PMN is a major cause of nephrotic syndrome, particularly in adults. This disease is actually an immune-complex deposition disease that leads to thickening of the glomerular basement membrane and is associated with proteinuria, which further progresses to chronic kidney disease [1]. Therefore, there is a need for in-depth understanding of the pathogenesis of PMN when making more targeted treatment for better outcomes of patients [2,3].

Recent advances in the understanding of PMN have defined the role of autoantibodies against the M-type phospholipase A2 receptor (PLA2R) on podocytes [4]. Serum anti-PLA2R antibodies have been found as a specific marker for PMN, and their levels related to activity and severity of the disease. These results have particular implications for diagnosis, prognosis, and management in PMN [5]. Clinical presentation in PMN varies from simple asymptomatic proteinuria to nephrotic syndrome, while a minority progresses to end-stage renal disease. The level of proteinuria, renal function at presentation, and the ability for response to therapy determine the clinical presentation [6,7].

However, emerging evidence is showing that the serum levels of anti-PLA2R antibodies could actually serve as a predictor of clinical outcomes in patients with PMN. Anti-PLA2R levels are currently performed with the prime intention of learning about the effect on the clinical outcome of patients diagnosed with PMN [8,9]. The relationship of these antibody levels with a set of clinical parameters will be understood in detail to have better insight into the disease prognosis and guide therapeutic decision-making. In this regard, results from this study may, therefore, be very instrumental in risk stratification of the patients and individualization of treatment strategies in a bid to improve the management of PMN [10,11].

Study Design: This was a two-year hospital-based observational study to evaluate the predictive role of serum anti-PLA2R antibody level in the clinical outcome of primary membranous nephropathy patients. The study was approved by the institutional ethics committee of S.C.B. Medical College and Hospital, Cuttack, Odisha.

Study Area: This study was conducted in the Department of Nephrology and Renal Transplantation at S.C.B. Medical College and Hospital, Cuttack, Odisha.

Study Population: This study comprises all patients newly diagnosed with anti-PLA2R-associated PMN nephrotic syndrome from May 2021 to May 2023 at the identified hospital.

Inclusion Criteria:

• Patients with membranous nephropathy confirmed by renal biopsy and associated with the presence of anti-PLA2R antibodies.

Exclusion Criteria:

• Patients who had been lost to follow-up in the first half-year following diagnosis.
• Patients with secondary membranous nephropathy.
• Patients who did not consent in writing.

Data collection:

Baseline data were recorded at diagnosis, and follow-up data were collected each month during the course of the study. Clinical evaluation, demographic details, history of present illness, physical examination, and details of laboratory findings were noted on a structured proforma. All baseline laboratory investigations, including serum anti-PLA2R antibody level, were reassessed at six months.

Definitions: Nephrotic syndrome was defined as the presence of edema and serum albumin below 3.0 g/dL and 24-hour proteinuria greater than or equal to 3.5 g per 1.73 m² body surface area, with or without dyslipidemia. Complete clinical remission was considered when proteinuria decreased to 0.3 g/24 hours or less and serum albumin levels exceeded 3.5 g/dL. Partial remission was defined as proteinuria ranging between 0.3 and 3.5 g/day with a reduction of more than 50% from baseline levels.

Laboratory Parameters

The laboratory evaluations included:

• Complete Hemogram: Hemoglobin, total leukocyte count, mean corpuscular volume, platelet count.
• Liver Function Test: Serum aminotransferases (ALT and AST), serum bilirubin (total/direct), total protein/albumin, alkaline phosphatase.
• Lipid Profile: Triglycerides, total cholesterol, high-density and low-density lipoproteins.
• Electrolytes: Serum sodium, potassium, calcium.
• Urine Analysis: Routine and microscopy examination, protein creatinine ratio.
• Renal Function Test: Serum urea and creatinine.
• Immunological Tests: HIV, HBV, HCV, ANA, PSA.
• Renal Biopsy Report
• Imaging: Abdomen-pelvis ultrasonography; Chest X-ray.

The levels of serum anti-PLA2R antibodies were estimated in the MRU lab, S.C.B. Medical College and Hospital by ELISA. eGFR was calculated according to the CKD-EPI equation.

Statistical Analysis: The data analysis was done with SPSS software, version 17.0 for Windows. In the comparison of continuous variables with normal distribution, an independent sample t-test was used, while when variables had not undergone normal distribution, a Mann–Whitney U test was applied. Chi-square or Fisher's exact test was performed for categorical variables. Anti-PLA2R antibody level was stratified as either low. Comparison of the baseline and post-treatment data was done by appropriate statistical tests, where p<0.05 was taken to be significant.

Ethical Considerations: This research work was guided by the Declaration of Helsinki. This study had approval from the institutional ethics committee. Written informed consent was obtained from all participants, ensuring their confidentiality and privacy with regards to data collected for the study. Participants were free to withdraw from the research study at any point in time without prejudice.

 Table 1: Baseline Characteristics

This table provides an overview of the baseline characteristics of the study population, including age, serum creatinine, serum albumin, 24-hour urine protein, estimated glomerular filtration rate (eGFR), and Anti-PLA2R antibody levels. The parameters are presented as mean ± standard deviation, along with their respective ranges.

Key Findings on Anti-PLA2R Antibody Levels

Spontaneous Remission: The relationship between Anti-PLA2R antibody levels and spontaneous remission is depicted in the following table and graph.

