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.

Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients.

The current research aimed to investigate the correlation between the effect of Wuzhi soft capsule (WZC) on FK506 concentration and CYP3A5 gene polymorphism in patients with membranous nephropathy (MN).Seventy-five patients with idiopathic MN were enrolled and divided according to the expression of CYP3A5 gene metabolic enzyme into group A (CP3A5 metabolic enzyme function expression types CYP3A5*1/*1 type and CYP3A5*1/*3 type), and group B (non-expression type CYP3A5*3/*3 type). All patients were given oral administration of tacrolimus capsule at the initial dose of 1 mg for twice a day 1 hour before breakfast and dinner. Afterwards, the oral administration of WZC was added at the dose of 0.5 g for 3 times a day within half an hour after 3 meals.The blood concentrations of FK506 in groups A and B were significantly higher than those before administration. Compared with that before administration, the FK506 blood concentration was increased by 3.051 ±â€Š0.774 ng/ml after adding the WZC. Besides, the blood concentrations of FK506 in group A were lower than those in group B before and after administration; meanwhile, the 24 hours total urine protein and the biochemical indexes in both groups displayed no statistically significant difference. Only 1 case of diarrhea was observed, which was relieved after the reduction of tacrolimus.Wuzhi soft capsule can significantly increase the blood concentration of FK506 in MN patients. Moreover, the CYP3A5 genotyping should be considered when WZC is used to increase the blood concentration of FK506.

Sanqi oral solution ameliorates renal damage and restores podocyte injury in experimental membranous nephropathy via suppression of NFκB.

Membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults. However, the current treatment of MN has been a matter of fierce debate for decades, and the needs for more advanced pharmaceuticals are critical for improving the treatment strategies. Sanqi oral solution (SQ), mainly consisting of Radix Astragali and Radix Notoginseng, is a formulated product to treat chronic kidney disease for over 20 years with good efficiency in clinic, while the role of SQ on MN remains unclear. In this study, by establishing an experimental rat model of membranous nephropathy induced by cationic Bovine Serum Albumin (C-BSA), we tried to investigate the effects of SQ. We found that administration of SQ ameliorated MN by reducing proteinuria, elevating serum albumin, and ameliorating pathological renal damages. SQ also significantly reduced the C3 and IgG depositions, and restored podocin and synaptopodin expressions. Furthermore, SQ inhibited the activation of nuclear factor-kappa B (NF-κB) signaling pathway. Our results provide evidence that SQ exerts a novel therapeutic effect on MN via reducing proteinuria, ameliorating renal damage and restoring podocyte injuries, which are associated with the suppression of NFκB.

Characteristics of patients diagnosed with renal vein thrombosis and glomerulopathy: a case series.

BACKGROUND: Few contemporary studies have evaluated the clinical characteristics of patients with biopsy-proven glomerulopathy diagnosed with renal vein thrombosis (RVT). METHODS: Retrospective case series study within an integrated health system in a 12-year period (January 1, 2000 through December 31, 2011) investigating clinical characteristics of all adult patients who underwent native or transplant kidney biopsy and also had a diagnosis of RVT. Patient characteristics, diagnostic studies, and outcomes were evaluated. RESULTS: Among 3763 eligible patients, 17 had imaging confirmed RVT. Of these, 15 had membranous nephropathy (idiopathic or secondary to autoimmune disease). Although the biopsy population included primary and secondary glomerular disease patients, all 17 RVT patients had severe nephrotic syndrome and profound hypoalbuminemia with mean (SD) of albumin: 1.5 g/dL (0.66). CONCLUSION: Clinically significant RVT in patients with glomerulopathy appears to be a rather rare entity, occurring predominantly in patients with severe nephrotic syndrome due to idiopathic membranous nephropathy and membranous nephropathy secondary to autoimmune disease.

Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent.

Overview of current and alternative therapies for idiopathic membranous nephropathy.

Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, which is characterized by edema, hypoalbuminemia, hyperlipidemia, lipiduria, and proteinuria. Determination of idiopathic membranous nephropathy (IMN) disease progression risk is important for guiding initial therapy, with immunosuppressive therapy being reserved for high-risk patients. Because IMN may spontaneously remit in approximately 30% of patients, it is important to carefully select which patients should begin immunosuppressive therapy so as to maximize clinical benefit while limiting toxicity. An observation period of at least 6 months with conservative management that includes the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers is recommended. Initial treatment in high-risk IMN is a 6-month course of alternating steroids and alkylating agents. Calcineurin inhibitors (CNIs) represent an alternative first-line therapeutic option for high-risk patients who refuse treatment with steroid or alkylating agent therapy or for whom these treatments are contraindicated. Additional options are essential for patients with IMN who fail to adequately respond to initial therapies or who cannot use recommended therapies due to contraindications or intolerance, risks associated with repetitive dosing with alkylating agents, or potential exacerbation of impaired renal function with CNIs. While evidence for the use of alternative therapies in IMN is modest at best, our review summarizes the available literature for rituximab, mycophenolate mofetil, adrenocorticotropic hormone, intravenous immunoglobulin, and azathioprine. Rituximab has generally demonstrated beneficial outcomes with limited toxicity. Evidence supports a role for mycophenolate mofetil, although the evidence is of low quality and limited duration. Results from ongoing studies are required before adrenocorticotropic hormone can be recommended as therapy for treatment-resistant patients. Intravenous immunoglobulin and azathioprine are unlikely to have a role in IMN. With the advent of new tools and biomarkers measuring disease activity combined with new data regarding possible treatment options, the management and prognosis of IMN are likely to improve.

