Clinical evaluation of strengthening spleen and draining dampness in the treatment of idiopathic membranous nephropathy: a retrospective 10-year follow-up study

doi:10.19852/j.cnki.jtcm.2025.04.018

Abstract

Abstract:

OBJECTIVE: To evaluate the 10-year therapeutic efficacy of Traditional Chinese Medicine (TCM) using the Strengthening Spleen and Draining Dampness therapy in the management of idiopathic membranous nephropathy (IMN).

METHODS: A single-center, retrospective analysis was conducted on patients diagnosed with IMN who met predefined inclusion and exclusion criteria. Data were collected from the Department of Nephrology at Longhua Hospital, affiliated with Shanghai University of Traditional Chinese Medicine, between January 2007 and December 2011. Clinical parameters including 24-h urinary protein, serum albumin, serum creatinine, and estimated glomerular filtration rate (eGFR, EPI) were assessed at baseline and at 1, 3, 5, and 10 years of follow-up. The efficacy of the Strengthening Spleen and Draining Dampness therapy was analyzed using repeated measures analysis of variance (ANOVA). Kaplan-Meier survival curves and multivariate proportional hazards model (Cox regression models) were employed to identify factors associated with treatment outcomes.

RESULTS: A total of 265 patients were included, with a median follow-up duration of 96 months (36, 122). TCM treatment significantly reduced 24-h urinary protein levels (P < 0.001), and increased serum albumin levels (P < 0.001), while serum creatinine remained stable (P = 0.187). Remission rates at 1, 3, 5, and 10 years were 52.81%, 69.71%, 68.39%, and 72.36%, respectively, and the rates of avoiding composite outcome events at the same intervals were 98.27%, 94.29%, 94.19%, and 93.50%. In the subgroup receiving TCM only, remission rates were 56.67%, 84.44%, 76.32%, and 82.86%. For patients treated initially with Western Medicine followed by TCM, the rates were 52.83%, 65.85%, 67.47% and 67.75%. In the cohort of patients who received TCM as their first-line therapy, remission rates were 49.23%, 62.50%, 61.76%, and 69.23%. Multivariate Cox regression analysis revealed that the duration of TCM treatment [hazard ratio (HR) = 0.826, 95% confidence interval (CI) (0.779, 0.876), P < 0.001], presence of hypertension [HR = 1.912, 95% CI (1.181, 3.094), P = 0.008], baseline serum albumin level [HR = 0.930, 95% CI (0.894, 0.969), P < 0.001], and the rate of serum albumin increase within the first year of treatment [HR = 0.930, 95% CI (0.909, 0.957), P < 0.001] were significantly associated with clinical outcomes.

CONCLUSION: The Strengthening Spleen and Draining Dampness therapy demonstrated robust short- and long-term efficacy in treating IMN, with high rates of remission and renal survival over 10 years. Key factors influencing clinical remission included the duration of TCM treatment, baseline serum albumin levels, the presence of hypertension, and the rate of increase in serum albumin within the first year. These findings suggest that this TCM approach provides a viable long-term treatment option for IMN.

Key words: glomerulonephritis, membranous, long-term renal survival, risk factors, efficacy evaluation, strengthening spleen and draining dampness

KE Tianxingjian, CHEN Wanjia, XIANG Ling, DENG Yueyi, WANG Yiquan, LIU Wangyi, XING Yue, LU Zhenzhen, GAO Hongzhi. Clinical evaluation of strengthening spleen and draining dampness in the treatment of idiopathic membranous nephropathy: a retrospective 10-year follow-up study[J]. Journal of Traditional Chinese Medicine, 2025, 45(4): 881-890.

Figures/Tables 9

References 40.

