Abstract
IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The classic manifestation of IgAN is episodic hematuria and proteinuria. Nephrotic syndrome (NS) is not very common in IgAN, reported to occur in only 5–10% of IgAN patients. However, the clinical and pathological characteristics and long-term outcomes of patients with NS-IgAN at onset remain unknown. A retrospective study was conducted, enrolling 1165 patients with biopsy-proven IgAN from West China Hospital in 2008–2015. Patients with renal biopsy of minimal change disease with mesangial IgA deposits were excluded. The renal endpoint was defined as 50% decrease in eGFR or progressing into end-stage renal disease (ESRD). A total of 1165 patients were enrolled with average age of 34.58, and 171 (14.7%) patients were presented with NS. Comparing NS and non-NS groups, significance differences were shown in hypertension (HTN), 24-h urine protein, serum albumin, serum creatine, eGFR and uric acid. NS group had severe pathological changes such as endocapillary hypercellularity, tubular atrophy or interstitial fibrosis and crescent, but less segmental glomerulosclerosis or adhesion and global sclerosis. During the average follow-up of 44.27 months, 29.8% (51/171) NS patients and 15.8% (157/994) non-NS patients progressed to the renal endpoint. 5-year renal survival rates were 73.1% and 87.8% (P < 0.001) in NS and non-NS groups, respectively. This study demonstrated that IgAN patients with NS had higher serum creatine, lower eGFR, lower uric acid, more acute lesions and poor prognosis. NS was an independent risk factor for progression to the renal endpoint.
Similar content being viewed by others
References
Berger J, Hinglais N. Intercapillary deposits of IgA-IgG. Journal d’urologie et de nephrologie. 1968;74(9):694–5.
Manno C, Strippoli GF, D’Altri C, Torres D, Rossini M, Schena FP. A novel simpler histological classification for renal survival in IgA nephropathy: a retrospective study. Am J Kidney Dis. 2007;49(6):763–75. https://doi.org/10.1053/j.ajkd.2007.03.013.
Kim JK, Kim JH, Lee SC, Kang EW, Chang TI, Moon SJ, et al. Clinical features and outcomes of IgA nephropathy with nephrotic syndrome. Clin J Am Soc Nephrol CJASN. 2012;7(3):427–36. https://doi.org/10.2215/CJN.04820511.
Donadio JV, Bergstralh EJ, Grande JP, Rademcher DM. Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy. Nephrol Dial Transpl. 2002;17(7):1197–203.
Beck L, Bomback AS, Choi MJ, Holzman LB, Langford C, Mariani LH, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. Am J Kidney Dis. 2013;62(3):403–41. https://doi.org/10.1053/j.ajkd.2013.06.002.
Han SH, Kang EW, Park JK, Kie JH, Han DS, Kang SW. Spontaneous remission of nephrotic syndrome in patients with IgA nephropathy. Nephrol Dial Transpl. 2011;26(5):1570–5. https://doi.org/10.1093/ndt/gfq559.
Wang J, Juan C, Huang Q, Zeng C, Liu Z. Corticosteroid therapy in IgA nephropathy with minimal change-like lesions: a single-centre cohort study. Nephrol Dial Transpl. 2013;28(9):2339–45. https://doi.org/10.1093/ndt/gft211.
Qin J, Yang Q, Tang X, Chen W, Li Z, Mao H, et al. Clinicopathologic features and treatment response in nephrotic IgA nephropathy with minimal change disease. Clin Nephrol. 2013;79(1):37–44. https://doi.org/10.5414/cn107682.
Li XW, Liang SS, Le WB, Cheng SQ, Zeng CH, Wang JQ, et al. Long-term outcome of IgA nephropathy with minimal change disease: a comparison between patients with and without minimal change disease. J Nephrol. 2016;29(4):567–73. https://doi.org/10.1007/s40620-015-0242-9.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.
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(5):534–45. https://doi.org/10.1038/ki.2009.243.
Roberts ISD, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76(5):546–56. https://doi.org/10.1038/ki.2009.168.
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 JASN. 2017;28(2):691–701. https://doi.org/10.1681/asn.2016040433.
Shima Y, Nakanishi K. IgA nephropathy with presentation of nephrotic syndrome at onset in children. Pediatr Nephrol. 2017;32(3):457–65. https://doi.org/10.1007/s00467-016-3502-6.
