This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.
Humans ; Nonprescription Drugs/therapeutic use* ; Network Meta-Analysis ; Glomerulonephritis, Membranous/drug therapy* ; Bayes Theorem ; Capsules ; Delayed-Action Preparations ; Drugs, Chinese Herbal/adverse effects* ; Tablets

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in chronic glomerulonephritis(CGN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with CGN was retrieved from databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to March 2023. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 and RevMan 5.4.1 software were used to analyze the data of the literature that met the quality standards. Finally, 71 RCTs were included, involving 7 Chinese patent medicines. The total sample size was 6 880 cases, including 3 441 cases in the test group and 3 439 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenyanshu Capsules/Granules/Tablets+conventional western medicine, Huangkui Capsules+conventional western medicine, and Bailing Capsules+conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Huangkui Capsules+conventional wes-tern medicine, and Bailing Capsules+conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Bailing Capsules+conventional western medicine, and Shenyan Kangfu Tablets+conventional western medicine.(4) In terms of reducing 24hUTP, the top 3 optimal interventions according to SUCRA were Shenyan Kangfu Tablets+conventional western medicine, Bailing Capsules+conventional western medicine, and Huangkui Capsules+conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Bailing Capsules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Yishen Huashi Granules+conventional western medicine.(6) In terms of reducing BUN, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Bailing Capsules+conventional western medicine.(7) In terms of improving the clinical total effective rate, the top 3 optimal interventions according to SUCRA were Huangkui Capsules+conventional western medicine, Kunxian Capsules+conventional western medicine, and Yishen Huashi Granules+conventional western medicine. The results showed that the combination of conventional western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of conventional western medicine and Chinese patent medicine was superior to conventional western medicine alone in reducing Scr, BUN, and 24hUTP, and improving the clinical total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.
Humans ; Tumor Necrosis Factor-alpha ; Network Meta-Analysis ; Nonprescription Drugs ; C-Reactive Protein ; Interleukin-6 ; Drugs, Chinese Herbal/therapeutic use* ; Glomerulonephritis/drug therapy*

Objective: To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods: The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney U test and Fisher's exact probability test were used for comparison between the groups. Results: Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) vs. 7 (3, 12) years, Z=-2.52, P=0.011), a lower preceding infection rate (45% (9/20) vs. 11/13, P=0.032) and lower spontaneous remission rate (0 vs. 4/13, P=0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 vs. 5/15, P=0.031) and low albumin levels at renal biopsy ((25±6) vs. (29±7) g/L, t=2.14, P=0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all P>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) vs. 6.0 (2.5, 22.3) months, Z=-2.27, P=0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all P>0.05). Conclusion: Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.
Autoantibodies ; Child ; Complement C1q/metabolism* ; Female ; Glomerulonephritis, Membranous/drug therapy* ; Humans ; Immunoglobulin A/immunology* ; Immunoglobulin G ; Kidney Glomerulus ; Male ; Retrospective Studies

Animals ; Glomerulonephritis, IGA/drug therapy* ; Hydroxychloroquine/therapeutic use* ; Ki-67 Antigen ; Kidney ; Rats ; Toll-Like Receptor 4/genetics* ; Vitamin D

Objective To investigate the prognosis predictors of anti-neutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis treated with glucocorticoid(GC).Methods The clinicopathological data of patients with biopsy-confirmed ANCA-associated glomerulonephritis were retrospective analyzed by retrieving the medical database in Peking Union Medical College Hospital from January 2000 to May 2015. Pathological categories were re-classified. Renal remission rates,infection rates,and death events were compared between intravenous glucocorticoid(GC)pulse therapy group and non-pulse group. Logistic regression analysis was performed to analyze factors influencing the short-term prognosis.Results Among the 81 patients with ANCA-associated glomerulonephritis,49(60.5%)received GC pulse therapy and 32(39.5%)did not. The GC pulse group had significantly lower estimated glomerular filtration rate at baseline(eGFR0)than the non-pulse group(t=3.003,P=0.015)but significantly higher 24-hour urinary protein(24 hUP)(t=2.394,P=0.002)and Birmingham Systemic Vasculitis Activity Score(BVAS)(t=0.049,P=0.013). There was no significant difference in the cumulative amount of cyclophosphamide(CTX)(t=1.336,P=0.245)between these two groups. The overall renal remission rate of GC pulse group in the 6 month was significantly lower(48.7% vs. 79.3%;χ =6.591,P=0.024). Univariate analysis showed that baseline 24 hUP(t=6.222,P=0.017),eGFR0(t=3.727,P=0.046),and pathological category(χ =7.654,P=0.045)were associated with the overall renal remission rate in the 6 month. Multivariate analysis showed the crescent category was an independent factor(OR=20.63,95%CI:2.217-191.973,P=0.008;compared with sclerotic category)for overall renal remission rate in the 6 month,while GC pulse therapy was not an predictor(OR=0.271,95%CI:0.062-1.179,P=0.082). A total of 37 patients experienced infections within 6 months. The infection rate in GC pulse group(55.1%,27/49)was significantly higher than that of non-pulse group(31.3%,10/32)(P=0.042). Univariate regression analysis showed that eGFR0(t=1.912,P=0.049),baseline BVAS(t=-3.360,P=0.001)and GC pulse(χ =6.249,P=0.014)were associated with infection events within 6 months. Multivariate analysis showed that the baseline BVAS was the only predictor with 1.089 times for every 1 point increase in BVAS(OR=1.089,95%CI:1.006-1.179,P=0.034). Conclusions Crescentic category favors renal remission independently compared with sclerotic category. Patients with crescentic category may benefit more from intensive treatment. BVAS acts as an independent risk factor of infection.
Antibodies, Antineutrophil Cytoplasmic ; Glomerulonephritis ; drug therapy ; Glucocorticoids ; therapeutic use ; Humans ; Prognosis ; Retrospective Studies

