Skip to main content
Top
Published in: Clinical and Experimental Nephrology 10/2020

01-10-2020 | Original article

Efficacy of corticosteroid therapy for IgA nephropathy patients stratified by kidney function and proteinuria

Authors: Yasuyuki Nagasawa, Ryohei Yamamoto, Maki Shinzawa, Tatsuya Shoji, Yukiko Hasuike, Katsuyuki Nagatoya, Atsushi Yamauchi, Terumasa Hayashi, Takayuki Kuragano, Toshiki Moriyama, Yoshitaka Isaka

Published in: Clinical and Experimental Nephrology | Issue 10/2020

Login to get access

Abstract

Background

Steroid therapy is one of the important therapies for IgA nephropathy (IgAN), but the features of the IgAN patients who have the benefit from this therapy remained unclear.

Methods

This retrospective observational study, using data of 874 patients with IgAN analyzed the proteinuria and kidney function of IgAN patients who had beneficial effect by steroid therapy. Two advantages of the present study were a large cohort and a long observational period.

Results

Corticosteroid therapy had ameliorated the kidney prognosis [incident rate ratio (IRR) 0.57 (95%CI 0.34–0.92), P = 0.029]. Because of interaction between kidney function and use of corticosteroid (P = 0.047), stratification analysis by kidney function revealed that prognosis of kidney function in IgAN patients whose eGFR was less than 60 ml/min/1.73m2 was ameliorated by corticosteroid therapy [IRR 0.50 (95%CI 0.26–0.97), P = 0.015); while, there was no change of kidney prognosis in IgAN patients whose eGFR was above 60 ml/min/1.73 m2. To make the target of corticosteroid therapy for IgAN patients more clear, IgAN patients, whose eGFR were less than 60 ml/min/1.73 m2, were stratified by proteinuria (1 g/day). In IgAN patients whose eGFR were under 60 ml/min/1.73 m2 and whose proteinuria were over 1.0 g/day, corticosteroid therapy seemed to ameliorate kidney function [IRR 0.39 (95%CI 0.19–0.86), P < 0.05]; while, there was obviously no change by corticosteroid therapy in IgAN patients whose eGFR were less than 60 ml/min/1.73 m2 and whose proteinuria were less than 1.0 g/day.