Table 2: Anti-PLA2R Antibody Levels and Spontaneous Remission

This table outlines the relationship between Anti-PLA2R antibody levels and spontaneous remission in patients. It categorizes the patients based on low (<50 RU/ml) and high (>50 RU/ml) Anti-PLA2R antibody levels, indicating the number of patients achieving spontaneous remission versus those who did not, along with the percentage achieving spontaneous remission.

Graph 1: Anti-PLA2R Antibody Levels vs. Spontaneous Remission

This bar graph visually represents the percentage of patients achieving spontaneous remission at different Anti-PLA2R antibody levels, comparing the outcomes for patients with low and high antibody levels.

Remission with Immunosuppression: The table and graph below outline the impact of Anti-PLA2R antibody levels on remission with immunosuppressive therapy

Table 3: Anti-PLA2R Antibody Levels and Remission with Immunosuppression

This table demonstrates the effect of Anti-PLA2R antibody levels on remission in patients receiving immunosuppressive therapy. It divides patients into groups based on low and high antibody levels and shows the remission rates in each group, highlighting the percentage of patients achieving remission under immunosuppression.

Graph 2: Anti-PLA2R Antibody Levels vs. Remission with Immunosuppression

This bar graph illustrates the percentage of patients achieving remission under immunosuppressive therapy across different Anti-PLA2R antibody levels, contrasting the outcomes for patients with low and high antibody levels.

In this regard, we aimed to investigate the role of serum Anti-Phospholipase A2 Receptor Antibodies in predicting the outcome of primary MN. Our findings give a few useful details on the relation of PLA2R antibody levels with the clinical remission and treatment outcomes, which is an important parameter for the management of this condition[12][13].

The age distribution of patients in our study shows that primary MN mainly affects the middle-aged population, where most of the cases occurred between the age of 40-59 years [14]. It agrees with literature that membranous nephropathy is not seen primarily in the young but begins in the adult life period. Importantly, this gender distribution found the prevalence of MN higher in males, with a male-to-fale ratio of approximately 2.27:1. This supports earlier findings of male predominance in MN [15].

Baseline parameters of clinical findings A comparative analysis of the baseline parameters revealed different levels of renal impairment among patients enrolled. Creatinine values at entry into the study showed that nearly 40.8% of the patients had a value below 1 mg/dl, thereby suggesting relatively well-preserved renal function at least in some[16][17]. However serum creatinine levels were elevated in a significant percentage of the patients, depicting the varied disease manifestation of MN in the form of renal impairment. Similarly, the distribution of serum albumin levels showed that more than half of the patients have levels between 1-3 g/dl, reflecting the presence of significant nephrotic syndrome in this cohort [18].

Assessment of 24-hour urine protein showed that nearly 47% of the patients were having proteinuria falling in 4-7.9 g/dl, which can connote nephrotic range proteinuria by itself. A high quantum of proteinuria indicates very severe nephrotic syndrome in our study population [19][20]. This means that the distribution of eGFR value showed a marked difference in kidney function, in some showing nearly normal eGFR while, for others, the levels were substantially low [21].

One of the most significant among the findings in this discovery was the relation of Anti-PLA2R antibody titers to spontaneous remission. Our results indicate that patients with low levels of Anti-PLA2R antibodies (<50 RU/ml) would be related to this given biomarker to spontaneous remission in higher frequency compared with those possessing high levels [22][23].

All in all, 80% of the patients with a low responder status attained remission, while only 33% were high responders. This suggests that even low levels of Anti-PLA2R antibodies may be associated with a high likelihood of spontaneous remission in such patients with a conservative approach [24].

To add, the relationship between the level of Anti-PLA2R antibodies and remission under immunosuppressive therapy illustrates the predictive value of the antibodies. Patients with low levels of Anti-PLA2R antibodies under treatment with immunosuppressive had a much higher rate of remission at 83.3% than patients with high antibody levels, at 27.3%. This points to the potential utility of Anti-PLA2R antibody levels in guiding treatment decisions and predicting treatment responses in MN [25].

In summary, our study underlines the importance of Anti-PLA2R antibodies as a predictive marker for the outcome of primary membranous nephropathy. The level of the associated antibodies and the course of clinical remission are guided with and without the background of immunosuppressive therapy, offering special clinical value for making therapeutic decisions in the setting of this disease. The results will permit a more personalized approach to treatment of patients with MN. Future studies should continue to unveil the role of Anti-PLA2R antibodies in MN, hence their likely potential in guiding therapeutic approaches.

This work implicates serum Anti-PLA2R antibodies as possibly playing a role in primary MN prognosis. In this study, Anti-PLA2R antibody levels have an independent and strong association with the spontaneous remission that occurs with conservative management and after immunosuppressive therapy. Therefore, this will provide an association that Anti-PLA2R antibody level can give good value to act as a biomarker for deciding therapy and predicting the clinical response in MN. Results suggested that Anti-PLA2R antibody level measurements could help in making a prognosis of MN to have a more tailored approach in its management. Those patients who have high antibody levels may benefit from more aggressive treatment strategies, while those who have lower levels could achieve remission with more conservative measures. This study reiterates that Anti-PLA2R antibody testing ought to be used in clinical practice for betterment of treatment outcomes and optimization of patient care in primary membranous nephropathy.

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