Skip to main content
Top
Published in: Clinical and Experimental Nephrology 6/2019

01-06-2019 | Original article

The beneficial effects of renin–angiotensin system inhibitors (RASI) on IgA nephropathy with tubulointerstitial lesions categorized by Oxford classification

Authors: Takahiro Kamiyama, Takahito Moriyama, Saeko Kumon, Kazunori Karasawa, Kosaku Nitta

Published in: Clinical and Experimental Nephrology | Issue 6/2019

Login to get access

Abstract

Background

Global sclerosis has been reported as the risk factor of IgAN. In Oxford classification, global sclerosis was correlated with tubulointerstitial (T) lesions. Therefore, in patients with T lesions, renin–angiotensin system inhibitors (RASI) might be effective by decreasing glomerular hyperfiltration and hypertension. However, these beneficial effects of RASI have not been reported.

Methods

In this retrospective cohort study, we divided 87 IgAN patients with T1/2 lesions into two groups: RASI group (n = 47, treated with RASI) and APA group (n = 40, treated with anti-platelet agents). We analyzed the background of each group, the serial changes of blood pressure and the amount of proteinuria (U-Prot), progression to end-stage renal disease, and the risk factors for progression.

Results

After propensity score matching, 22 cases from each group were selected, and clinical and histological characteristics were similar. Serial changes of blood pressure had been significantly decreased in RASI group (p = 0.0029), but not in the APA group. Proteinuria was tended to decrease in RASI group, though it was not significant (1.14–0.47 g/gCre) and it was similar in APA group (0.95–0.85 g/gCre). 20 year renal survival rate was 59.5% in RASI group, whereas 21.3% in APA group (p = 0.0119). In multivariate Cox regression analysis, RASI was an independent factor to prevent from progression to ESRD (HR 5.91, p = 0.0039).