Kim SM, Moon KC, Oh KH, Joo KW, Kim YS, Ahn C, et al. Clinicopathologic characteristics of IgA nephropathy with steroid-responsive nephrotic syndrome. J Korean Med Sci. 2009;24(Suppl):S44–9. https://doi.org/10.3346/jkms.2009.24.S1.S44.
Lai KN, Lai FM, Ho CP, Chan KW. Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. Clin Nephrol. 1986;26(4):174–80.
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(23):2225–36. https://doi.org/10.1056/NEJMoa1415463.
D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64(245):709–27.
Geddes CC, Rauta V, Gronhagen-Riska C, Bartosik LP, Jardine AG, Ibels LS, et al. A tricontinental view of IgA nephropathy. Nephrol Dial Transpl. 2003;18(8):1541–8.
Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002;347(10):738–48. https://doi.org/10.1056/NEJMra020109.
Suliman ME, Johnson RJ, Garcia-Lopez E, Qureshi AR, Molinaei H, Carrero JJ, et al. J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis. 2006;48(5):761–71. https://doi.org/10.1053/j.ajkd.2006.08.019.
Matsukuma Y, Masutani K, Tanaka S, Tsuchimoto A, Fujisaki K, Torisu K, et al. A J-shaped association between serum uric acid levels and poor renal survival in female patients with IgA nephropathy. Hypertens Res. 2017;40(3):291–7. https://doi.org/10.1038/hr.2016.134.
Fathallah-Shaykh SA, Cramer MT. Uric acid and the kidney. Pediatr Nephrol. 2013;29(6):999–1008. https://doi.org/10.1007/s00467-013-2549-x.
Soares MF, Roberts IS. IgA nephropathy: an update. Curr Opin Nephrol Hypertens. 2017;26(3):165–71. https://doi.org/10.1097/mnh.0000000000000312.
Kawamura T, Joh K, Okonogi H, Koike K, Utsunomiya Y, Miyazaki Y, et al. A histologic classification of IgA nephropathy for predicting long-term prognosis: emphasis on end-stage renal disease. J Nephrol. 2013;26(2):350–7. https://doi.org/10.5301/jn.5000151.
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(1):92–6. https://doi.org/10.1007/s10157-016-1258-8.
Zhang L, Li J, Yang S, Huang N, Zhou Q, Yang Q, et al. Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury. Ren Fail. 2016;38(5):799–805. https://doi.org/10.3109/0886022x.2016.1163153.
Wakai K, Kawamura T, Endoh M, Kojima M, Tomino Y, Tamakoshi A, et al. A scoring system to predict renal outcome in IgA nephropathy: from a nationwide prospective study. Nephrol Dial Transpl. 2006;21(10):2800–8. https://doi.org/10.1093/ndt/gfl342.
Goto M, Wakai K, Kawamura T, Ando M, Endoh M, Tomino Y. A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10-year prospective cohort study. Nephrol Dial Transpl. 2009;24(10):3068–74. https://doi.org/10.1093/ndt/gfp273.
Reich HN, Troyanov S, Scholey JW, Cattran DC. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol JASN. 2007;18(12):3177–83. https://doi.org/10.1681/asn.2007050526.
Tan L, Tang Y, Peng W, Mathew Bechu S, Qin W. Combined immunosuppressive treatment may improve short-term renal outcomes in Chinese patients with advanced iga nephropathy. Kidney Blood Press Res. 2018;43:1333–43. https://doi.org/10.1159/000492592.
Wang Y, Tian J, Guo H, Mi Y, Zhang R, Li R. Intermedin ameliorates IgA nephropathy by inhibition of oxidative stress and inflammation. Clin Exp Med. 2016;16(2):183–92. https://doi.org/10.1007/s10238-015-0351-8.
Acknowledgements
The authors thank all of the participants and attending physicians for their contributions.
Funding
None.
Author information
Authors and Affiliations
Contributions
XH, YT and WQ conceived and designed the study. YT and WQ provided the administrative support. XH, YX, XZ and MA collected and assembled the data. XH, YX and XZ analyzed and interpreted the data. All authors participated in manuscript writing and gave final approval for the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical standards
The research was in compliance with the Declaration of Helsinki and was approved by the ethical committee of West China Hospital of Sichuan University.
Statement of ethics
The authors have no ethical conflicts to disclose.
Informed consent
Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Han, X., Xiao, Y., Tang, Y. et al. Clinical and pathological features of immunoglobulin A nephropathy patients with nephrotic syndrome. Clin Exp Med 19, 479–486 (2019). https://doi.org/10.1007/s10238-019-00580-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10238-019-00580-9