|Year : 2021 | Volume
| Issue : 1 | Page : 3
Treatment of membranoproliferative glomerulonephritis with traditional chinese medicine and rituximab: A case report
Yao-wei Wang1, Qin Zeng2, Ren-huan Yu1
1 Department of Nephrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
2 Department of Nephrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences; Department of clinical medicine, Graduate School of Beijing University of Chinese Medicine, Beijing, China
|Date of Submission||01-Feb-2021|
|Date of Decision||31-Mar-2021|
|Date of Acceptance||08-Jul-2021|
|Date of Web Publication||08-Sep-2021|
Dr. Ren-huan Yu
Department of Nephrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Xiyuan Cao Chang, Haidian, Beijing 100091
Source of Support: None, Conflict of Interest: None
Membranoproliferative glomerulonephritis (MPGN) is usually characterized by refractory nephrotic syndrome and is associated with a poor prognosis. An older patient diagnosed with MPGN had a 20-year history of proteinuria and had clinical manifestations of nephrotic syndrome in the past 2 years. MPGN. Before the patients received an 11-month traditional Chinese medicine (TCM) treatment, the patient was treated with prednisone, tacrolimus, mycophenolate mofetil, and rituximab for 11 months. After 22 months, the urine protein level decreased to <1 g/d, with normal plasma albumin level, and remarkably increased glomerular filtration rate. Combination of TCM with Western medicine for 22 months was effective for the treatment of MPGN.
Keywords: Case report, membranoproliferative glomerulonephritis, rituximab, traditional Chinese medicine
|How to cite this article:|
Wang Yw, Zeng Q, Yu Rh. Treatment of membranoproliferative glomerulonephritis with traditional chinese medicine and rituximab: A case report. Integr Med Nephrol Androl 2021;8:3
|How to cite this URL:|
Wang Yw, Zeng Q, Yu Rh. Treatment of membranoproliferative glomerulonephritis with traditional chinese medicine and rituximab: A case report. Integr Med Nephrol Androl [serial online] 2021 [cited 2022 Aug 16];8:3. Available from: https://journal-imna.com//text.asp?2021/8/1/3/325660
| Introduction|| |
Membranoproliferative glomerulonephritis (MPGN) is characterized by deposition of immunoglobulin (Ig) and/or complements in the glomerulus, leading to mesangial capillary proliferation, capillary wall remodeling, double-contour formation, and glomerular lobulation. The main clinical manifestation of MPGN is nephrotic syndrome, often accompanied by persistent hypocomplementemia. At present, the treatment options for MPGN are limited, and the curative effect is not good. In addition, the prognosis is poor. Herein, we present a case of MPGN treated with integrated Chinese and Western medicine for 22 months, with a good effect.
Written informed consent for the publication of case details was obtained from the patient.
| Case Report|| |
The patient was a 65-year-old man. His physical examination results from 1999 showed that urine protein level was +. In 2015, his blood pressure was elevated, urine protein level was ++, and 24-h urine total protein (24 hUTP) was 2.8 g. A renal puncture was performed after the patient was admitted to the hospital. Light microscopy with periodic acid–Schiff staining showed glomerular diffusion, moderate-to-severe mesangial cell proliferation and mesangial matrix widening, endothelial cell segmental proliferation, poor opening of some capillary loops, parietal epithelial cell segmental proliferation and segmental wall thickening, and layering of Bowman's capsule. Renal tubules were multifocal and moderately atrophied, with visible protein casts; there was epithelial cell granular degeneration, interstitial multifocal and moderate fibrosis, and focal and mild inflammatory cell infiltration. The intima of the intrarenal artery was thickened to a greater extent than the media, with arteriolar hyaline. Periodic acid–silver methenamine and Masson staining showed a smaller number of granular eosinophils deposited under the endothelium and epithelium, as well as a thickened basement membrane, with the double-contour formation and no spikes. Immunofluorescence results were as follows: Granular deposition of IgG (+), complement C3 (++), and C1q (+) along the capillary loop; No IgA, IgM, complement C4, and fibrosis were detected. Electron microscopy was not performed at that time. MPGN was diagnosed, and the patient was treated with antihypertensive drugs. On regular follow-up examinations after discharge, his serum creatinine (Scr) was 69 μmol/L–92 μmol/L, and 24 hUTP was 1–2 g.