Conclusion

RASI has shown a significant beneficial effect on histologically advanced IgAN patients with T lesions. These results are compatible with the previous studies that reported the beneficial effects of RASI on clinically advanced IgAN patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant. 2011;26:414–30.CrossRefPubMed McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant. 2011;26:414–30.CrossRefPubMed
2.
go back to reference Berger J, Hinglais N. Intercapillary deposits of IgA–IgG. J Urol Nephrol (Paris). 1968;74:694–5. Berger J, Hinglais N. Intercapillary deposits of IgA–IgG. J Urol Nephrol (Paris). 1968;74:694–5.
3.
go back to reference D’Amico G. Clinical features and natural history in adults with IgA nephropathy. Am J Kidney Dis. 1988;12:353–7.CrossRefPubMed D’Amico G. Clinical features and natural history in adults with IgA nephropathy. Am J Kidney Dis. 1988;12:353–7.CrossRefPubMed
4.
go back to reference Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol. 2002;13:142–8.PubMed Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol. 2002;13:142–8.PubMed
5.
go back to reference Rekola S, Bergstrand A, Bucht H. IGA nephropathy: a retrospective evaluation of prognostic indices in 176 patients. Scand J Urol Nephrol. 1989;23:37–50.CrossRefPubMed Rekola S, Bergstrand A, Bucht H. IGA nephropathy: a retrospective evaluation of prognostic indices in 176 patients. Scand J Urol Nephrol. 1989;23:37–50.CrossRefPubMed
6.
go back to reference Freese P, Norden G, Nyberg G. Morphologic high-risk factors in IgA nephropathy. Nephron. 1998;79:420–5.CrossRefPubMed Freese P, Norden G, Nyberg G. Morphologic high-risk factors in IgA nephropathy. Nephron. 1998;79:420–5.CrossRefPubMed
7.
go back to reference Hogg RJ, Silva FG, Wyatt RJ, Reisch JS, Argyle JC, Savino DA. Prognostic indicators in children with IgA nephropathy-report of the Southwest Pediatric Nephrology Study Group. Pediatr Nephrol. 1994;8:15–20.CrossRefPubMed Hogg RJ, Silva FG, Wyatt RJ, Reisch JS, Argyle JC, Savino DA. Prognostic indicators in children with IgA nephropathy-report of the Southwest Pediatric Nephrology Study Group. Pediatr Nephrol. 1994;8:15–20.CrossRefPubMed
8.
go back to reference Boyce NW, Holdsworth SR, Thomson NM, Atkins RC. Clinicopathological associations in mesangial IgA nephropathy. Am J Nephrol. 1986;6:246–52.CrossRefPubMed Boyce NW, Holdsworth SR, Thomson NM, Atkins RC. Clinicopathological associations in mesangial IgA nephropathy. Am J Nephrol. 1986;6:246–52.CrossRefPubMed
9.
go back to reference Katafuchi R, Oh Y, Hori K, Komota T, Yanase T, Ikeda K, et al. An important role of glomerular segmental lesions on progression of IgA nephropathy: a multivariate analysis. Clin Nephrol. 1994;41:191–8.PubMed Katafuchi R, Oh Y, Hori K, Komota T, Yanase T, Ikeda K, et al. An important role of glomerular segmental lesions on progression of IgA nephropathy: a multivariate analysis. Clin Nephrol. 1994;41:191–8.PubMed
10.
go back to reference Ibels LS, Gyory AZ. IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (Baltimore). 1994;73:79–102.CrossRef Ibels LS, Gyory AZ. IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (Baltimore). 1994;73:79–102.CrossRef
11.
go back to reference To KF, Choi PC, Szeto CC, Li PK, Tang NL, Leung CB, et al. Outcome of IgA nephropathy in adults graded by chronic histological lesions. Am J Kidney Dis. 2000;35:392–400.CrossRefPubMed To KF, Choi PC, Szeto CC, Li PK, Tang NL, Leung CB, et al. Outcome of IgA nephropathy in adults graded by chronic histological lesions. Am J Kidney Dis. 2000;35:392–400.CrossRefPubMed
12.
go back to reference Okada H, Suzuki H, Konishi K, Sakaguchi H, Saruta T. Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy. Clin Nephrol. 1992;37:235–8.PubMed Okada H, Suzuki H, Konishi K, Sakaguchi H, Saruta T. Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy. Clin Nephrol. 1992;37:235–8.PubMed
13.
go back to reference D’Amico G, Minetti L, Ponticelli C, Fellin G, Ferrario F, di Belgioioso BG, et al. Prognostic indicators in idiopathic IgA mesangial nephropathy. Q J Med. 1986;59:363–78.PubMed D’Amico G, Minetti L, Ponticelli C, Fellin G, Ferrario F, di Belgioioso BG, et al. Prognostic indicators in idiopathic IgA mesangial nephropathy. Q J Med. 1986;59:363–78.PubMed
