rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2016-543-552rsp-2300Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПРОБЛЕМЫ ДИАГНОСТИКИ И ЛЕЧЕНИЯ АНЦА-АССОЦИИРОВАННЫХ СИСТЕМНЫХ ВАСКУЛИТОВ: В ФОКУСЕ АНЦА-НЕГАТИВНЫЙ PAUCI-ИММУННЫЙ ГЛОМЕРУЛОНЕФРИТPROBLEMS IN THE DIAGNOSIS AND TREATMENT OF ANCA-ASSOCIATED SYSTEMIC VASCULITIS: IN THE FOCUS OF ANCA-NEGATIVE PAUCI-IMMUNE GLOMERULONEPHRITISБекетоваТ. В.BeketovaT. V.

1115522 Москва, Каширское шоссе, 34А

Tatyana Beketova.

134A, Kashirskoe Shosse, Moscow

TVBEKTVBEK@rambler.ruФроловаН. Ф.FrolovaN. F.

2123182 Москва, ул. Пехотная, 3

115522; 23, Pekhotnaya St., Moscow 123182

СтоляревичЕ. С.StolyarevichE. S.

2123182 Москва, ул. Пехотная, 3

115522; 23, Pekhotnaya St., Moscow 123182

ВолковМ. Ю.VolkovM. Yu.

1115522 Москва, Каширское шоссе, 34А

134A, Kashirskoe Shosse, Moscow

КотенкоО. Н.KotenkoO. N.

2123182 Москва, ул. Пехотная, 3

115522; 23, Pekhotnaya St., Moscow 123182

АлександроваЕ. Н.AleksandrovaE. N.

1115522 Москва, Каширское шоссе, 34А

134A, Kashirskoe Shosse, Moscow

Научно-исследовательский институт ревматологии имени В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationГородская клиническая больница №52РоссияCity Clinical Hospital Fifty-TwoRussian Federation201609122016545543552Copyright © Бекетова Т.В., Фролова Н.Ф., Столяревич Е.С., Волков М.Ю., Котенко О.Н., Александрова Е.Н., 20162016Бекетова Т.В., Фролова Н.Ф., Столяревич Е.С., Волков М.Ю., Котенко О.Н., Александрова Е.Н.Beketova T.V., Frolova N.F., Stolyarevich E.S., Volkov M.Y., Kotenko O.N., Aleksandrova E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2300

Одной из наиболее распространенных причин  быстропрогрессирующего гломерулонефрита (ГН) является так называемый pauci-иммунный (малоиммунный) ГН с полулуниями, который  характеризуется отсутствием свечения  в образцах ткани почки при иммунофлюоресцентной микроскопии и присутствием  гиперпродукции антинейтрофильных цитоплазматических антител (АНЦА). Вместе с тем в ряде случаев pauci-иммунного ГН АНЦА в сыворотке  крови отсутствуют. На основании собственного опыта наблюдения авторами представлена  клинико-морфологическая характеристика больных АНЦА-негативным pauci-иммунным ГН и проанализированы данные литературы.

Материал и методы

Материал и методы. В ретроспективное исследование вошли 8 пациентов с АНЦА-негативным pauci-иммунным ГН, которые с 2011 по 2015 г. наблюдались  в двух российских  центрах, нефрологическом и ревматологическом.

Результаты и обсуждение

Результаты и обсуждение. По нашим  данным,  у 6% пациентов с АНЦА-ассоциированным системным  васкулитом (СВ) с поражением почек и/или pauci-иммунным ГН АНЦА не определяются. Средний  возраст начала заболевания у АНЦА-негативных больных составил 50±18 лет (от 19 до 74 лет), соотношение мужчин и женщин  – 1:1. В четырех случаях (50%) диагностирован микроскопический полиангиит, в двух – гранулематоз с полиангиитом, еще у двух пациентов присутствовало  изолированное поражение  почек. Бирмингемский  индекс активности СВ в среднем составил 19,6±7,9.  Гематурия наблюдалась во всех случаях и у четверых была массивной. Средняя  суточная протеинурия – 3,4±2,7  г, у троих пациентов (38%) отмечен нефротический синдром.  Средний  уровень креатинина крови – 704±405 мкмоль/л, у шести пациентов (75%) ГН характеризовался быстропрогрессирующим течением,  и пяти потребовалось лечение гемодиализом. В большинстве случаев при морфологическом исследовании почки определялись полулуния (в среднем в 52% клубочков), у одного больного – гломерулосклероз. У всех пациентов отмечался разной  степени выраженности фиброз интерстиция. В результате лечения  в 3 случаях (38%) была достигнута ремиссия.  Частота летальных исходов составила 38%. Интересно, что данные нашей группы, так же как и полученные в европейских когортах, имели некоторые  отличия от исследований, проведенных  в Азии, по данным  которых при биопсии  почки чаще выявляли  клубочки с полулуниями, была выше протеинурия и хуже «почечная выживаемость».

Таким образом,  в 3–39%  случаев pauci-иммунного ГН с полулуниями в сыворотке  крови отсутствуют АНЦА, но клинико-морфологическая картина  соответствует АНЦА-ассоциированному СВ. Биопсия почки помогает установить верный  диагноз,  своевременно назначить  индукционное лечение и улучшить прогноз.

One of the most common  causes of rapidly progressive glomerulonephritis (GN)  is the so-called pauci-immune crescentic GN that is characterized  by no luminescence  in kidney tissue samples during immunofluorescence microscopy and by the hyperproduction of antineutrophil cytoplasmic antibodies (ANCA). At the same time, serum ANCAs are absent in a number of cases of pauci-immune GN. Based on their own experience, the authors present the clinical and morphological characteristics of patients with ANCA-negative  pauci-immune GN and analyze the data available in the literature.

Subjects and methods. This retrospective study included 8 patients with ANCA-negative  pauci-immune GN,  who were followed up at two Russian centers (the Center of Nephrology and the Center of Rheumatology) in 2011 to 2015. Results and discussion. According to our data, ANCAs are not detectable in 6% of the patients with ANCA-associated systemic vasculitis (SV) with renal involvement and/or pauci-immune GN.  The mean age at onset of the disease in the ANCA-negative  patients was 50±18 years (range 19 to 74 years); the male/female  ratio was 1:1. Four (50%) cases were diagnosed with microscopic polyangiitis; 2 cases had granulomatosis with polyangiitis; isolated renal injury was present in other 2 patients. The Birmingham SV activity index averaged 19.6±7.9.  Hematuria  was observed in all cases and it was massive in 4. The mean daily urinary protein level was 3.4±2.7 g; three (38%) patients were observed to have nephrotic  syndrome. The blood creatinine  level averaged 704±405 μmol/l;  GN was characterized  by a rapidly progressive course in 6 (75%) patients; hemodialysis was needed in 5. A morphological study of the kidney determined  crescents (in on an average of 52 glomeruli) in the majority of cases and glomerulosclerosis in one patient. All the patients were observed to have varying degrees of interstitial fibrosis. Three (38%) treated patients achieved remission. The mortality rates were 38%. Interestingly,  the data from our group as well those obtained by the study of European  cohorts were slightly different from those of the studies conducted  in Asia, according to which a renal biopsy more frequently revealed glomerular crescents; the levels of protein in the urine were higher and renal survival was worse.

Thus, serum ANCAs are absent in 3–39% of cases of pauci-immune crescentic GN,  but the clinical and morphological picture corresponds to ANCA-associated  SV. A kidney biopsy helps establish the correct diagnosis, timely use induction  treatment, and improve prognosis.

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The authors declare that there are no conflicts of interest present.