi.org/10.1053/ajkd.2000.8966
9. Lv J, Xu D, Perkovic V, Ma X, Johnson DW, Woodward M, Levin A, Zhang H, Wang H, Group TS. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012: 1108 [PMID: 22539830, https://doi.org/10.1681/ASN.2011111112] DOI: https://doi.org/10.1681/ASN.2011111112
10. Horita Y, Tadokoro M, Taura K, Suyama N, Taguchi T, Miyazaki M, Kohno S. Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy. Hypertens Res. 2004: 963 [PMID: 15894837, https://doi.org/10.1291/hypres.27.963] DOI: https://doi.org/10.1291/hypres.27.963
11. Peresuodei TS, Gill A, Orji C, Reghefaoui M, Saavedra Palacios MS, Nath TS. A Comparative Study of the Safety and Efficacy Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Management of Hypertension: A Systematic Review. Cureus. 2024: e54311 [PMID: 38496070, https://doi.org/10.7759/cureus.54311] DOI: https://doi.org/10.7759/cureus.54311
12. Rout P, Afzal M. IgA Nephropathy (Berger Disease). StatPearls. Treasure Island (FL): StatPearls Publishing
Copyright © 2025, StatPearls Publishing LLC.; 2025.
13. Kobori H, Mori H, Masaki T, Nishiyama A. Angiotensin II blockade and renal protection. Curr Pharm Des. 2013: 3033 [PMID: 23176216, https://doi.org/10.2174/1381612811319170009] DOI: https://doi.org/10.2174/1381612811319170009
14. Shimizu A, Takei T, Uchida K, Tsuchiya K, Nitta K. Low-dose losartan therapy reduces proteinuria in normotensive patients with immunoglobulin A nephropathy. Hypertens Res. 2008: 1711 [PMID: 18971549, https://doi.org/10.1291/hypres.31.1711] DOI: https://doi.org/10.1291/hypres.31.1711
15. Park HC, Xu ZG, Choi S, Goo YS, Kang SW, Choi KH, Ha SK, Lee HY, Han DS. Effect of losartan and amlodipine on proteinuria and transforming growth factor-beta1 in patients with IgA nephropathy. Nephrol Dial Transplant. 2003: 1115 [PMID: 12748343, https://doi.org/10.1093/ndt/gfg090] DOI: https://doi.org/10.1093/ndt/gfg090
16. Horita Y, Tadokoro M, Taura K, Ashida R, Hiu M, Taguchi T, Furusu A, Kohno S. Prednisolone co-administered with losartan confers renoprotection in patients with IgA nephropathy. Ren Fail. 2007: 441 [PMID: 17497466, https://doi.org/10.1080/08860220701260511] DOI: https://doi.org/10.1080/08860220701260511
17. Xie Y, Huang S, Wang L, Miao L, Zhang A, Li Y, Wu X, Wang L, Liu S, Lie C, Chen P, Chen X. Efficacy and safety of mizoribine combined with losartan in the treatment of IgA nephropathy: a multicenter, randomized, controlled study. Am J Med Sci. 2011: 367 [PMID: 21293249, https://doi.org/10.1097/MAJ.0b013e318207e02d] DOI: https://doi.org/10.1097/MAJ.0b013e318207e02d
18. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Moher D. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol. 2021: 103 [PMID: 33577987, https://doi.org/10.1016/j.jclinepi.2021.02.003] DOI: https://doi.org/10.1016/j.jclinepi.2021.02.003
19. Blood Pressure Lowering Treatment Trialists C. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021: 1625 [PMID: 33933205, https://doi.org/10.1016/S0140-6736(21)00590-0] DOI: https://doi.org/10.1016/S0140-6736(21)00590-0
20. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016: 957 [PMID: 26724178, https://doi.org/10.1016/S0140-6736(15)01225-8] DOI: https://doi.org/10.1016/S0140-6736(15)01225-8
21. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernan MA, Hopewell S, Hrobjartsson A, Junqueira DR, Juni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019: l4898 [PMID: 31462531, https://doi.org/10.1136/bmj.l4898] DOI: https://doi.org/10.1136/bmj.l4898