In August 2018, the patient developed severe edema of both lower limbs. His 24 hUTP was 17 g, urine red blood cell count was 10/high-power field, plasma albumin (ALB) was 29 g/L, Scr was 74 μmol/L, C3 was 61.7 mg/dL, and C4 was 9.6 mg/dL. He was negative for anti-phospholipase A2 receptor antibodies (<2 ru/mL), cryoglobulin, anti-neutrophil cytoplasmic antibodies, antinuclear antibodies, and hepatitis B and C antigen antibodies; immunofixation electrophoresis showed no abnormalities. A renal biopsy was performed again. For kidney pathology reports, 12 glomeruli were observed under light microscopy imaging study. Among them, one was with global sclerosis, two were with balloon adhesions, and one had cellular fibrous crescent glomerular diffusion, severe mesangial cell proliferation and mesangial matrix widening, diffusion and moderate proliferation of endothelial cells, neutrophil infiltration visible in the capillary lumen (with no microthrombosis), poor opening of the capillary loops, segmental proliferation of parietal epithelial cells, and segmental thickening of Bowman's cyst walls [Figure 1]. Immunofluorescence results were as follows: Granular deposition of IgG (+), IgM (+), C3 (++), C4 (+), and C1q (++) along the capillary loop; IgA (−); fibrosis (−); IgG1 (−); and IgG4 (−). Ig light chain κ (+) was deposited in a granular form along the capillary loop, while Ig light chain λ was negative [Figure 2]. Electron microscopy showed that glomerular mesangial cells and the stroma were heavily proliferated and widely inserted; endothelial cells were diffusely proliferated; there was a large amount of electron-dense deposits under the endothelium and a small amount in the mesangial area, with visible coarse granular structures inside, double-contour formations in the basement membrane, and extensive fusion of epithelial foot processes. Renal tubules showed increased numbers of lysosomes, renal interstitial lymphatic mononuclear cell infiltration, and collagen fiber proliferation [Figure 3]. The patient was treated with tacrolimus combined with prednisone acetate (15 mg/day). After 1.5 months, Scr rose to 143 μmol/L, and 24 hUTP was 9 g, indicating abnormalities of renal function; therefore, tacrolimus treatment was stopped.
|Figure 1: Light microscopy images of the second kidney biopsy specimen. (a) Glomerular diffusion, severe mesangial cell proliferation, and mesangial matrix widening, with visible neutrophil infiltration in the capillary lumen, are observed (PAS, ×200) (b) Interstitial inflammatory cell infiltration is observed (PAS, ×200) (c) Basement membrane thickening and numerous double-contour formations are observed (PASM, ×200). (d) Renal tubules are slightly atrophied, and some protein casts are observed in the upper-tube lumen (PASM, ×200). PASM, periodic acid&S#8211;silver metheramine; PAS, periodic acid–Schiff|
Click here to view
|Figure 2: Immunopathological imaging of the second kidney biopsy specimen IgG (+), IgM (+), C3 (2+), C4 (+), C1q (2+), and Ig light chain κ (+) are deposited as particles along the capillary loop (immunofluorescence, ×100)|
Click here to view
|Figure 3: Electron microscopy images of the second kidney biopsy specimen. (a) Glomerular mesangial cells and the stroma are heavily proliferated and widely inserted. Endothelial cells are diffusely proliferated, electron-dense deposits are observed in the subendothelial and mesangial areas, and coarse granular structures are observed within them (×5000). (b) Increased numbers of tubule lysosomes and renal interstitial lymphatic mononuclear cell infiltration, with collagen fiber hyperplasia, are observed (×8000)|
Click here to view
In October 2018, oral prednisone acetate (30 mg/d), combined with mycophenolate mofetil (1.5 g/d), was started. After more than 6 months of treatment, the condition of the patient did not improve, and his edema was aggravated with ascites. ALB was 15.3 g/L to 25 g/L, and 24 hUTP was 4.5 g to 11.5 g during this period. In May 2019, mycophenolate mofetil was stopped, and prednisone (15 mg/d) was combined with rituximab (500 mg), which was administered intravenously once a month for a total of two times.
The patient sought traditional Chinese medicine (TCM) treatment on July 15, 2019. By then, his 24 hUTP was 7.46 g, ALB was 26 g/L, and Scr was 154 μmol/L. He showed following symptoms: Severe edema of the whole body, fatigue and weakness, abdominal distension, a bitter and dry mouth, poor appetite, peaceful sleep, little urination, difficulty in bowel movement, a pale-red tongue, white greasy hair, and a thin and wiry pulse. The TCM syndrome differentiation was spleen deficiency and water stagnation, combined with dampness and heat in the middle jiao. The therapeutic principles were to invigorate the spleen, harmonize the stomach, and promote diuresis. The TCM formula included 40 g Sheng Huang qi (raw Astragalus membranaceus), 10 g Renshen (Radix panacis ginseng), 20 g Shengbaizhu (raw Rhizoma atractylodis macrocephalae), 30 g Fuling (Sclerotium Poria cocos), 10 g Chenpi (Pericarpium citri Reticulatae), 15 g Zisuye (Folium perillae frutescentis), 10 g Muxiang (Radix aucklandiae lappae), 10 g Binglang (Semen arecae catechu), 15 g Danggui (Radix angelicae sinensis), 15 g Chishao (Radix rubrus paeoniae lactiflorae), 30 g Danshen (Radix salviae miltiorrhizae), 20 g Guangfangji (Radix aristolochiae fangchi), 6 g Huanglian (Rhizoma coptidis chinensis), 10 g Zhigancao (honey-fried Radix Glycyrrhizae), 15 g Zhu ling (Sclerotium Polypori umbellati), and 5 slices of Shengjiang (Zingiber officinale Roscoe). This formula was decocted in water, one dose a day, and 100 mL was administered twice daily. This treatment was supplemented with a food therapy prescription (Huangqi Carp Decoction, twice a week). The ALB infusion was stopped, and hormones were gradually withdrawn. The blood pressure-lowering drugs, lipid-lowering drugs, low-molecular-weight heparin, diuretics, and other Western medicines remained unchanged.
