Serum and urine biomarkers expression (PLA2R-Ag, anti-THSD7A Ab and RBP) in determining alternative methods of differentiating primary and secondary membranous glomerulonephritis

Introduction: Differentiating primary from secondary membranous glomerulonephritis (MGN) using biomarkers is an important consideration in establishing its diagnosis and treatment strategies. Biomarkers are also important in prognosticating MGN cases to end-stage renal disease (ESRD). A biopsy is an invasive procedure. It cannot prove morphologically secondary MGNs whatever more than morphology can precede identification of its underlying cause. A biopsy is also not able to prognosticate MGN cases to ESRD. Objectives: This study aimed at providing an alternative method in differentiating primary and secondary MGN using serum and urine biomarkers (PLA2R antigen (Ag) and anti-THSD7A antibodies (Ab)). It also aimed to demonstrate the importance of urine RBP as an effective biomarker for prognostication of MGNs to ESRD. Materials & Method: 125 patients were diagnosed with membranous glomerulonephritis (81 primary and 44 secondary MGN) from January 2012 to October 2019 in Hospital Serdang and Hospital Kuala Lumpur. Of this 125, only 69 were available and consented. Blood and urine samples were obtained for biomarkers analysis using enzyme-linked immunosorbent assay (ELISA) technique. Results: The proportion of primary and secondary MGN is 64.7% and 35.3% respectively. Both serum and urine PLA2R-Ag are detected in seven primary MGN patients and one secondary MGN, having a strong positive correlation between serum and urine PLA2R-Ag (R= 0.932, p < 0.05). There is a fair correlation of UPCr index with both serum (R= 0.502, p < 0.001) and urine (R= 0.437, p < 0.001) PLA2RAg. Serum anti-THSD7A Ab was found positive in one primary MGN subject and four secondary MGN subjects. In contrast, none of the subjects shows any anti- THSD7A Ab detection in urine, and there is no correlation observed between serum and urine anti-THSD7A Abs (R= 0.063, p = 0.604). In addition, urine RBP showed statistically significant relationship with serum PLA2R-Ag (R= 0.239, p < 0.048), eGFR (R= -0.734, p < 0.001) and UPCr index (R= 0.235, p < 0.048). Discussion & conclusion: Serum and urine PLA2R-Ags alongside serum anti-THSD7A Ab could be used in prompt diagnosis and monitoring of primary MGN patients. In addition, urinary RBP and PLA2R-Ag could also be utilised as important tools in treatment decisions and as prognostic indicators of primary MGN, thereby potentially able to prevent the progression to end-stage renal diseases (ESRD).

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