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 study of altered calcium sensing system caused primary membranous nephropathy to end-stage renal failure.

PMN (primary membranous nephropathy) is the most prevalent source of idiopathic nephrotic syndrome, which further progressed to ESRD (end-stage renal disease) in non-diabetic adults worldwide. Autoantibodies circulating against podocyte membrane proteins PLA2R1 and THSD7A are present in approximately 75-80% of incidents. Furthermore, a research presented an unusual case of IgG4-RD correlated with elevated serum levels of calcium concluded that renal irregularities have been preceded and triggered by hypercalcemia. In-addition, previous research also indicates an elevated amount of calcium in the blood of PMN patients. However, we also found conflicting evidence from previous studies showing that autoantibodies that suppress the calcium-sensing receptor (CaSR) induce a high level of calcium in some cases of IgG4RD. Notably, the calcium ion plays a critical function not only as intracellular signaling molecule but binds extracellular receptor activity to intracellular events. Moreover, the raise in intracellular calcium levels during PMN is known as a crucial event involved in the activation of numerous nucleases, proteases and implicitly facilitates the release of prostaglandins, cytokines and superoxide radicals capable of causing cell damage and death. Thus, the precise mechanism of the PMN disease to renal failure is not fully clear and the disease incidence differs among patients. Therefore, we are hypothesizing the role of disrupted calcium signaling in PMN that progress to ESRD.

Rituximab for the management of idiopathic membranous nephropathy: a meta-analysis.

PURPOSE: The aim of this study was to evaluate the efficacy of rituximab therapy in the management of idiopathic membranous nephropathy (IMN). METHODS: After literature search, data from eligible studies were used to perform random-effects meta-analyses to estimate remission rates and changes in proteinuria at the latest follow-up after rituximab therapy. The outcomes were used for metaregression to identify the factors affecting the efficacy of rituximab. RESULTS: Twenty-one studies were included in the analysis (602 patients; age 50 years [95% CI 46.8, 53.3]; 30% females [95% CI 23, 31]). Follow-up duration was 20.3 months [95% CI 17.1, 23.5]. Remission rate (67% [95% CI 61, 73]) was higher in studies with below average baseline proteinuria (76% [95% CI 61, 88]) than in studies with above average baseline proteinuria (61% [95% CI 54, 68]). The complete and partial remission rates were 26% [95% CI 20, 33] and 37% [95% CI 31, 43], respectively. Rituximab therapy significantly reduced proteinuria (mean difference between final and baseline values: - 4.90 g/day [95% CI - 6.18, - 3.63]; p < 0.00001; % reduction: 62% [95% CI 57, 68]). The reduction in proteinuria was inversely associated with baseline serum albumin levels (p = 0.021) and the estimated glomerular filtration rate (p < 0.00001) and was positively associated with baseline proteinuria (p < 0.00001). The remission rate or decrease in proteinuria was not significantly related to the anti-PLA2R antibody status or previous immunosuppressant therapy. CONCLUSION: Rituximab therapy in IMN patients can provide approximately 67% remission rate. The reduction in proteinuria was greater in patients who had higher baseline proteinuria.