1.	Zhu P, Zhou FD, Wang SX, et al. Increasing frequency of idiopathic membranous nephropathy in primary glomerular disease: a 10-year renal biopsy study from a single Chinese nephrology centre. Nephrology (Carlton) 2015; 20: 560-6.
2.	Xu X, Wang G, Chen N, et al. Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol 2016; 27: 3739-46. PMID
3.	Köllner SMS, Seifert L, Zahner G, Tomas NM. Strategies towards antigen-specific treatments for membranous nephropathy. Front Immunol 2022; 13: 822508.
4.	Deng L, Xu G. Update on the application of monoclonal antibody therapy in primary membranous nephropathy. Drugs 2023; 83: 507-30. DOI PMID
5.	Wang X, Cui Z, Zhang YM, et al. Rituximab for non-responsive idiopathic membranous nephropathy in a Chinese cohort. Nephrol Dial Transplant 2018; 33: 1558-63.
6.	Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med 2019; 381: 36-46.
7.	Gauckler P, Shin JI, Alberici F, et al. Rituximab in membranous nephropathy. Kidney Int Rep 2021; 6: 881-93. DOI PMID
8.	Ronco P, Beck L, Debiec H, et al. Membranous nephropathy. Nat Rev Dis Primers 2021; 7: 69. DOI PMID
9.	van de Logt AE, Fresquet M, Wetzels JF, et al. The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney Int 2019; 96: 1292-302.
10.	Chen Y, Deng Y, Ni Z, et al. Efficacy and safety of Traditional Chinese Medicine (Shenqi particle) for patients with idiopathic membranous nephropathy: a multicenter randomized controlled clinical trial. Am J Kidney Dis 2013; 62: 1068-76. DOI PMID
11.	Wang YH, Sun LY, Li MM, Wang Y, Li XY, Liao X. Clinical evidence of oral Chinese patent medicines in treatment of chronic kidney disease: a scoping review. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2023; 29: 99-108.
12.	Liu CY, Hu JF. The using of warming kidney and dredging collaterals in patients with idiopathic membranous nephropathy, Guo Ji Zhong Yi Zhong Yao Za Zhi 2019; 41: 229-33.
13.	Fernández-Juárez G, Rojas-Rivera J, Logt AV, et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int 2021; 99: 986-98.
14.	Storrar J, McDonnell T, Ragy O, et al. Time for a relook? An update on primary membranous nephropathy incidence in a large UK cohort. Clin Kidney J 2024; 17: 1-2.
15.	Ramachandran R, Kumar V, Bharati J, et al. Long-term follow-up of cyclical cyclophosphamide and steroids versus tacrolimus and steroids in primary membranous nephropathy. Kidney Int Rep 2021; 6: 2653-60. DOI PMID
16.	Shi B, Zhang RR, Liang Y, et al. Efficacy of Traditional Chinese Medicine regimen Jianpi Qushi formula for refractory patients with idiopathic membranous nephropathy: a retrospective case-series study. Evid Based Complement Alternat Med 2018; 2018: 5854710.
17.	Shan W, Guan H, Gu H, et al. Traditional Chinese Medicine for idiopathic membranous nephropathy: a systematic review and Meta-analysis. Heliyon 2024; 10: 1-13.
18.	Chen X, Chen Y, Shi K, et al. Comparison of prognostic, clinical, and renal histopathological characteristics of overlapping idiopathic membranous nephropathy and IgA nephropathy versus idiopathic membranous nephropathy. Sci Rep 2017; 7: 11468. DOI PMID
19.	Radice A, Trezzi B, Maggiore U, et al. Clinical usefulness of autoantibodies to M-type phospholipase A2 receptor (PLA2R) for monitoring disease activity in idiopathic membranous nephropathy (IMN). Autoimmun Rev 2016; 15: 146-54. DOI PMID
20.	Ronco P, Debiec H. Pathophysiological advances in membranous nephropathy: time for a shift in patient's care. Lancet 2015; 385: 1983-92. DOI PMID
