The effectiveness and safety of corticosteroid therapy for IgA nephropathy with crescents: a prospective, randomized, controlled study

Mengjun Liang, Liping Xiong, Aihua Li, Jiafan Zhou, Yajuan Huang, Miaofang Huang, Xing Zhang, Hongrui Shi, Ning Su, Yi Wei, Zongpei Jiang, Mengjun Liang, Liping Xiong, Aihua Li, Jiafan Zhou, Yajuan Huang, Miaofang Huang, Xing Zhang, Hongrui Shi, Ning Su, Yi Wei, Zongpei Jiang

Abstract

Background: Pozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents.

Methods: In this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels).

Results: There was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups.

Conclusions: Both the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness.

Trial registration: ClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.

Keywords: Corticosteroid therapy; Crescents; IgA nephropathy.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Enrollment flow diagram
Fig. 2
Fig. 2
The changes of urine protein (A), serum creatinine (B), and eGFR (C) over time
Fig. 3
Fig. 3
The Kaplan-Meier survival functions of 1–2-3 and 1–3-5 groups to total remission (CR + PR) (A), and CR only (B)

References

    1. Li LS, Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int. 2004;66:920–923. doi: 10.1111/j.1523-1755.2004.00837.x.
    1. Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L. Predicting the risk for dialysis or death in IgA nephropathy. J Am Soc Nephrol. 2011;22:752–761. doi: 10.1681/ASN.2010040355.
    1. Coppo R, D’Amico G. Factors predicting progression of IgA nephropathies. Journal of Nephrology. 2005;18:503–512.
    1. Tan M, Li W, Zou G, Zhang C, Fang J. Clinicopathological features and outcomes of IgA nephropathy with hematuria and/or minimal proteinuria. Kidney Blood Press Res. 2015;40:200–206. doi: 10.1159/000368495.
    1. Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, et al. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91:1014–1021. doi: 10.1016/j.kint.2017.02.003.
    1. Markowitz G. Glomerular disease: updated Oxford classification of IgA nephropathy: a new MEST-C score. Nat Rev Nephrol. 2017;13:385–386. doi: 10.1038/nrneph.2017.67.
    1. Park S, Baek CH, Park SK, Kang HG, Hyun HS, Park E, et al. Clinical significance of crescent formation in IgA nephropathy-a multicenter validation study. Kidney Blood Press Res. 2019;44:22–32. doi: 10.1159/000497808.
    1. Haas M, Verhave JC, Liu ZH, Alpers CE, Barratt J, Becker JU, et al. A multicenter study of the predictive value of crescents in IgA nephropathy. J Am Soc Nephrol. 2017;28:691–701. doi: 10.1681/ASN.2016040433.
    1. No authors. Chapter 10: Immunoglobulin A nephropathy. Kidney Int Suppl. 2012;2:209–17.
    1. Pozzi C, Bolasco PG, Fogazzi G, Andrulli S, Altieri P, Ponticelli C, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 1999;353:883–887. doi: 10.1016/S0140-6736(98)03563-6.
    1. Pozzi C, Andrulli S, Del Vecchio L, Melis P, Fogazzi GB, Altieri P, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol. 2004;15:157–163. doi: 10.1097/01.ASN.0000103869.08096.4F.
    1. Hotta O, Furuta T, Chiba S, Tomioka S, Taguma Y. Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis. 2002;39:493–502. doi: 10.1053/ajkd.2002.31399.
    1. Shoji T, Nakanishi I, Suzuki A, Hayashi T, Togawa M, Okada N, et al. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis. 2000;35:194–201. doi: 10.1016/S0272-6386(00)70326-X.
    1. Hou JH, Le WB, Chen N, Wang WM, Liu ZS, Liu D, et al. Mycophenolate Mofetil combined with prednisone versus full-dose prednisone in IgA nephropathy with active proliferative lesions: a randomized controlled trial. Am J Kidney Dis. 2017;69:788–795. doi: 10.1053/j.ajkd.2016.11.027.
    1. Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012;379:815–822. doi: 10.1016/S0140-6736(12)60033-6.
    1. Lee HS, Lee MS, Lee SM, Lee SY, Lee ES, Lee EY, et al. Histological grading of IgA nephropathy predicting renal outcome: revisiting H.S. Lee’s glomerular grading system. Nephrol Dial Transplant. 2005;20:342–348. doi: 10.1093/ndt/gfh633.
    1. Lin Y, Jia J, Guo Y, He D, Zhang Y, Wang F, et al. Corticosteroid for IgA nephropathy: are they really therapeutic? Am J Nephrol. 2018;47:385–394. doi: 10.1159/000489580.
    1. Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, et al. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med. 2015;373:2225–2236. doi: 10.1056/NEJMoa1415463.
    1. Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, et al. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA. 2017;318:432–442. doi: 10.1001/jama.2017.9362.
    1. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013;368:2402–2414. doi: 10.1056/NEJMra1206793.
    1. Chen J, Xu H, Peng Z, Lin L, Li C, Zhu X, et al. Efficacy of corticosteroids in immunoglobulin a nephropathy with less than 25% crescents. Clin Exp Nephrol. 2020;24:73–81. doi: 10.1007/s10157-019-01795-6.
    1. Pozzi C, Sarcina C, Ferrario F. Treatment of IgA nephropathy with renal insufficiency. J Nephrol. 2016;29:551–558. doi: 10.1007/s40620-015-0257-2.
    1. Chan HW, Cheung CY, Liu YL, Chan YH, Wong HS, Chak WL, et al. Prevalence of abnormal glucose metabolism in Chinese renal transplant recipients: a single Centre study. Nephrol Dial Transplant. 2008;23:3337–3342. doi: 10.1093/ndt/gfn246.
    1. Panthakalam S, Bhatnagar D, Klimiuk P. The prevalence and management of hyperglycaemia in patients with rheumatoid arthritis on corticosteroid therapy. Scott Med J. 2004;49:139–141. doi: 10.1177/003693300404900407.
    1. Gulliford MC, Charlton J, Latinovic R. Risk of diabetes associated with prescribed glucocorticoids in a large population. Diabetes Care. 2006;29:2728–2729. doi: 10.2337/dc06-1499.
    1. Valderhaug TG, Hjelmesæth J, Rollag H, Leivestad T, Røislien J, Jenssen T, et al. Reduced incidence of new-onset posttransplantation diabetes mellitus during the last decade. Transplantation. 2007;84:1125–1130. doi: 10.1097/01.tp.0000287191.45032.38.
    1. Calabrese Donihi A, Raval D, Saul M, Korytkowski MT, DeVita MA. Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients. Endocr Pract. 2006;12:358–362. doi: 10.4158/EP.12.4.358.
    1. Jeong Y, Han HS, Lee HD, Yang J, Jeong J, Choi MK, et al. A pilot study evaluating steroid-induced diabetes after antiemetic dexamethasone therapy in chemotherapy-treated cancer patients. Cancer Res Treat. 2016;48:1429–1437. doi: 10.4143/crt.2015.464.
    1. Rafacho A, Ortsäter H, Nadal A, Quesada I. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes. J Endocrinol. 2014;223:R49–R62. doi: 10.1530/JOE-14-0373.

Source: PubMed

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