Clinical and genetic features of idiopathic membranous nephropathy in russian patients


I.A. Bobyleva, P.A. Kakhsurueva, E.S. Kamyshova, I.N. Bobkova, O.A. Li, A.M. Kuchieva, E.E. Filatova, E.V. Zakharova, A.G. Borisov

1) Sechenov First Moscow State Medical University; Moscow, Russia 2) S.P. Botkin City Clinical Hospital of the Moscow Healthcare Department; Moscow, Russia 3) Burdenko Main Military Clinical Hospital; Moscow, Russia
Objective. Evaluation of the clinical features of idiopathic membranous nephropathy (IMN) in Russian patients depending on seropositivity for antibodies to the M-type phospholipase A2 receptor (anti-PLA2R), as well as the association between anti-PLA2R and polymorphic markers rs4664308 of the PLA2R1 gene and rs2187668 of the HLA-DQA1gene.
Material and methods. Clinical and laboratory parameters of 34 patients with IMN at the time of nephrobiopsy, the severity of morphological changes and the response to immunosuppressive therapy depending on the presence of anti-PLA2R were analyzed; genotyping of polymorphic markers rs4664308 of the PLA2R1 gene and rs2187668 of the HLA-DQA1gene compared with 100 healthy control subjects was performed.
Results. Anti-PLA2R positivity was associated with a later manifestation of the disease (anti-PLA2R “+”: 53 [27–77] years; anti-PLA2R “-” 40 [22–54] years; p=0.013); duration of IMN before nephrobiopsy was comparable in both groups. There were no statistically significant differences in seropositive and seronegative groups in terms of blood pressure, kidney function, and frequency of nephrotic syndrome (NS); in patients with anti-PLA2R positivity, however, there was a tendency to more frequent detection of proteinuria (PU) >4 g/day (76 and 37.5%, respectively; p=0.080). An association of the studied polymorphic markers with an increased risk of developing IMN was found: for the A/A genotype of the rs4664308 polymorphic marker of the PLA2R1 gene, the odds ratio [OR] was 3.88 (95% confidence interval [CI] – 1.69–8.94; p<0.001 ), and for the A/A genotype of the rs2187668 polymorphic marker of the HLA gene, the OR reached 8.75 (95% CI – 1.61–47.55; p=0.010). Anti-PLA2R “+” patients showed a tendency towards more frequent carriage of the A/A genotype of the polymorphic marker rs4664308 of the PLA2R1 gene associated with an increased risk of development of IMN (p=0.052).
Conclusion. The relationship between the presence of anti-PLA2R and the clinical and laboratory features of IMN was shown. Variants of the PLA2R1 and HLA-DQA1 genes associated with an increased risk of development of IMN were identified, with
a tendency to a higher frequency of the PLA2R1 gene A/A genotype in anti-PLA2R-positive patients.

About the Autors


Irina A. Bobyleva – Postgraduate Student at the Department of Internal Diseases, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, Sechenov First MSMU; Moscow, Russia.
Patimat A. Kakhsurueva – Postgraduate Student at the Department of Internal Diseases, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, Sechenov First MSMU; Moscow, Russia.
Elena S. Kamyshova – Associate Professor at the Department of Internal Diseases, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, Sechenov First MSMU; Moscow, Russia.
Irina N. Bobkova – Doctor of Medical Sciences, Professor at the Department of Internal Diseases, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, Sechenov First MSMU; Moscow, Russia.
Olga A. Li – Teaching Assistant at the Department of Internal Diseases, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, Sechenov First MSMU; Moscow, Russia.
Agunda M. Kuchieva – Nephrologist at the Artificial Kidney Department, Clinic for Rheumatology, Internal and Occupational Diseases named after E.M. Tareev, Sechenov First MSMU; Moscow, Russia.
Ekaterina E. Filatova – Resident Physician at the Department of Internal Diseases, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, Sechenov First MSMU; Moscow, Russia.
Elena V. Zakharova – Head of the Department of Nephrology №. 24, S.P. Botkin City Clinical Hospital of the Moscow Healthcare Department; Moscow, Russia.
Aleksey G. Borisov – Head of the Department of Nephrology, Burdenko Main Military Clinical Hospital; Moscow, Russia.


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