Conclusion

Our results suggested that steroid therapy was especially effective for IgAN patients whose eGFR was less than 60 ml/min/1.73 m2 and whose proteinuria was more than 1.0 g/day.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Moriyama T, Tanaka K, Iwasaki C, Oshima Y, Ochi A, Kataoka H, et al. Prognosis in IgA nephropathy: 30-year analysis of 1,012 patients at a single center in Japan. PLoS ONE. 2014;9:e91756.CrossRef Moriyama T, Tanaka K, Iwasaki C, Oshima Y, Ochi A, Kataoka H, et al. Prognosis in IgA nephropathy: 30-year analysis of 1,012 patients at a single center in Japan. PLoS ONE. 2014;9:e91756.CrossRef
3.
go back to reference Yamamoto R, Nagasawa Y, Shoji T, Katakami N, Ohtoshi K, Hayaishi-Okano R, et al. A candidate gene approach to genetic contributors to the development of IgA nephropathy. Nephrol Dial Transplant. 2012;27:1020–30.CrossRef Yamamoto R, Nagasawa Y, Shoji T, Katakami N, Ohtoshi K, Hayaishi-Okano R, et al. A candidate gene approach to genetic contributors to the development of IgA nephropathy. Nephrol Dial Transplant. 2012;27:1020–30.CrossRef
4.
go back to reference Kiryluk K, Novak J, Gharavi AG. Pathogenesis of immunoglobulin A nephropathy: recent insight from genetic studies. Annu Rev Med. 2013;64:339–56.CrossRef Kiryluk K, Novak J, Gharavi AG. Pathogenesis of immunoglobulin A nephropathy: recent insight from genetic studies. Annu Rev Med. 2013;64:339–56.CrossRef
5.
go back to reference Coppo R, Amore A, Peruzzi L, Vergano L, Camilla R. Innate immunity and IgA nephropathy. J Nephrol. 2010;23:626–32.PubMed Coppo R, Amore A, Peruzzi L, Vergano L, Camilla R. Innate immunity and IgA nephropathy. J Nephrol. 2010;23:626–32.PubMed
6.
go back to reference Iwatani H, Nagasawa Y, Yamamoto R, Iio K, Mizui M, Horii A, et al. CD16CD56 cells are a potential culprit for hematuria in IgA nephropathy. Clin Exp Nephrol. 2014;19:216–24.CrossRef Iwatani H, Nagasawa Y, Yamamoto R, Iio K, Mizui M, Horii A, et al. CD16CD56 cells are a potential culprit for hematuria in IgA nephropathy. Clin Exp Nephrol. 2014;19:216–24.CrossRef
7.
go back to reference Iio K, Nagasawa Y, Iwatani H, Yamamoto R, Horii A, Okuzaki D, et al. Microarray analysis of tonsils in immunoglobulin. A nephropathy patients. Biochem Biophys Res Commun. 2010;393:565–70.CrossRef Iio K, Nagasawa Y, Iwatani H, Yamamoto R, Horii A, Okuzaki D, et al. Microarray analysis of tonsils in immunoglobulin. A nephropathy patients. Biochem Biophys Res Commun. 2010;393:565–70.CrossRef
8.
go back to reference Nagasawa Y, Okuzaki D, Muso E, Yamamoto R, Shinzawa M, Iwasaki Y, et al. IFI27 Is a useful genetic marker for diagnosis of immunoglobulin a nephropathy and membranous nephropathy using peripheral blood. PLoS ONE. 2016;11:e0153252.CrossRef Nagasawa Y, Okuzaki D, Muso E, Yamamoto R, Shinzawa M, Iwasaki Y, et al. IFI27 Is a useful genetic marker for diagnosis of immunoglobulin a nephropathy and membranous nephropathy using peripheral blood. PLoS ONE. 2016;11:e0153252.CrossRef
9.
go back to reference Suzuki S, Nakatomi Y, Sato H, Tsukada H, Arakawa M. Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy. Lancet. 1994;343:12–6.CrossRef Suzuki S, Nakatomi Y, Sato H, Tsukada H, Arakawa M. Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy. Lancet. 1994;343:12–6.CrossRef
10.
go back to reference Nagasawa Y, Iio K, Fukuda S, Date Y, Iwatani H, Yamamoto R, et al. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment. PLoS ONE. 2014;9:e81636.CrossRef Nagasawa Y, Iio K, Fukuda S, Date Y, Iwatani H, Yamamoto R, et al. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment. PLoS ONE. 2014;9:e81636.CrossRef
11.
go back to reference Misaki T, Naka S, Kuroda K, Nomura R, Shiooka T, Naito Y, et al. Distribution of Streptococcus mutans strains with collagen-binding proteins in the oral cavity of IgA nephropathy patients. Clin Exp Nephrol. 2015;19:844–50.CrossRef Misaki T, Naka S, Kuroda K, Nomura R, Shiooka T, Naito Y, et al. Distribution of Streptococcus mutans strains with collagen-binding proteins in the oral cavity of IgA nephropathy patients. Clin Exp Nephrol. 2015;19:844–50.CrossRef
12.
go back to reference Misaki T, Naka S, Hatakeyama R, Fukunaga A, Nomura R, Isozaki T, et al. Presence of Streptococcus mutans strains harbouring the cnm gene correlates with dental caries status and IgA nephropathy conditions. Sci Rep. 2016;6:36455.CrossRef Misaki T, Naka S, Hatakeyama R, Fukunaga A, Nomura R, Isozaki T, et al. Presence of Streptococcus mutans strains harbouring the cnm gene correlates with dental caries status and IgA nephropathy conditions. Sci Rep. 2016;6:36455.CrossRef
13.
go back to reference Misaki T, Naka S, Wato K, Hatakeyama R, Nagasawa Y, Ito S, et al. Campylobacter rectus in the oral cavity correlates with proteinuria in immunoglobulin. A Nephropathy Patients. Nephron. 2018;139:143–9.CrossRef Misaki T, Naka S, Wato K, Hatakeyama R, Nagasawa Y, Ito S, et al. Campylobacter rectus in the oral cavity correlates with proteinuria in immunoglobulin. A Nephropathy Patients. Nephron. 2018;139:143–9.CrossRef
14.
go back to reference Nagasawa Y, Yamamoto R, Rakugi H, Isaka Y. Cigarette smoking and chronic kidney diseases. Hypertens Res. 2012;35:261–5.CrossRef Nagasawa Y, Yamamoto R, Rakugi H, Isaka Y. Cigarette smoking and chronic kidney diseases. Hypertens Res. 2012;35:261–5.CrossRef
15.
go back to reference Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Hamano T, Kawada N, et al. Cigarette smoking and progression of IgA nephropathy. Am J Kidney Dis. 2010;56:313–24.CrossRef Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Hamano T, Kawada N, et al. Cigarette smoking and progression of IgA nephropathy. Am J Kidney Dis. 2010;56:313–24.CrossRef
16.