22. R. The R Project for Statistical Computing.
23. Russo D, Minutolo R, Pisani A, Esposito R, Signoriello G, Andreucci M, Balletta MM. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis. 2001: 18 [PMID: 11431176, https://doi.org/10.1053/ajkd.2001.25176] DOI: https://doi.org/10.1053/ajkd.2001.25176
24. Horita Y, Taura K, Taguchi T, Furusu A, Kohno S. Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy. Nephrology (Carlton). 2006: 462 [PMID: 17014562, https://doi.org/10.1111/j.1440-1797.2006.00665.x] DOI: https://doi.org/10.1111/j.1440-1797.2006.00665.x
25. Shima Y, Nakanishi K, Sako M, Saito-Oba M, Hamasaki Y, Hataya H, Honda M, Kamei K, Ishikura K, Ito S, Kaito H, Tanaka R, Nozu K, Nakamura H, Ohashi Y, Iijima K, Yoshikawa N, Japanese Study Group of Kidney Disease in C. Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatr Nephrol. 2019: 837 [PMID: 30284023, https://doi.org/10.1007/s00467-018-4099-8] DOI: https://doi.org/10.1007/s00467-018-4099-8
26. Yokota S. Mizoribine: mode of action and effects in clinical use. Pediatr Int. 2002: 196 [PMID: 11896886, https://doi.org/10.1046/j.1328-8067.2002.01536.x] DOI: https://doi.org/10.1046/j.1328-8067.2002.01536.x
27. Hirohata S, Nakanishi K, Yanagida T. Inhibition of cyclin A gene expression in human B cells by an immunosuppressant mizoribine. Clin Exp Immunol. 2000: 448 [PMID: 10844522, https://doi.org/10.1046/j.1365-2249.2000.01242.x] DOI: https://doi.org/10.1046/j.1365-2249.2000.01242.x
28. Seo KW, Lee HK, Choi SJ, So BJ, Kim SK, Chung SY. Mizoribine-mediated apoptotic signaling pathway in human T-Cell line. Transplant Proc. 2005: 155 [PMID: 15808579, https://doi.org/10.1016/j.transproceed.2005.01.020] DOI: https://doi.org/10.1016/j.transproceed.2005.01.020
29. Kaneko K, Nagaoka R, Ohtomo Y, Shimizu T, Yamashiro Y. Effect of mizoribine on IL-6 release by peripheral blood mononuclear cells. Nephron. 2002: 506 [PMID: 12119487, https://doi.org/10.1159/000064297] DOI: https://doi.org/10.1159/000064297
30. Yoshikawa N, Nakanishi K, Ishikura K, Hataya H, Iijima K, Honda M, Japanese Pediatric Ig ANTSG. Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study. Pediatr Nephrol. 2008: 757 [PMID: 18224343, https://doi.org/10.1007/s00467-007-0731-8] DOI: https://doi.org/10.1007/s00467-007-0731-8
31. Praga M, Andrade CF, Luno J, Arias M, Poveda R, Mora J, Prat MV, Rivera F, Galceran JM, Ara JM, Aguirre R, Bernis C, Marin R, Campistol JM. Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial. Nephrol Dial Transplant. 2003: 1806 [PMID: 12937228, https://doi.org/10.1093/ndt/gfg284] DOI: https://doi.org/10.1093/ndt/gfg284
32. Hartmann A, Lund K, Holdaas H, Fauchald P, Reisaeter A, Berg KJ. Contrasting short-term effects of nifedipine on glomerular and tubular functions in glomerulonephritic patients. J Am Soc Nephrol. 1994: 1385 [PMID: 7534496, https://doi.org/10.1681/ASN.V561385] DOI: https://doi.org/10.1681/ASN.V561385
33. Holdaas H, Hartmann A, Lien MG, Nilsen L, Jervell J, Fauchald P, Endresen L, Djoseland O, Berg KJ. Contrasting effects of lisinopril and nifedipine on albuminuria and tubular transport functions in insulin dependent diabetics with nephropathy. J Intern Med. 1991: 163 [PMID: 1847721, https://doi.org/10.1111/j.1365-2796.1991.tb00325.x] DOI: https://doi.org/10.1111/j.1365-2796.1991.tb00325.x
34. Krusell LR, Christensen CK, Lederballe Pedersen O. Acute natriuretic effect of nifedipine in hypertensive patients and normotensive controls--a proximal tubular effect? Eur J Clin Pharmacol. 1987: 121 [PMID: 3556192, https://doi.org/10.1007/BF00542183] DOI: https://doi.org/10.1007/BF00542183