21.	Bally S, Debiec H, Ponard D, et al. Phospholipase A2 receptor-related membranous nephropathy and mannan-binding lectin deficiency. J Am Soc Nephrol 2016; 27: 3539-44. PMID
22.	du Buf-Vereijken PW, Branten AJ, Wetzels JF. Membranous nephropathy study group. cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate. Nephrol Dial Transplant 2004; 19: 1142-8.
23.	Jha V, Ganguli A, Saha TK, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am Soc Nephrol 2007; 18: 1899-904. DOI PMID
24.	Lin S, Li HY, Zhou T, et al. Efficacy and safety of cyclosporine A in the treatment of idiopathic membranous nephropathy in an Asian population. Drug Des Devel Ther 2019; 13: 2305-30.
25.	Yu X, Ruan L, Qu Z, et al. Low-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness and renal safety. Ren Fail 2017; 39: 688-97. DOI PMID
26.	Sato M, Takei T, Moriyama T, et al. Long-term outcomes of initial therapy for idiopathic membranous nephropathy. Clin Exp Nephrol 2017; 21: 842-51. DOI PMID
27.	Waldman M, Austin HA 3rd. Controversies in the treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 2009; 5: 469-79. DOI PMID
28.	Schieppati A, Perna A, Zamora J, et al. Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev 2004; (4): CD004293.
29.	Zhang XD, Cui Z, Zhang MF, et al. Clinical implications of pathological features of primary membranous nephropathy. BMC Nephrol 2018; 19: 215.
30.	Couser WG. Primary membranous nephropathy [published correction appears in Clin J Am Soc Nephrol. 2017 Sep 7; 12 (9):1528]. Clin J Am Soc Nephrol 2017; 12: 983-97.
31.	Kaneko K, Kimata T, Tsuji S, et al. Serum albumin level accurately reflects antioxidant potentials in idiopathic nephrotic syndrome. Clin Exp Nephrol 2012; 16: 411-4. DOI PMID
32.	Qiu Y, Qiu Y, Yao GM, et al. Natural product therapies in chronic kidney diseases: An update. Nephrol Ther 2022; 18: 75-9.
33.	Qiao L, Gao ZQ, Guo ZA, Jin Y. Mechanisms of active components of Astragalus membranaceus in regulating the NLRP3 inflammasome to attenuate diabetic nephropathy. Guo Ji Lao Nian Yi Xue Za Zhi 2025; 46: 360-4.
34.	Qin Q, Niu J, Wang Z, et al. Astragalus membranaceus inhibits inflammation via phospho-P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways in advanced glycation end product-stimulated macrophages. Int J Mol Sci 2012; 13: 8379-87. DOI PMID
35.	Cao Y, Ruan Y, Shen T, et al. Astragalus polysaccharide suppresses doxorubicin-induced cardiotoxicity by regulating the PI3k/Akt and p38MAPK pathways. Oxid Med Cell Longev 2014; 2014: 674219.
36.	Zhong Y, Deng Y, Chen Y, et al. Cijiang He J. Therapeutic use of traditional Chinese herbal medications for chronic kidney diseases. Kidney Int 2013; 84: 1108-18. DOI PMID
37.	Huang SH, Hu YF. Clinical effect of Wenyang Lishui decoction combined with Huangqi injection in the treatment of nephrotic syndrome patients. Yi Liao Zhuang Bei 2018; 31: 116-7.
38.	Wang BZ, Zhao YJ, Hou YY. The effect of Huangqi injection on blood lipids and hemorheology in nephrotic syndrome. Heilongjiang Zhong Yi Yao 2020; 49: 11.
39.	Nie RY, Xiong GL, Fu T, Pan MQ. Network Meta-analysis of Chinese medicine injections for the intervention of proteinuria in diabetic nephropathy. Guangzhou Zhong Yi Yao Da Xue Xue Bao 2025; 42: 518-30.
40.	Wen M, Küchle C, Sarkar O, et al. Plasmapheresis combined with rituximab for refractory idiopathic membranous nephropathy. Int Urol Nephrol 2014; 46: 847-8. DOI PMID

