Clinical and morphological presentation of C3 glomerulopathy: a single-center study of 60 cases

Abstract

INTRODUCTION. СЗ-glomerulopathy (СЗ-GP) is a spectrum of diseases caused by dysregulation of the alternative complement pathway. The present study was carried out taking into account the limited number of foreign and the absence of original studies in the Russian population.THE AIM. Analysis of clinical and morphological manifestations of СЗ-GP at the time of primary diagnosis.PATIENTS AND METHODS. Retrospective analysis of the etiology, clinical data and morphology of СЗ-GP identified in the period 2006-2021.RESULTS. The study included 60 cases. The average age of patients is 4З±17 years. Nephrotic syndrome was detected in 47 % of patients; in 58 % of cases the estimated glomerular filtration rate was <60 ml/ min/иЗ m2. The dominant morphological pattern was membranoproliferative glomerulonephritis (75% cases). In 2 cases, СЗ-GP debuted with clinical and morphological manifestations of the disease of minimal changes, in which the identification of characteristic electron-dense deposits became obvious when performing a second biopsy. 4 cases had at the onset classical signs of complement-mediated thrombotic microangiopathy (atypical hemolytic uremic syndrome) in combination with C3-GP or its subsequent development.Ultrastructural examination was performed in 40 cases. 8 patients (20%) were diagnosed dense deposit disease, 32 patients - C3-glomerulonephritis. Primary C3-GP was detected in 87 % of patients, secondary - in 13 % (monoclonal gammopathies - 10 %, autoimmune diseases - 3 %).Increased level of antibodies to factor H was detected in 2 of 12 patients who underwent this study. Nucleotide variants of unknown clinical significance in complement genes were detected in 2 out of 6 patients during molecular genetic testing.CONCLUSION. C3-GP is a severe variant of glomerular damage with a heterogeneous etiological structure, which requires the use of ultrastructural and molecular diagnostics, as well as clinical analysis and identification of pathogenetic mechanisms to determine approaches to therapy.