Network Meta-analysis of Chinese patent medicines in treatment of idiopathic membranous nephropathy / 中国中药杂志

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.

Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report / Glomeruloesclerose Segmentar e Focal e Nefropatia Membranosa sobrepostas em paciente com Síndrome Nefrótica: relato de caso

Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.

Therapy of tacrolimus combined with corticosteroids in idiopathic membranous nephropathy

We evaluated the efficacy and safety of tacrolimus (TAC) combined with corticosteroids in treating patients with idiopathic membranous nephropathy (IMN). One hundred seventy-seven biopsy-proven IMN patients were recruited in this retrospective clinical study. Sixty patients received TAC (target blood concentration of 4–8 ng/mL) and 117 patients received daily cyclophosphamide (CYC, 100 mg) combined with prednisone. Remission rates at the end of the first, second and third month in the TAC group were significantly higher than that in the CYC group (1st: 35.0 vs 19.7%, P<0.05; 2nd: 56.7 vs 38.5%, P<0.05; 3rd: 76.7 vs 59.0%, P<0.05). In the first 3 months, daily urinary protein and serum albumin in the TAC group obtained a better improvement than that in the CYC group (P<0.05). At the end of the sixth and the twelfth month, the remission rates, daily urinary protein and serum albumin were all comparable between the two groups (P>0.05). No significant difference of relapse rate between the groups was found (16.3 vs 12.0%, P>0.05). Patients were more likely to develop glucose intolerance in the TAC group. The TAC regimen obtained more benefits in treating IMN patients, especially in the first 3 months, than the CYC regimen.

Stepwise Treatment Using Corticosteroids Alone and in Combination with Cyclosporine in Korean Patients with Idiopathic Membranous Nephropathy

PURPOSE: We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome. MATERIALS AND METHODS: The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months. RESULTS: There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01). CONCLUSION: Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

No abstract available.

Experience of Anti-Viral Therapy in Hepatitis B-Associated Membranous Nephropathy, Including Lamivudine-Resistant Strains

BACKGROUND/AIMS: Chronic hepatitis B infection is a common cause of secondary membranous nephropathy (MN) in endemic areas. Lamivudine treatment improves renal outcome in patients with hepatitis B virus-associated MN (HBV-MN), but prolonged use leads to the emergence of lamivudine-resistant variants. We describe our experience treating lamivudine-resistant and other strains of HBV-MN with new antiviral drugs. METHODS: Of the 89 patients biopsied and diagnosed with MN from 1996 to 2011, 10 positive for hepatitis B surface antigen were recruited for this study. We investigated the clinical courses, therapeutic responses, and prognoses of patients with HBV-MN. RESULTS: The incidence of HBV-MN among the original 89 patients was 11.2%. Of these patients, four were treated with supportive care and six with antiviral drugs. One of the four patients treated with supportive care had a spontaneous remission. Four of the six patients treated with antiviral drugs were given lamivudine, and the other two were given entecavir. Two of the four patients treated with lamivudine achieved complete remission with seroconversion (i.e., development of anti-hepatitis B e antigen antibodies), whereas the other two had lamivudine-resistant strains, which were detected at 22 and 23 months after lamivudine treatment, respectively. We added adefovir to the treatment regimen for one of these patients, and for the other patient we substituted clevudine for lamivudine. Both of these patients experienced complete remission, as did the two patients initially treated with entecavir, neither of whom showed resistance to the drug. CONCLUSIONS: New nucleoside analogues, such as entecavir, adefovir, and clevudine, can be effective for treatment of HBV-MN, including lamivudine-resistant strains.

Curso clínico de la nefropatía membranosa lúpica pura / Long-Term outcome of type V lupus membranous glomerulonephritis