14.
go back to reference Nozawa R, Suzuki J, Takahashi A, Isome M, Kawasaki Y, Suzuki S, et al. Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation. Clin Nephrol. 2005;64:171–9.CrossRefPubMed Nozawa R, Suzuki J, Takahashi A, Isome M, Kawasaki Y, Suzuki S, et al. Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation. Clin Nephrol. 2005;64:171–9.CrossRefPubMed
15.
go back to reference Mera J, Uchida S, Nagase M. Clinicopathologic study on prognostic markers in IgA nephropathy. Nephron. 2000;84:148–57.CrossRefPubMed Mera J, Uchida S, Nagase M. Clinicopathologic study on prognostic markers in IgA nephropathy. Nephron. 2000;84:148–57.CrossRefPubMed
16.
go back to reference Daniel L, Saingra Y, Giorgi R, Bouvier C, Pellissier JF, Berland Y. Tubular lesions determine prognosis of IgA nephropathy. Am J Kidney Dis. 2000;35:13–20.CrossRefPubMed Daniel L, Saingra Y, Giorgi R, Bouvier C, Pellissier JF, Berland Y. Tubular lesions determine prognosis of IgA nephropathy. Am J Kidney Dis. 2000;35:13–20.CrossRefPubMed
17.
go back to reference Vleming LJ, de Fijter JW, Westendorp RG, Daha MR, Bruijn JA, van Es LA. Histomorphometric correlates of renal failure in IgA nephropathy. Clin Nephrol. 1998;49:337–44.PubMed Vleming LJ, de Fijter JW, Westendorp RG, Daha MR, Bruijn JA, van Es LA. Histomorphometric correlates of renal failure in IgA nephropathy. Clin Nephrol. 1998;49:337–44.PubMed
18.
go back to reference Bogenschutz O, Bohle A, Batz C, Wehrmann M, Pressler H, Kendziorra H, et al. IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients. Am J Nephrol. 1990;10:137–47.CrossRefPubMed Bogenschutz O, Bohle A, Batz C, Wehrmann M, Pressler H, Kendziorra H, et al. IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients. Am J Nephrol. 1990;10:137–47.CrossRefPubMed
19.
go back to reference Working Group of the International Ig ANN, The Renal Pathology S, Roberts IS, Cook HT, Troyanov S, Alpers CE, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56.CrossRef Working Group of the International Ig ANN, The Renal Pathology S, Roberts IS, Cook HT, Troyanov S, Alpers CE, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56.CrossRef
20.
go back to reference Working Group of the International Ig ANN, The Renal Pathology S, Cattran DC, Coppo R, Cook HT, Feehally J, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76:534–45.CrossRef Working Group of the International Ig ANN, The Renal Pathology S, Cattran DC, Coppo R, Cook HT, Feehally J, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76:534–45.CrossRef
21.
go back to reference Hisano S, Joh K, Katafuchi R, Shimizu A, Hashiguchi N, Kawamura T, et al. Reproducibility for pathological prognostic parameters of the Oxford classification of IgA nephropathy: a Japanese cohort study of the Ministry of Health, Labor and Welfare. Clin Exp Nephrol. 2017;21:92–6.CrossRefPubMed Hisano S, Joh K, Katafuchi R, Shimizu A, Hashiguchi N, Kawamura T, et al. Reproducibility for pathological prognostic parameters of the Oxford classification of IgA nephropathy: a Japanese cohort study of the Ministry of Health, Labor and Welfare. Clin Exp Nephrol. 2017;21:92–6.CrossRefPubMed
22.
go back to reference 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(5):1014–21.CrossRefPubMed 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(5):1014–21.CrossRefPubMed
23.
go back to reference Lv J, Shi S, Xu D, Zhang H, Troyanov S, Cattran DC, et al. Evaluation of the Oxford Classification of IgA nephropathy: a systematic review and meta-analysis. Am J Kidney Dis. 2013;62:891–9.CrossRefPubMed Lv J, Shi S, Xu D, Zhang H, Troyanov S, Cattran DC, et al. Evaluation of the Oxford Classification of IgA nephropathy: a systematic review and meta-analysis. Am J Kidney Dis. 2013;62:891–9.CrossRefPubMed
24.
go back to reference Kaihan AB, Yasuda Y, Katsuno T, Kato S, Imaizumi T, Ozeki T, et al. The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients. Clin Exp Nephrol. 2017;21:986–94.CrossRefPubMed Kaihan AB, Yasuda Y, Katsuno T, Kato S, Imaizumi T, Ozeki T, et al. The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients. Clin Exp Nephrol. 2017;21:986–94.CrossRefPubMed
25.
