Immune-mediated membranous nephropathy: Long term fluconazole usage caused podocyte autophagy.

The primary consequences of membranous nephropathy (MN) are the development of nephrotic syndrome including hypogammaglobulinemia, the increased infectious risk, the loss of protein-bound vitamin D, and, above all, an elevated thromboembolic incidence of up to 50% in severe proteinuria patients. Membrane nephropathy may be either idiopathic or primary, not recognized (70%-80%) or secondary (20%-30%) to pathological sicknesses such as hepatitis B, systemic lupus erythematosus, malignancies, and side-effects of medicines. The immunological responses in MN involve multiple components: immunoglobulin G (IgG), long-escaped antigens, and the membrane attachment complex, formed by the supplement to form C5b-9. In general, IgG4 is the most significant IgG subclass deposited in idiopathic membranous nephropathic disease but fluctuating IgG1 levels also are linked with immunological deposits. In contrast, IgG1, IgG2, and IgG3 deposition are greater than IgG4 deposition in secondary nephropathy. Fluconazole is a synthetic antifungal triazole that is often used. It is well tolerated in general and has never been identified as a cause of nephropathies. We report on the development of MN caused by fluconazole therapy that could potentiate podocyte autophagy.

A Review of the Current Practice of Diagnosis and Treatment of Idiopathic Membranous Nephropathy in China.

Idiopathic membranous nephropathy (IMN), a common pathological type of nephrotic syndrome, is one of the main causes of kidney failure. With an increasing prevalence, IMN has received considerable attention in China. Based on recent studies, we discuss advances in the diagnosis of IMN and the understanding of its genetic background. Although the pathogenesis of IMN remains unclear, our understanding has been substantially enhanced by the discovery of new antigens such as phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A, exostosin1/exostosin2, neural epidermal growth factor-like 1 protein, neural cell adhesion molecule 1, semaphorin 3B, and factor H autoantibody. However, due to ethnic, environmental, economic, and lifestyle differences and other factors, a consensus has not yet been reached regarding IMN treatment. In view of the differences between Eastern and Western populations, in-depth clinical evaluations of biomarkers for IMN diagnosis are necessary. This review details the current treatment strategies for IMN in China, including renin-angiotensin system inhibitors, corticosteroid monotherapy, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil, adrenocorticotropic hormone, and traditional Chinese medicine, as well as biological preparations such as rituximab. In terms of management, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines do not fully consider the characteristics of the Chinese population. Therefore, this review aims to present the current status of IMN diagnosis and treatment in Chinese patients, and includes a discussion of new approaches and remaining clinical challenges.

[Meta-analysis of Yiqi Huoxue method in treating idiopathic membranous nephropathy].

The incidence of idiopathic membranous nephropathy (IMN) is increasing year by year, and the clinical research on Chinese medicine treatment of INM is also growing. This study aims to evaluate the efficiency and safety of Yiqi Huoxue method for IMN. Data sources used were from PubMed, EMbase, the Cochrane Library, CBM, CNKI, Wanfang and VIP database. Two researchers independently screened the literature and extracted data. RevMan 5.3 software was used for Meta analysis, and the evidences were graded for the outcomes according to GRADE system by using GRADEprofiler 3.6. Eventually, eleven trials (725 participants) were included in the Meta-analyses. There was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in 24 h UTP [RR=-1.23, 95%CI=(-1.94,-0.53), P=0.000 6] or when combining all trials in ALB [RR=3.56, 95%CI=(1.64, 5.47), P=0.000 3]. Meanwhile, there was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in TC [RR=-0.39, 95%CI=(-0.57, -0.20), P<0.000 1] or when combining all trials in TG [RR=-0.49, 95%CI=(-0.82, -0.15), P=0.004]. However, there was no statistically significant difference between Yiqi Huoxue method and controls when combining all trials in Scr [RR=-3.25, 95%CI=(-9.35, 2.84), P=0.30] or when combining all trials in BUN [RR=-0.81,95%CI=(-2.29, 0.66), P=0.28]. In the statistics, the most frequently used Chinese medicines in clinical application were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizome and Salvia Miltiorrhiza. The present evidences suggested that Yiqi Huoxue method should be thought highly of in the treatment of IMN, and at the same time, the rational use of traditional Chinese medicine, such as Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma also should be paid attention to. However, due to the GRADE evidence grading of the primary outcome measure of 24 h UTP had very low quality, this review can not provide high-quality evidence to prove the clinical efficacy of this method. More well-designed and large-scale multi-center randomized controlled trials should be conducted in the future for verification.