OBJECTIVE: To study the clinical effect and safety of tacrolimus (TAC) combined with glucocorticoid (GC) versus mycophenolate mofetil (MMF) combined with GC in the treatment of primary IgA nephropathy (IgAN) in children. METHODS: A retrospective analysis was performed for the clinical data of children with primary IgAN confirmed by renal pathology between January 2012 and December 2017. These children were divided into TAC group and MMF group according to the treatment regimen. Their clinical data before treatment and at 1, 3, and 6 months of treatment were collected, and the remission status of IgAN and adverse reactions were compared between the two groups. RESULTS: A total of 43 children who met the inclusion criteria were enrolled, with 15 children in the TAC group and 28 children in the MMF group. At 1 month of treatment, there was no significant difference in the remission status between the two groups (P>0.05). At 3 and 6 months of treatment, the TAC group had a significantly better remission status than the MMF group (P<0.05). At 1 month of treatment, the TAC group had higher serum albumin levels than the MMF group (P<0.05). Both groups had a significant increase in serum albumin levels at each time point after treatment (P<0.0083) and a significant increase in the glomerular filtration rate (GFR) at 3 and 6 months of treatment (P<0.0083). There was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05), but fungal infection was observed in one child from the TAC group. CONCLUSIONS TAC combined with GC can effectively reduce urinary protein in children with primary IgAN, and it has a better short-term clinical effect than MMF combined with GC, with good safety.
Child ; Drug Therapy, Combination ; Glomerulonephritis, IGA ; drug therapy ; Glucocorticoids ; therapeutic use ; Humans ; Immunosuppressive Agents ; Mycophenolic Acid ; Retrospective Studies ; Tacrolimus ; therapeutic use

BACKGROUNDIn vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats.

METHODSBovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1β) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance.

RESULTSCompared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1β (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1β and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1β, and serum IL-1β were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPiogroup (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01).

CONCLUSIONSOur study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

Animals ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Glomerulonephritis, IGA ; drug therapy ; genetics ; metabolism ; Interleukin-1beta ; genetics ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Inbred Lew ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; drug effects ; genetics ; Thiazolidinediones ; therapeutic use ; Toll-Like Receptor 4 ; genetics ; metabolism

BACKGROUNDAccording to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN.

METHODSA total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test.

RESULTSOf the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN (P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3rd month.

CONCLUSIONSThere were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

Adult ; Autoantibodies ; metabolism ; Female ; Glomerulonephritis, Membranous ; drug therapy ; metabolism ; pathology ; urine ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Phospholipase A2 ; metabolism ; Retrospective Studies

Lupus-like glomerulonephritis is an immune complex disease with features of lupus nephritis in the absence of systemic lupus erythematosus (SLE). We report a 49-year-old man diagnosed with lupus-like glomerulonephritis associated with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). He was admitted to the hospital for edema. At admission, the serum creatinine was 2.2 mg/dL and the urine protein level was 3.9 mg/day. A renal biopsy showed features of lupus nephritis with no clinical or serological evidence of SLE. Extranodal marginal zone B-cell lymphoma of MALT was discovered concurrently. After successful chemotherapy, the lupus-like glomerulonephritis and lymphoma entered complete remission.
Biopsy ; Creatinine ; Drug Therapy ; Edema ; Glomerulonephritis* ; Humans ; Immune Complex Diseases ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Middle Aged

Granulomatosis with polyangiitis (GPA) is an idiopathic vasculitis of medium and small arteries, characterized by necrotizing granulomatous inflammation. GPA typically affects upper and lower respiratory tract with coexisting glomerulonephritis. This disease is generally characterized by antineutrophil cytoplasm antibodies (ANCA), nevertheless, there are rare cases with negative ANCA. GPA affects people at any age, with predominance of the sixth and seventh decade of life. In 80%-95% of the patients the first symptoms of GPA are otorhinolaryngological manifestations of head and neck including nose/sinuses, ears, eyes, larynx/trachea, oral cavity, and salivary glands. Diagnosis of GPA is based on Criteria of the American College of Rheumatology. In clinical practice diagnosis, the presence of distinctive ANCA antibodies and biopsy of affected organ are crucial. GPA must be differentiated from neoplastic, infectious or inflammatory ulcerative lesions of the head and neck. The standard treatment procedure is divided into two essential phases, induction and maintenance. The induction phase is based on combination of systemic corticosteroid and immunosuppressant therapy, whereas the maintenance phase comprises corticosteroids and azathioprine/methotrexate supplementation. Surgical treatment ought to be considered for patients who are not responding to pharmacotherapy.
Adrenal Cortex Hormones ; Antibodies ; Antibodies, Antineutrophil Cytoplasmic ; Arteries ; Biopsy ; Cytoplasm ; Diagnosis ; Drug Therapy ; Ear ; Glomerulonephritis ; Head ; Humans ; Inflammation ; Mouth ; Neck ; Otolaryngology ; Respiratory System ; Rheumatology ; Salivary Glands ; Ulcer ; Vasculitis ; Wegener Granulomatosis