Item	Baseline	1 year (n = 231)	3 years (n = 175)	5 years (n = 155)	10 years (n = 123)
24-h urinary protein (g/d)	4.3±2.7	2.6±2.5^a	1.8±2.1^a	1.9±1.9^a	1.7±2.7^a
serum albumin (g/L)	25.6±6.8	30.3±9.8^a	34.6±9.1^a	35.4±8.4^a	37.0±8.7^a
Serum creatinine (μmol/L)	77.2±35.4	84.0±64.0	83.0±56.2	92.6±74.6	97.8±100.8
eGFR (EPI formula)	93.3±25.5	91.5±30.1	90.2±27.2	85.9±29.9	80.8±28.2^a

Item	Baseline	1 year (n = 231)	3 years (n = 175)	5 years (n = 155)	10 years (n = 123)
24-h urinary protein (g/d)	4.3±2.7	2.6±2.5^a	1.8±2.1^a	1.9±1.9^a	1.7±2.7^a
serum albumin (g/L)	25.6±6.8	30.3±9.8^a	34.6±9.1^a	35.4±8.4^a	37.0±8.7^a
Serum creatinine (μmol/L)	77.2±35.4	84.0±64.0	83.0±56.2	92.6±74.6	97.8±100.8
eGFR (EPI formula)	93.3±25.5	91.5±30.1	90.2±27.2	85.9±29.9	80.8±28.2^a

Group	Time	n	24-h urinary protein (g/d)	serum albumin (g/d)	Serum creatinine (μmol/L)	eGFR (EPI formula)
TCM1	0 year	66	4.3±2.2	26.3±6.5	67.3±19.2	100.1±18.4
	1 year	60	2.2±2.3	32.6±9.7	62.2±20.7	104.3±20.6
	3 years	45	1.2±1.9	38.7±7.8	66.9±26.4	99.3±18.8
	5 years	38	1.6±1.9	36.7±8.0	81.0±54.6	90.3±24.3
	10 years	35	1.1±2.2	39.4±6.2	73.4±27.7	83.8±17.5
TCM2	0 year	128	4.2±2.9	25.2±6.9	86.1±45.8	87.6±29.3
	1 year	106	2.8±2.0	29.4±9.3	97.6±86.1	85.9±33.1
	3 years	82	1.8±1.7	33.7±9.4	87.5±60.4	87.7±29.3
	5 years	83	1.9±2.0	35.1±8.4	90.3±63.6	86.0±29.6
	10 years	62	2.3±3.2	34.7±8.3	104.4±120.4	80.1±29.2
TCM & WM	0 year	71	4.5±2.5	25.7±6.8	70.2±16.9	97.2±21.7
	1 year	65	2.8±3.4	29.7±10.5	81.2±36.0	89.3±29.1
	3 years	48	2.1±2.6	32.5±8.9	90.5±66.7	85.8±28.9
	5 years	34	2.3±1.9	34.7±8.6	110.1±110.0	81.3±36.0
	10 years	26	1.0±1.5	39.8±10.7	105.9±96.7	79.6±34.7

Group	Time	n	24-h urinary protein (g/d)	serum albumin (g/d)	Serum creatinine (μmol/L)	eGFR (EPI formula)
TCM1	0 year	66	4.3±2.2	26.3±6.5	67.3±19.2	100.1±18.4
	1 year	60	2.2±2.3	32.6±9.7	62.2±20.7	104.3±20.6
	3 years	45	1.2±1.9	38.7±7.8	66.9±26.4	99.3±18.8
	5 years	38	1.6±1.9	36.7±8.0	81.0±54.6	90.3±24.3
	10 years	35	1.1±2.2	39.4±6.2	73.4±27.7	83.8±17.5
TCM2	0 year	128	4.2±2.9	25.2±6.9	86.1±45.8	87.6±29.3
	1 year	106	2.8±2.0	29.4±9.3	97.6±86.1	85.9±33.1
	3 years	82	1.8±1.7	33.7±9.4	87.5±60.4	87.7±29.3
	5 years	83	1.9±2.0	35.1±8.4	90.3±63.6	86.0±29.6
	10 years	62	2.3±3.2	34.7±8.3	104.4±120.4	80.1±29.2
TCM & WM	0 year	71	4.5±2.5	25.7±6.8	70.2±16.9	97.2±21.7
	1 year	65	2.8±3.4	29.7±10.5	81.2±36.0	89.3±29.1
	3 years	48	2.1±2.6	32.5±8.9	90.5±66.7	85.8±28.9
	5 years	34	2.3±1.9	34.7±8.6	110.1±110.0	81.3±36.0
	10 years	26	1.0±1.5	39.8±10.7	105.9±96.7	79.6±34.7

Item	1 year (n = 231)	3 years (n = 175)	5 years (n = 155)	10 years (n = 123)
CR	40 (17.32)	59 (33.71)	54 (33.55)	52 (42.28)
PR	82 (35.50)	63 (36.00)	52 (34.84)	37 (30.08)
Remission rate (%) (CR+PR)	122 (52.81)	122 (69.71)	106 (68.39)	89 (72.36)
RE	0 (0.00)	1 (2.50)	6 (10.16)	10 (18.52)

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