[Clinical observation of Shen No. 9 Recipe with Qingre Moshen Granule on the treatment of idiopathic membranous nephropathy after treated by multiple Western drugs with no efficacy].

OBJECTIVE: To observe the clinical efficacy of Shen No. 9 Recipe (SR) combined with Qingre Moshen Granule (QMG) in treatment of idiopathic membranous nephropathy (IMN) patients with no efficacy after treated by hormone or immunosuppressive agent, and further to explore the possible mechanism of this method in treatment of IMN by detecting the cellular immune function and cytokine interleukin-2 (IL-2). METHODS: Forty-four IMN patients with no efficacy after treated by multiple Western drugs were recruited from October 2007 to October 2009. They took SR (one dosage daily, oral administration in two portions) and QMG (each package each time, thrice daily) for 24 weeks. The 24-h urine protein, glomerular filtration rate (GFR), plasma albumin (Alb), serum creatinine (SCr), urea nitrogen (BUN), triglyceride (TG), serum total cholesterol (TC), levels of cellular immune function (CD4+, CD8+, CD4+/CD8+ ratio), and IL-2 were detected before and after treatment. The changes of Chinese medicine syndrome and adverse reactions were observed and recorded. RESULTS: After treatment the complete remission rate, the basic remission rate, and the total effective rate was 4.5%, 68.2%, 84.1%, respectively. The total markedly-effective rate of Chinese medicine syndrome was 90.9%. The Chinese medicine syndrome was significantly lower than before treatment (P < 0.01). The 24-h urine protein obviously decreased (P < 0.01), Alb obviously increased (P < 0.01), levels of TC and TG obviously decreased (P < 0.01, P < 0.05). There was no obvious change in levels of SCr and BUN (P > 0.05). The GFR significantly increased (P < 0.05). CD4+ and the ratio of CD4+/CD8+ were obviously elevated (P < 0.01) and the CD8+ obviously decreased (P < 0.01). The expression level of IL-2 obviously increased, but it still was lower than the normal value, showing statistical difference (P < 0.01). CONCLUSIONS: SR + QMG showed definite efficacy in treatment of IMN patients with no efficacy after treated by multiple Western drugs. It could improve the level of cellular immunity and improve abnormal expression levels of IL-2.

[Mechanical research on effects of yishenqing on membranous nephropathy].

OBJECTIVE: To investigate the therapeutic effect and mechanism of Yishenqing on rabbit membranous nephropathy. METHOD: The rabbit membranous nephropathy model was induced by cationic bovine serum albumin, and the immunity of mice together with urine volume and haemorheological property of rats were also estimated. RESULT: Yishenqing could significantly reduce the urinary protein content, preserve the renal function and pathologically restore the glomeruli. Moreover, its effects also include immunity enhancement, diuretic property and blood stasis amelioration. CONCLUSION: Yishenqing has good effects on the rabbit membranous nephropathy, which is probably due to the effects of diuretic property, immunity enhancement and blood stasis amelioration.

Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition.

The effect of mycophenolate mofetil (MMF) was examined in active Heymann nephritis (HN), an animal model of human membranous nephropathy. HN was induced in Lewis rats with Fx1A/complete Freund's adjuvant (CFA), and controls only received CFA. The induction of HN was prevented by MMF (30 mg/kg per d) from 0 to 4 wk after immunization. Proteinuria was not different in CFA controls up to 16 wk, and was significantly less than in untreated HN from 6 wk onward. Serum anti-Fx1A antibody (Ab) levels and glomerular Ig deposition were suppressed during therapy. The interstitial infiltrate of alphabetaTCR+, CD4+ and CD8+ T cells, natural killer cells, and macrophages (mphi) observed in untreated HN at 8 wk was absent from rats treated from 0 to 4 wk with MMF. Semiquantitative reverse transcription-PCR for renal mononuclear cell cytokine mRNA at 8 wk demonstrated that MMF from 0 to 4 wk prevented the increased expression of Th1 (interferon-gamma, lymphotoxin), Th2 (interleukin-4), and mphi (tumor necrosis factor-alpha) cytokines identified in untreated HN. In lymph node draining sites of immunization, MMF limited both enlargement and the increased proportion of CD3+, CD4+, and CD8+ T cells observed in untreated HN and CFA controls. MMF suppressed Th2 (interleukin-4) but not Th1 (interferon-gamma, lymphotoxin) cytokine mRNA expression in lymph nodes. MMF from 4 to 8, 6 to 12, or 10 to 14 wk did not prevent proteinuria, serum anti-Fx1A Ab, or glomerular IgG deposition when compared with untreated HN. This study showed that MMF from 0 to 4 wk prevented the induction of HN and was associated with preferential suppression of Th2 cytokines. This therapy may prove useful in human idiopathic membranous nephropathy.