go back to reference Praga M, Gutierrez E, Gonzalez E, Morales E, Hernandez E. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol. 2003;14:1578–83.CrossRef Praga M, Gutierrez E, Gonzalez E, Morales E, Hernandez E. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol. 2003;14:1578–83.CrossRef
26.
go back to reference Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, et al. Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy. Am J Nephrol. 2000;20:373–9.CrossRefPubMed Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, et al. Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy. Am J Nephrol. 2000;20:373–9.CrossRefPubMed
27.
go back to reference Tanaka S, Ninomiya T, Katafuchi R, Masutani K, Nagata M, Tsuchimoto A, et al. The effect of renin–angiotensin system blockade on the incidence of end-stage renal disease in IgA nephropathy. Clin Exp Nephrol. 2016;20:689–98.CrossRefPubMed Tanaka S, Ninomiya T, Katafuchi R, Masutani K, Nagata M, Tsuchimoto A, et al. The effect of renin–angiotensin system blockade on the incidence of end-stage renal disease in IgA nephropathy. Clin Exp Nephrol. 2016;20:689–98.CrossRefPubMed
28.
go back to reference Hotta O. Use of corticosteroids, other immunosuppressive therapies, and tonsillectomy in the treatment of IgA nephropathy. Semin Nephrol. 2004;24:244–55.CrossRefPubMed Hotta O. Use of corticosteroids, other immunosuppressive therapies, and tonsillectomy in the treatment of IgA nephropathy. Semin Nephrol. 2004;24:244–55.CrossRefPubMed
29.
go back to reference Zou Y, Yang M, Du X. New insight into the management of IgA nephropathy. Clin Exp Nephrol. 2018;22:1442–3.CrossRefPubMed Zou Y, Yang M, Du X. New insight into the management of IgA nephropathy. Clin Exp Nephrol. 2018;22:1442–3.CrossRefPubMed
30.
go back to reference Moriyama T, Amemiya N, Ochi A, Tsuruta Y, Shimizu A, Itabashi M, et al. Comparison of steroids and angiotensin receptor blockers for patients with advanced IgA nephropathy and impaired renal function. Am J Nephrol. 2011;34:233–40.CrossRefPubMed Moriyama T, Amemiya N, Ochi A, Tsuruta Y, Shimizu A, Itabashi M, et al. Comparison of steroids and angiotensin receptor blockers for patients with advanced IgA nephropathy and impaired renal function. Am J Nephrol. 2011;34:233–40.CrossRefPubMed
31.
32.
go back to reference Moriyama T, Amamiya N, Ochi A, Tsuruta Y, Shimizu A, Kojima C, et al. Long-term beneficial effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy for patients with advanced immunoglobulin A nephropathy and impaired renal function. Clin Exp Nephrol. 2011;15:700–7.CrossRefPubMed Moriyama T, Amamiya N, Ochi A, Tsuruta Y, Shimizu A, Kojima C, et al. Long-term beneficial effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy for patients with advanced immunoglobulin A nephropathy and impaired renal function. Clin Exp Nephrol. 2011;15:700–7.CrossRefPubMed
33.
go back to reference Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Investig. 1986;77:1993–2000.CrossRefPubMed Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Investig. 1986;77:1993–2000.CrossRefPubMed
34.
go back to reference Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 2000;57:1803–17.CrossRef Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 2000;57:1803–17.CrossRef
35.
go back to reference Okabayashi Y, Tsuboi N, Haruhara K, Kanzaki G, Koike K, Shimizu A, et al. Reduction of proteinuria by therapeutic intervention improves the renal outcome of elderly patients with IgA nephropathy. Clin Exp Nephrol. 2016;20:910–7.CrossRefPubMed Okabayashi Y, Tsuboi N, Haruhara K, Kanzaki G, Koike K, Shimizu A, et al. Reduction of proteinuria by therapeutic intervention improves the renal outcome of elderly patients with IgA nephropathy. Clin Exp Nephrol. 2016;20:910–7.CrossRefPubMed
Metadata
Title
The beneficial effects of renin–angiotensin system inhibitors (RASI) on IgA nephropathy with tubulointerstitial lesions categorized by Oxford classification
Authors
Takahiro Kamiyama
Takahito Moriyama
Saeko Kumon
Kazunori Karasawa
Kosaku Nitta
Publication date
01-06-2019
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 6/2019
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-019-01713-w

Other articles of this Issue 6/2019

Clinical and Experimental Nephrology 6/2019 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 discuss last year's major advances in heart failure and cardiomyopathies.