Primary membranous nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. Rituximab monotherapy has emerged as a front-line treatment for patients with PMN, but potential markers for predicting the response to rituximab are unknown.
In this single-arm retrospective pilot study, 48 patients with PMN without previous immunosuppressive therapy were enrolled. All patients were treated with rituximab and were followed up for at least 6 months. The primary end point was the achievement of complete or partial remission at 6 months. The subsets of lymphocytes were collected at baseline, 1 month, 3 months and 6 months to identify prognostic factors for achieving remission of PMN with rituximab therapy.
A total of 58.3% of patients (28/48) achieved remission. Lower serum creatinine, greater serum albumin, and greater phospholipase A2 receptor antigen detected in kidney biopsy at baseline were found in the remission group. After multiple adjustments, a high percentage of natural killer (NK) cells at baseline, especially ≥15.7%, was strongly associated with remission (relative risk = 1.62; 95% CI, 1.00-2.62; P = 0.049), and patients with a response to rituximab had a greater mean percentage of NK cells during the follow-up period compared with nonresponders. Analysis using a receiver operating characteristic curve indicated prognostic value of the NK-cell percentage at baseline, with an area under the curve of 0.716 (95% CI, 0.556-0.876; P = 0.021).
The findings from this retrospective pilot study suggest that a high percentage, especially ≥15.7%, of NK cells at baseline might predict a response to rituximab treatment. These findings provide a basis for designing larger-scale studies to test the predictive value of NK cells in patients with PMN undergoing rituximab treatment.

BACKGROUND: Several statistical models for predicting prognosis of primary membranous nephropathy (PMN) have been proposed, most of which have not been as widely accepted in clinical practice.
METHODS: A systematic search was performed in MEDLINE and EMBASE. English studies that developed any prediction models including two or more than two predictive variables were eligible for inclusion. The study population was limited to adult patients with pathologically confirmed PMN. The outcomes in eligible studies should be events relevant to prognosis of PMN, either disease progression or response profile after treatments. The risk of bias was assessed according to the PROBAST.
RESULTS: In all, eight studies with 1237 patients were included. The pooled AUC value of the seven studies with renal function deterioration and/or ESRD as the predicted outcomes was 0.88 (95% CI: 0.85 to 0.90; I2 = 77%, p = 0.006). The paired forest plots for sensitivity and specificity with corresponding 95% CIs for each of these seven studies indicated the combined sensitivity and specificity were 0.76 (95% CI: 0.64 to 0.85) and 0.84 (95% CI: 0.80 to 0.88), respectively. All seven studies included in the meta-analysis were assessed as high risk of bias according to the PROBAST tool.
CONCLUSIONS: The reported discrimination ability of included models was good; however, the insufficient calibration assessment and lack of validation studies precluded drawing a definitive conclusion on the performance of these prediction models. High-grade evidence from well-designed studies is needed in this field.

Primary membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in the adult population. Although the discovery of different autoantibodies against glomerular/podocytic antigens have highlighted the role of B cells in the pathogenesis of MN, suboptimal response or even resistance to B cell-directed therapies occurs, suggesting that other pathophysiological mechanisms are involved in mediating podocyte injury. The complement system plays an important role in the innate immune response to infection, and dysregulation of the complement system has been observed in various kidney diseases. There is compelling evidence of complement cascade activation in primary MN, with the mannose-binding lectin (MBL) and alternative pathways particularly implicated. With appropriate validation, assays of complements and associated activation products could hold promise as adjunctive tools for non-invasive disease monitoring and prognostication. While there is growing interest to target the complement system in MN, there is concern regarding the risk of infection due to encapsulated organisms and high treatment costs, highlighting the need for clinical trials to identify patients most likely to benefit from complement-directed therapies.

Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA). We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed. We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached. In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.

Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.