go back to reference Syrjanen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant. 2000;15:34–42.CrossRef Syrjanen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant. 2000;15:34–42.CrossRef
17.
go back to reference Nagasawa Y, Yamamoto R, Shoji T, Shinzawa M, Hasuike Y, Nagatoya K, et al. Serum uric acid level predicts progression of iga nephropathy in females but not in males. PLoS ONE. 2016;11:e0160828.CrossRef Nagasawa Y, Yamamoto R, Shoji T, Shinzawa M, Hasuike Y, Nagatoya K, et al. Serum uric acid level predicts progression of iga nephropathy in females but not in males. PLoS ONE. 2016;11:e0160828.CrossRef
18.
go back to reference Yamamoto R, Nagasawa Y, Shoji T, Inoue K, Uehata T, Kaneko T, et al. A candidate gene approach to genetic prognostic factors of IgA nephropathy–a result of polymorphism research to DIstinguish genetic factors contributing to progression of iga nephropathy (PREDICT-IgAN). Nephrol Dial Transplant. 2009;1:7. Yamamoto R, Nagasawa Y, Shoji T, Inoue K, Uehata T, Kaneko T, et al. A candidate gene approach to genetic prognostic factors of IgA nephropathy–a result of polymorphism research to DIstinguish genetic factors contributing to progression of iga nephropathy (PREDICT-IgAN). Nephrol Dial Transplant. 2009;1:7.
19.
go back to reference Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 2012;8:e1002765.CrossRef Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 2012;8:e1002765.CrossRef
20.
go back to reference Teranishi J, Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Okada N, et al. ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy. J Renin Angiotensin Aldosterone Syst. 2015;16:633–41.CrossRef Teranishi J, Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Okada N, et al. ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy. J Renin Angiotensin Aldosterone Syst. 2015;16:633–41.CrossRef
21.
go back to reference Lin C, Yang HY, Wu CC, Lee HS, Lin YF, Lu KC, et al. Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension–a meta-regression analysis of 98 observational studies. PLoS ONE. 2014;9:e87604.CrossRef Lin C, Yang HY, Wu CC, Lee HS, Lin YF, Lu KC, et al. Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension–a meta-regression analysis of 98 observational studies. PLoS ONE. 2014;9:e87604.CrossRef
22.
go back to reference Manno C, Torres DD, Rossini M, Pesce F, Schena FP. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant. 2009;24:3694–701.CrossRef Manno C, Torres DD, Rossini M, Pesce F, Schena FP. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant. 2009;24:3694–701.CrossRef
23.
go back to reference Lv J, Zhang H, Chen Y, Li G, Jiang L, Singh AK, et al. Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis. 2009;53:26–322.CrossRef Lv J, Zhang H, Chen Y, Li G, Jiang L, Singh AK, et al. Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis. 2009;53:26–322.CrossRef
24.
go back to reference Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 1999;353:883–7.CrossRef Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 1999;353:883–7.CrossRef
25.
go back to reference 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;15:157–63.CrossRef 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;15:157–63.CrossRef
26.
go back to reference 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;373:2225–36.CrossRef 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;373:2225–36.CrossRef
27.
go back to reference Lv J, Xu D, Perkovic V, Ma X, Johnson DW, Woodward M, et al. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012;23:1108–16.CrossRef Lv J, Xu D, Perkovic V, Ma X, Johnson DW, Woodward M, et al. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012;23:1108–16.CrossRef
28.
go back to reference Hsu CY. In patients with proteinuric IgA nephropathy benefits of methylprednisolone were offset by harms. Ann Intern Med. 2017;167:58.CrossRef Hsu CY. In patients with proteinuric IgA nephropathy benefits of methylprednisolone were offset by harms. Ann Intern Med. 2017;167:58.CrossRef
29.
go back to reference 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;318:432–42.CrossRef 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;318:432–42.CrossRef
30.
go back to reference Miyawaki Y, Katsuyama T, Sada KE, Hiramatsu S, Ohashi K, Morishita M, et al. A retrospective observational study of glucocorticoid-induced diabetes mellitus with IgA nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy. PLoS ONE. 2017;12:e0178018.CrossRef Miyawaki Y, Katsuyama T, Sada KE, Hiramatsu S, Ohashi K, Morishita M, et al. A retrospective observational study of glucocorticoid-induced diabetes mellitus with IgA nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy. PLoS ONE. 2017;12:e0178018.CrossRef
31.
go back to reference Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRef Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRef
32.
go back to reference Tesar V, Troyanov S, Bellur S, Verhave JC, Cook HT, Feehally J, et al. Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study. J Am Soc Nephrol. 2015;26:2248–58.CrossRef Tesar V, Troyanov S, Bellur S, Verhave JC, Cook HT, Feehally J, et al. Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study. J Am Soc Nephrol. 2015;26:2248–58.CrossRef
Metadata
Title
Efficacy of corticosteroid therapy for IgA nephropathy patients stratified by kidney function and proteinuria
Authors
Yasuyuki Nagasawa
Ryohei Yamamoto
Maki Shinzawa
Tatsuya Shoji
Yukiko Hasuike
Katsuyuki Nagatoya
Atsushi Yamauchi
Terumasa Hayashi
Takayuki Kuragano
Toshiki Moriyama
Yoshitaka Isaka
Publication date
01-10-2020
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 10/2020
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-020-01918-4

Other articles of this Issue 10/2020

Clinical and Experimental Nephrology 10/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.