35. Hoelscher D, Bakris G. Antihypertensive therapy and progression of diabetic renal disease. J Cardiovasc Pharmacol. 1994: S34 [PMID: 7519695, https://doi.org/10.1097/00005344-199423001-00008] DOI: https://doi.org/10.1097/00005344-199423001-00008
36. Huo Z, Ye H, Ye P, Xiao G, Zhang Z, Kong Y. Comparative efficacy of different renin angiotensin system blockade therapies in patients with IgA nephropathy: a Bayesian network meta-analysis of 17 RCTs. PeerJ. 2021: e11661 [PMID: 34268008, https://doi.org/10.7717/peerj.11661] DOI: https://doi.org/10.7717/peerj.11661
37. Cheng J, Zhang X, Tian J, Li Q, Chen J. Combination therapy an ACE inhibitor and an angiotensin receptor blocker for IgA nephropathy: a meta-analysis. Int J Clin Pract. 2012: 917 [PMID: 22994326, https://doi.org/10.1111/j.1742-1241.2012.02970.x] DOI: https://doi.org/10.1111/j.1742-1241.2012.02970.x
38. Remuzzi A, Perico N, Sangalli F, Vendramin G, Moriggi M, Ruggenenti P, Remuzzi G. ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity in IgA nephropathy. Am J Physiol. 1999: F457 [PMID: 10070170, https://doi.org/10.1152/ajprenal.1999.276.3.F457] DOI: https://doi.org/10.1152/ajprenal.1999.276.3.F457
39. Woo KT, Lau YK, Wong KS, Chiang GS. ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis. Kidney Int. 2000: 2485 [PMID: 11115082, https://doi.org/10.1046/j.1523-1755.2000.00432.x] DOI: https://doi.org/10.1046/j.1523-1755.2000.00432.x
Data Availability Statement
All data generated or analyzed during this study are included in this published manuscript [and its supplementary file]. The code details will be provided by the authors on request.
License
Copyright (c) 2026 Mohamed E. Haseeb, Hazem E. Mohammed, Anas Hussein Heiba, George Hanen, Nada Ali Omar Abd Elaziz, Mohamed Nasser
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright and Licensing
All articles published in ASIDE Internal Medicine are open access and freely available online immediately upon publication, without embargo.
This journal applies the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). Under this license, anyone may copy, redistribute, remix, transform, and build upon the material for any purpose, even commercially, provided that proper credit is given to the original author(s), a link to the license is provided, and any changes made are indicated.
-
License link: https://creativecommons.org/licenses/by/4.0/
-
Machine-readable license metadata is embedded in each article and its DOI record.
Copyright Holder
Copyright in all articles remains with the author(s). By submitting a manuscript, authors agree to grant the publisher (American Society for Inclusion, Diversity, and Equity in Healthcare – ASIDE) a non-exclusive license to publish and distribute the work under the terms of the CC BY 4.0 license.
Third-party Material
Any material (e.g., images, figures, or tables) not covered by CC BY 4.0 will be clearly indicated in the article. Users must obtain permission directly from the copyright holder for reuse of such third-party material.
Author Rights and Self-Archiving
Authors are permitted to deposit all versions of their work (preprint, author’s accepted manuscript, and version of record) in institutional or subject repositories of their choice immediately upon publication, without embargo, provided that the DOI and license information are included.
Downloads
Published
Issue
Section
Categories
How to Cite
Article history
- Received
- 25 Oct 2025
- Received in revised form
- 9 Jan 2026
- Accepted
- 23 Jan 2026
- Published
- 27 Jan 2026