At a follow-up visit on July 30, 2019, his appetite improved, and lower-limb edema was reduced. He still had fatigue, abdominal distension, a sticky stool, difficult bowel movements, a pale-red tongue, thin and wiry pulse, and a weight loss of 1 kg. The prescription was continued with modifications according to the symptoms. On October 22, 2019, his ALB was 28.6 g/L, and Scr dropped to 114 μmol/L. He had a good appetite, improved physical strength, significantly reduced edema, a dry and bitter mouth at night, abdominal distension, and a daily urine output of 1600 mL–1,900 mL. On December 19, 2019, his 24 hUTP was 3.96 g, and the previous prescription was continued with modifications. On January 19, 2020, his ALB increased to 33.1 g/L, Scr was 110 μmol/L, and 24 hUTP decreased to 1.78 g. The edema basically subsided, with no discomfort, and his urine volume was 1000–1500 mL. The previous prescription was continued with modifications, and the dosages of antihypertensive drugs were gradually reduced.
In June 2020, his 24 hUTP dropped to 0.85 g, Scr was 117 μmol/L, and ALB rose to 42.2 g/L. The quantitative changes in Scr, ALB, and urine protein are shown in [Figure 4] and [Figure 5].
| Discussion|| |
Western medicine treatment analysis
The patient was an older male with a 20-year history of proteinuria. At the beginning of his illness, he developed asymptomatic proteinuria, which later progressed to nephrotic syndrome and renal insufficiency. Two renal biopsies that were performed at different times both led to the diagnosis of MPGN, with Ig and complement depositions. Secondary factors were ruled out, and therefore, the diagnosis was idiopathic MPGN. Hormones, combined with tacrolimus, mycophenolate mofetil, or rituximab, and other treatments were adopted successively, as his condition gradually worsened. In this case, rituximab was used twice before the beginning of TCM treatment. Although the Scr level increased later, it cannot be ruled out that the curative effect was due to rituximab. In recent years, it has been reported that partial remission was achieved after using rituximab to treat MPGN.,,
Traditional Chinese medicine treatment analysis
First, TCM was used to relieve the patient's main symptoms of discomfort. At the initial TCM visit, the patient had a poor appetite, nausea, abdominal distension, and obvious physical fatigue. The TCM syndrome differentiation indicated spleen deficiency and damp-heat syndrome. Thus, the treatment method focused on invigorating the spleen, replenishing qi, harmonizing the stomach, and resolving turbidity. The prescription emphasized acrid opening and bitter down-bearing drugs. Renshen, Sheng Huang qi, Shengbaizhu, Fuling, and Zhigancao were used to invigorate the spleen and nourish qi; Huanglian, Zisuye, and Shengjiang were used as acrid opening and bitter down-bearing drugs to harmonize the stomach and resolve turbidity; Danggui, Chishao, and Danshen were used to activate the blood and remove stasis; Guangfangji was used to eliminate wind and dredge channels; and Zhuling, Binglang, and Chenpi were used to promote qi circulation and diuresis. Therefore, the whole prescription provides a combined effect to invigorate the spleen and nourish qi, harmonize the stomach, resolve turbidity, and promote blood circulation and diuresis.
After the digestive tract symptoms were relieved, the treatment focused on invigorating the spleen and kidney simultaneously, while promoting blood circulation and diuresis. After more than 2 months of TCM treatment, the patient subjectively felt that his symptoms disappeared. After 11 months, his urine protein fell below 1 g, ALB returned to normal, and the glomerular filtration rate significantly increased.
| Conclusion|| |
In this study, a patient with MPGN, who is mostly with a refractory nephrotic syndrome with very difficult clinical treatment and a poor prognosis, achieved good treatment results after 22 months of integrated Chinese and Western medicine therapy.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
We would like to thank the Pathology Lab of the PLA General Hospital for providing the kidney pathology report used in this article.
Financial support and sponsorship
Conflicts of interest
Ren-huan Yu is the Executive Editor-in-Chief of the journal. The article was subject to the journal's standard procedures, with peer review handled independently of this editor and his research groups.
| References|| |
Sugiura H, Takei T, Itabashi M, Tsukada M, Moriyama T, Kojima C, et al.
Effect of single-dose rituximab on primary glomerular diseases. Nephron Clin Pract 2011;117:c98-105.
Rudnicki M. Rituximab for treatment of membranoproliferative glomerulonephritis and C3 glomerulopathies. Biomed Res Int 2017;2017:2180508.
Lu Q, Zuo L, Dong B, Yan Y, Yang B. Rituximab treatment for immune-complex-mediated membranoproliferative glomerulonephritis. Immunotherapy 2018;10:1027-31.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]