Background: The long-term outcome of the pure form of WHO type V lupus membranous glomerulonephritis is apparently more benign than that of other forms of lupus glomerulonephritis. However 12percent of such patients progress to terminal renal failure. The presence of proteinuria may be an indication of cytotoxic agents. Aim: To study the clinical long-term outcome of WHO type V lupus membranous glomerulonephritis. Material and methods: A retrospective analysis of all kidney biopsies of a University Pathology Department, with the diagnosis of WHO type V lupus membranous glomerulonephritis. Review of medical records of patients with the disease and one clinical assessment of all living patients. Results: Between 1973 and 2000, 703 kidney biopsies were done to patients with systemic lupus erythematosus. Of these, 40 were membranous glomerulonephritis and in 33 patients (28 women, age range 6-71 years), data on the evolution and survival was obtained. Nineteen had type Va and the rest type Vb nephritis. Two presented with renal failure and 11 with proteinuria over 3.5 g/24h. The median follow-up since the renal biopsy was 63 months (range 1-316). At the end of follow-up, four had a creatinine clearance of less then 15 ml/h and four a clearance between 15 and 29 ml/h (one of these received a renal allograft). Eleven (33percent) patients had died, mostly due to infections. Life expectancy at five years with a creatinine clearance over 15 ml/h was 75percent. Bad prognostic factors were an elevated creatinine clearance over 15 ml/h was 75percent. Bad prognostic factors were an elevated creatinine and high blood pressure at the moment of the biopsy. Conclusions: The clinical outcome of these patients was bad. Twelve percent reached a stage of terminal renal failure. This is in contrast with the 3percent progression to a similar stage of proliferative glomerulonephritis treated with i.v. cyclophosphamide. New therapies for this condition must be sought.

La nefropatia membranosa del adulto / Membranous kidney diseases in adults

La glomerulopatía membranosa es el fenotipo histológico más frecuentemente asociado al síndrome nefrótico en el adulto y si bien globalmente la sobrevida renal a 10 años es del 70%, su evolución en el paciente individual depende de la función renal en el momento del diagnóstico, la naturaleza y extensión del daño glomerular y túbulo-intersticial, la presencia de hipertensión y la magnitud de la proteinuria. Si bien sehan desarrollado modelos matemáticos para predecir su historia natural, la capacidad para predecirla es limitaday excepto en mujeres jóvenes con función renal normal, una biopsia renal con poca esclerosis, normotensióny proteinuria no nefrótica, en general el tratamiento medicamentoso se ve apoyado por los resultados obtenidosen estudios controlados y aleatorizados. El uso de esteroides con clorambucil o ciclofosfamida, o laciclosporina A son los recursos terapéuticos de valor mejor establecido para inducir remisiones duraderas de laproteinuria y preservación de la función renal, si bien el micofenolato mofetil y tal vez el rituximab se incorporen al uso habitual en especial en casos resistentes a las dos alternativas anteriores.

Membranous Glomerulopathy as a Manifestation of Chronic Graft-versus-Host-Disease After Non-myeloablative Stem Cell Transplantation in a Patient with Paroxysmal Nocturnal Hemoglobinuria

Allogeneic stem cell transplantation (allo-SCT) using related or unrelated donor could eradicate paroxysmal nocturnal hemoglobinuria (PNH) clones and may cure the disease. Chronic graft-versus host disease (GVHD) is a major complication of patients who have undergone allo-SCT. Nephrotic syndrome has been described as one of the rare manifestations of chronic GVHD following the usual myeloablative allo-SCT. We report a case of nephrotic syndrome that developed 25 months after non-myeloablative allo-SCT for PNH. The patient had grade II acute GVHD and extensive chronic GVHD after non-myeloablative allo-SCT. Typically the patient presented with preserved renal function and full nephrotic syndrome including generalized edema, proteinuria, hypoalbuminemia, and hypercholesterolemia. Renal biopsy revealed findings of membranous glomerulopathy (MG). The patient is alive with a stable engraftment and full donor chimerism under the administration of tacrolimus for control of chronic GVHD and MG without refractory hemolysis and cytopenia.

Survival analysis of Thai patients with IgM nephropathy, focal segmental glomerulosclerosis and membranous nephrotic syndrome.

Long term outcome of 124 Thai adult nephrotic patients was determined. Nephrotic syndrome affects the young more often than the old (median age 29 years). The most common pathology was IgM nephropathy (45.2%), membranous nephropathy (31.5%) and FSGS (23.4%). Sixty-four per cent of patients with IgM nephropathy respond to corticosteroid within 4-8 weeks while twenty three per cent were late responders. However, more than half of these patients were relapsers or steroid dependent. Response to corticosteroid occurred in 48.2 per cent of patients with FSGS while the response rate of patients with membranous nephropathy was only 23.1 per cent. Survival analysis revealed that five and ten years renal survival of IgM nephropathy was 98 per cent. Five and ten years renal survival of FSGS was 83.7 per cent and 76.8 per cent while those of membranous nephropathy was 95 per cent and 63.3 per cent. The response to corticosteroid was associated with better prognosis in FSGS. Our results show that patients with IgM nephropathy and membranous nephropathy have a generally good prognosis. Renal function is usually well preserved for at least ten years. The prognosis of patients with FSGS varied and correlated with the degree of steroid responsiveness.

