Primary membranous nephropathy in two siblings with one combined with anti-glomerular basement membrane disease: a case report.

BACKGROUND: The phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear. CASE PRESENTATION: We describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01. CONCLUSION: We describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

The characters of antibodies against PLA2R in healthy individuals and in the patient with PLA2R associated membranous nephropathy.

BACKGROUND: Most primary membranous nephropathy (MN) is mediated by anti-phospholipase A2 receptor (PLA2R) antibodies. Recently, these antibodies have been revealed months to years before the disease's onset. Their production and pathogenicity need further investigation. METHODS: Anti-PLA2R antibodies were purified from plasma of eight healthy individuals, 12 patients with PLA2R-related MN and negative circulating antibody (Ab-), and 18 patients with positive anti-PLA2R antibodies (Ab +), using affinity column coupled with recombinant human PLA2R. The antigen specificity, antibody amount, titer, IgG subclass, and affinity were assessed by Western blot, immunofluorescence, ELISA, and surface plasmon resonance. RESULTS: The natural anti-PLA2R antibodies recognized the conformational structure of PLA2R which locates on the cell membrane of podocytes. The amount of natural IgG was 0.12 ± 0.04 g/L, which accounted for 0.80% of total IgG and was lower than that of patients (2.36%, P < 0.001). The titer of natural antibodies was lower than that of patients in Ab- and Ab + groups (1:16 vs. 1:43 vs. 1:274, P < 0.001). IgG2(45.1%) was predominant in natural antibodies, while IgG4 was predominant in Ab + group (45.7 vs. 25.0%, P < 0.001). IgG1 was increasing from natural antibodies to Ab- and Ab + groups. The affinity of natural antibodies was lower than that of patients (KD: 641.0 vs. 269.0 vs. 99.6 nM, P = 0.002). The antibody titer, affinity, and IgG4 percentage were associated with the severity of proteinuria and the stages of membranous lesion. CONCLUSIONS: The natural anti-PLA2R antibodies exist in healthy plasma. The antibody titer, IgG subclass, and affinity may participate in the pathogenesis of anti-PLA2R antibodies.

Effects of hydroxychloroquine on proteinuria in membranous nephropathy.

BACKGROUND: Many patients with primary membranous nephropathy have severe proteinuria unresponsive to optimized renin-angiotensin-aldosterone system inhibitors (RAASi). We evaluated the efficacy and safety of hydroxychloroquine as an adjunctive agent in membranous nephropathy (MN) treatments. METHODS: We prospectively recruited 126 patients with biopsy-proven primary membranous nephropathy and urinary protein 1-8 g/day while receiving optimized RAASi treatment for ≥ 3 months and well-controlled blood pressure. Forty-three patients received hydroxychloroquine and RAASi (hydroxychloroquine-RAASi group), and 83 patients received RAASi alone (RAASi group). Treatment responses, including proteinuria reduction, complete and partial remission rates, and autoantibody against phospholipase A2 receptor (anti-PLA2R) levels, were compared between the two groups at 6 months and over the long term. RESULTS: At 6 months, the effective response rate (proteinuria reduction > 30%) (57.5% vs. 28.9%, P = 0.002), clinical remission rate (35.0% vs. 15.7%, P = 0.015), and percentage change in proteinuria (- 51.7% vs. - 21.9%, P < 0.001) were higher, and the rate of switching to immunosuppressants (25.0% vs. 45.8%, P = 0.027) was lower in the hydroxychloroquine-RAASi group than in the RAASi group. Hydroxychloroquine administration was an independent protective factor with an effective response (OR 0.37, P = 0.021). In the long term, the clinical remission rate was higher in the HCQ-RAASi group (62.5% vs. 38.6%, P = 0.013). Hydroxychloroquine therapy was associated with a higher rate of anti-PLA2R reduction (< 20 U/ml) (HR 0.28, P = 0.031). We observed no serious adverse events associated with hydroxychloroquine. CONCLUSIONS: Hydroxychloroquine could be an option for patients with membranous nephropathy seeking to achieve proteinuria reduction and anti-PLA2R antibody reduction in addition to optimized RAASi. Randomized controlled trials are needed to confirm these findings. TRIAL REGISTRATION: ChiCTR2100045947, 20210430, retrospectively registered.

Effect of Intradialytic Exercise on Physical Performance and Cardiovascular Risk Factors in Patients Receiving Maintenance Hemodialysis: A Pilot and Feasibility Study.

INTRODUCTION: Although intradialytic exercise is considered a form of "nonpharmacological medicine" for patients receiving maintenance hemodialysis (MHD), this practice has not been widely implemented in most dialysis centers because of clinical limitations. We, therefore, aimed to design an intradialytic exercise training program to improve the implementation of this practice and determine its impact on physical performance and cardiovascular risk factors in patients receiving MHD. METHODS: A total of 132 MHD patients at 4 outpatient dialysis units were enrolled and assigned randomly into exercise (n = 67) and control groups (n = 65). During a 2-year period, patients in the exercise group participated in 20-min exercise training sessions within dialysis sessions on 3 days per week. All patients underwent assessments of physical function (6-min walk test) and cardiovascular risk factors (blood pressure [BP], total cholesterol [TC], low-density lipoprotein [LDL], high-sensitivity C-reactive protein [hsCRP], albumin [Alb], hemoglobin [Hb], and erythropoietin [EPO] dose) at the baseline and annually thereafter. RESULTS: Of the participants, 50.8% had completed the study after 2 years. No statistically significant intragroup or intergroup differences were observed in the measures of 6MD, BP, TC, hsCRP, Alb, Hb, and EPO dose. CONCLUSION: The results suggest that although this low-intensity, nonprogressive intradialytic exercise program may be practical, it was not sufficient to improve physiological function and reduce cardiovascular disease risk factors in patients receiving MHD.