[Toxic nephropathy secondary to occupational exposure to metallic mercury]. / Nefropatía membranosa secundaria a exposición laboral con mercurio metálico.

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

[Indices of lipid metabolism in children with dysmetabolic nephropathy undergoing balneotherapy with nitric-silicon thermal water].

The authors show positive dynamics of lipid metabolism in children with dysmethabolic nephropathy under condition of use of Annensk mineral water at spa stage of medical rehabilitation. Quantity of "useful" high-density lipoproteins was increased; initially increased indices of low- and very low-density lipoproteins were decreased. Level of cholesterol, triglycerides and index of atherogenia were decreased too. All these factors makes possible to consider silicon thermal water as a correcting factor of lipid metabolism in children with dysmethabolic nephropathy.

Alternative therapies and future intervention for treatment of membranous nephropathy.

Despite a multitude of investigation over the last 2 decades, the treatment of membranous nephropathy remains both controversial and suboptimal. Recent progress in the molecular pathways of inflammation and immunologic regulation holds the promise of offering futuristic alternatives and/or supplements to the standard regimen of glucocorticoids and alkylating agents. Several potential points of intervention along the path of disease development and expression have been identified: modulation of the immune response to the pathogenetic antigen; inactivation of the inflammatory pathways responsible for B and T cell activation; blockade of pathogenetic antibody formation by B and T cells; blockade of the complement cascade; blockade of lipid peroxidation of glomerular basement membrane components; and blockade of renal fibrosis resulting from proteinuria, lipiduria, and/or inflammation. These points of intervention form the basis for our discussion of such varied potential therapies for membranous nephropathy as: vaccines, inhibitors of tissue plasminogen activator, humanized monoclonal antibodies, mycophenolate mofetil, pentoxifylline, and others.

A prospective clinical trial comparing the treatment of idiopathic membranous nephropathy and nephrotic syndrome with simvastatin and diet, versus diet alone.

Of 17 patients with idiopathic membranous nephropathy (IMN) and nephrotic syndrome, 9 were allocated to treatment with simvastatin (an HMG CoA-reductase inhibitor) and low cholesterol diet, and 8 to diet alone. At entry, the treatment and control groups did not differ in mean serum creatinines, chromium-labelled EDTA clearances, urinary protein/creatinine ratios, serum albumins, and lipid profiles. The mean follow up period (+/- SEM) in the treated group was 19.3 (+/- 4.4) months compared with 16.6 (+/- 5.9) months in the control group. At the end of the trial the fall in chromium-labelled EDTA clearances was similar (-1.27 versus -1.28 mls/min/months/1.73 m2) in the treatment and control groups respectively. The mean (+/- SEM) total and LDL-cholesterol had gone from 10.5 (+/- 0.94) and 8.02 (+/- 1) mmol/l to 5.2 (+/- 0.49) and 3.47 (+/- 0.44) respectively in the treated patients. Additionally the mean (+/- SEM) albumin and urinary protein/creatinine ratio went from 25.6 (+/- 2.4) gm/l and 0.52 (+/- 0.09) gm/mmol to 45.5 (+/- 2.8) and 0.13 (+/- 0.04) respectively. There was little change in total and LDL-cholesterol; albumin and urinary protein/creatinine ratio in the control group. This study supports the observation that lowering serum cholesterol in the nephrotic syndrome reduces proteinuria and increases serum albumin levels. No difference in the rate of decline in renal function could be demonstrated.