Alpha-Interferon therapy for HBV-related glomerulonephritis

We report a case of a patient with hepatitis B virus (HBV)-related membranous glomerulonephritis (MGN) who showed improvement after interferon-alpha (IFN-alpha) therapy. A 35-year-old man with nephrotic syndrome and HBV antigens received a 24-week course of IFN-alpha. At the end of therapy there was an elevation in the level of plasma aminotransferase and an increase in proteinuria, which were followed by antigen/antibody seroconversion. This "flare-up" before seroconversion suggests an increase in disease activity in the liver and kidney, demonstrating in vivo HBV involvement in MGN.

Effect of long-term treatment with insulin and/or acarbose on glomerular basement membrane thickening in alloxan-diabetic rats

Acarbose is a competitive inhibitor of the intestinal alpha-glycosidases, that can delay absorption of intestinal carbohydrates causing their malabsorption. In the present paper we studied the effects of insulin, acarbose and their association on glomerular basement membrane thickening in alloxan-diabetic rats. Twenty-five male and female Wistar rats, approximately 3 months old at the beginning of the experiment, were assigned randomly to each of five experimental groups: normal control rats, alloxan-diabetic control rats, alloxan-diabetic rats treated with acarbose, alloxan-diabetic rats treated with insulin, and aloxan-diabetic rats treated with insulin plus acarbose. Alloxan was administered in a single iv dose of 42 mg/kg body weight. Insulin was given subcutaneously at doses of 18 to 30 IU/kg corrected daily on the basis of glycosuria and ketonuria. Acarbose was given mixed with rat chow in a dose of 50 mg/100 g chow. Body weight, water and food intake and diuresis, as well as blood and urine glucose were determined after 1, 3, 6, 9, and 12 months of treatment. Glomerular basement membrane (GBM) thickening was determined by electron microscopy at the same times. Clear clinical and laboratory signs of severe diabetes, with blood glucose levels above 200 mg/dl and urine glucose above 3000 mg/dl, were observed in all alloxan-diabetic control rats, in all periods of follow-up, whereas administration of insulin or acarbose reduced the blood glucose levels of treated groups. The most satisfactory control of blood and urine glucose was observed in animals treated with both insulin and acarbose. However, diarrhea was observed in diabetic rats treated with acarbose associated or not with insulin, GBM thickening was correlated with age in all groups. Beginning at six months after diabetes induction, the GBM of untreated diabetic rats was significantly thicker (mean + 4.446 + 0.45 mm) than that of normal rats (2.977 + 0.63 mm). Both insulin and acarbose prevented GBM thickening and their combination induced thickening similar to the age-dependent thickening observed for normal rats of the same age. We conclude that acarbose when combined with insulin may be a good option in the control of diabetes and its renal complications.

Prognosis and management of membraneous nephropathy.

Patients of idiopathic membranous nephropathy (MGN) were randomly assigned to received steroid and cyclophosphamide every other month (Gr-I) and steroid alone (Gr-II). Of 36 patients in Gr.I, 33 patients achieved complete remissions, 2 had relapsing course with remission on further courses of therapy and only one has reached end stage renal failure. In contrast, of the 35 patients in Gr. II, 15 (P < 0.001) achieved complete remission, 7 are in partial remission, 5 have no response, another 5 have deterioration of renal function of which two required dialysis, and 3 have relapsing course after the initial remission. Mean follow up period was 46 +/- 10.2 months. We conclude that steroid and cyclophosphamide every other month is highly effective in achieving remission in patients with membranous nephropathy.

Effect of captopril on heavy proteinuria in patients with various glomerular diseases

The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p< 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p< 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven.

Síndrome nefrótica por glomerulonefrite membranosa associada a leucemia mielóide crônica / Nephrotic syndrome due to membranous glomerulonephritis associated with chronic myeloid leukemia

Os autores relatam caso de um paciente que apresentou síndrome nefrótica quatro anos após o diagnóstico de leucemia mielóide crônica. A biópsia renal revelou lesöes características da glomerulopatia membranosa. Acreditamos que este represente o primeiro caso relatado na literatura da associaçäo entre leucemia mielóide crônica e glomerulopatia membranosa