Clinical significance of antibodies to the M-type phospholipase A2 receptor in patients with primary membranous nephropathy

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Aim

To evaluate the significance of circulating antibodies to the M-type phospholipase A2 receptor (anti-PLA2R) in the diagnosis of primary membranous nephropathy (MN) and the determination of the clinical features of the disease.

Material and methods

155 adult patients with primary MN (112 men and 43 women, median age 51 [36; 58] years) were included. The control group consisted of 16 patients with other morphological variants of nephropathy. AntiPLA2R serum levels were determined by indirect immunofluorescence. Anti-PLA2R titers <1:10 were considered as reference values. The risk of primary MN progression was assessed based on the severity of proteinuria, renal dysfunction, the presence of life-threatening complications of nephrotic syndrome (NS) and anti-PLA2R titer.

Results

Anti-PLA2R were tested on average 10 months after detection of high proteinuria. Anti-PLA2R were positive in 94 (60.6%) patients with primary MN in various titers: 1:20 (n=13), 1:40 (n=16), 1:80 (n=28), 1:160 (n=20), 1:320 (n=12) and 1:640 (n=5). None of the patients were anti-PLA2R positive in the control group. Anti-PLA2R-positive patients had higher proteinuria and were more likely to have NS and impaired renal function (chronic kidney disease stage 3 and higher). In patients with medium and high anti-PLA2R titers (≥1:160), daily urinary protein excretion and creatinine levels were statistically significantly higher, whereas albuminemia was lower than in patients with low anti-PLA2R titers. In antiPLA2R-positive group, more patients had high and very high risk of progression of primary MN (p=0.002).

Conclusion

Delayed anti-PLA2R testing of patients with NS may explain a lower frequency of anti-PLA2R positivity compared to that in the other studies. Our results confirm the value of anti-PLA2R for MN diagnosis, assessment of disease activity and optimization of treatment. Anti-PLA2R testing should be widely implemented into clinical practice.

Key words

Membranous nephropathy, PLA2R, nephrotic syndrom