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Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide

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Abstract

Background

The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial.

Methods

This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0 g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD.

Results

All patients were followed for a medial of 33.2 months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was − 4.5 (− 12.6, − 0.1) ml/min/1.73 m2 per year. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194–0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1–2), crescents present (C1–2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups.

Conclusion

Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.

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Acknowledgements

We thank the staff of the department of Nephrology, Xijing Hospital. This study was partially supported by grants from the National Natural Science Foundation of China (81670655), Key research and development plan of Shaanxi province, China (No. 2017ZDXM-SF-045). The discipline boosting program of the Xijing Hospital of the Fourth Military Medical University (XJZT18Z15). All the authors declared no competing interests.

Funding

This study was partially supported by grants from the National Natural Science Foundation of China (81670655), Key research and development plan of Shaanxi province, China (No. 2017ZDXM-SF-045). The discipline boosting program of the Xijing Hospital of the Fourth Military Medical University (XJZT18Z15).

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Author notes

  1. Feng Ma and Xiaoxia Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, No. 127 Changle West Road, Xi’an, 710032, Shaanxi Province, China

    Feng Ma, Xiaoxia Yang, Meilan Zhou, Ming Bai, Lijuan Zhao, Li Li, Ruijuan Dong, Chunmei Liu, Rong Li & Shiren Sun

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Contributions

FM and XXY designed the study, acquired data, interpreted data, drafted and revised the manuscript. MLZ, MB, LJZ and LL analyzed and interpreted data, drafted and revised the manuscript. RJD, CML and RL acquired data, interpreted data and revised the manuscript. SRS designed the study, revised the manuscript, assumed responsibility for the integrity of the data and supervised the research group. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shiren Sun.

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Ethical statement

The study was approved by the Ethics Committee of Xijing Hospital.  This study waived the requirement for written informed consent due to the retrospective nature of this study.  This study protocol was performed in accordance with the 1964 Declaration of Helsinki as well as the amendments or comparable ethical standards.

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Ma, F., Yang, X., Zhou, M. et al. Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide. J Nephrol 33, 1241–1250 (2020). https://doi.org/10.1007/s40620-020-00752-x

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