A multidisciplinary approach to the diagnosis and treatment of concomitant mycobacterial and fungal pulmonary infection in end-stage chronic kidney disease patient with ANCA-associated systemic vasculitis on renal replacement therapy. Case report

Non-tuberculous pulmonary mycobacteriosis causes difficulties in both diagnosis and treatment due to the absence of reference laboratories in most thoracic clinics, the natural resistance of non-tuberculous mycobacteria to antibacterial drugs, and a large number of adverse events (AE) relative with medications prescribed for treatment this pathology. The pulmonary invasive aspergillosis was previously described as an infection associated with the risk of fatal complications and requires the administration of the antifungal therapy and a decrease in the immunosuppression intensity. End stage chronic kidney disease patients are one of the most vulnerable groups for concomitant respiratory infections, and the tolerability of antibacterial and antifungal drugs among this population need the further studies. That clinical case reflects the period of intensive phase of full- antimycobacterial therapy of pulmonary mycobacteriosis with co-infection - aspergillosis against the background of the biological anti-B cell therapy beginning of ANCA-associated vasculitis in a patient receiving replacement hemodialysis therapy. Administration of antibacterial drugs such as ethambutol 1.2 / b.i.d., rifampicin 0.45 / b.i.d moxifloxacin 0.4 / b.i.d, protionamide 0.5 / b.i.d. to a 55-year-old patient undergoing hemodialysis programmed with hepatoprotective agents, neurometabolic “protection”, taking iron-, calcium-, erythropoietin - containing drugs was associated with the occurrence of AE such as allergic skin rashes and dyspeptic symptoms (nausea, vomiting, diarrhea), which required dose adjustment, and subsequently, the discontinuation of protionamide. The identification of Aspergillus fungi growth by culture in fluid of bronchoalveolar lavage (BAL), required local endobronchial injection of voriconazole into the bronchus leading to cavity, taking into account the patient`s immunocompromised status, to prevent the occurrence of invasive pulmonary aspergillosis. This combined treatment caused a stabilization of chest CT changes (compaction and calcification of 2 cavities). At the same time, there was observed an increase of level BUN in serum and thrombocytopenia, which regarded as ANCA-associated glomerulonephritis progression and required the appointment of a genetically engineered anti-B-cell biotherapy with rituximab in rheumatological hospital. Combined therapy led to further positive clinical and radiological dynamics, normalization of indicators of clinical, biochemical blood tests, and a general improvement in the patient's well-being. Thus, this case demonstrates that the treatment of concomitant respiratory infections in such patients is associated with great difficulties with interpretation X-ray-laboratory tests, prescribing of drugs, AEs, and requires a multidisciplinary approach from different specialists.

гемодиализ, ANCA-ассоциированные васкулиты, микобактериоз легких, аспергиллез, диагностика, лечение, бронхоскопия, БАЛ, hemodialysis, ANCA-associated vasculitis, pulmonary mycobacteriosis, aspergillosis, diagnosis, treatment, bronchoscopy, BAL

1. Шмелев Е. И, Ковалевская М. Н., Эргешов А.Э. и др. Микобактериозы в практике врача-пульмонолога: состояние проблемы. Практическая пульмонология. 2016; 3: 37-42.

2. Бикбов Б.Т., Томилина Н.А. Ранее выявление хронической болезни почек: маркер преемственности в лечении пациентов, влияние на выживаемость и кардиоваскулярную летальность больных на диализе. Российский медицинский журнал. 2014. 1:12-17.

3. Томилина Н. А., Андрусев А.М., Перегудова Н.Г. и др. Заместительная терапия терминальной хронической почечной недостаточности в Российской Федерации в 2010-2015 гг. Отчет по данным Общероссийского Регистра заместительной почечной терапии Российского диализного общества. Нефрология и диализ. 2017;19 (4): 2-94.

4. Гордеева О. М., Карпина Н. Л. Диагностика туберкулеза у больных с терминальной стадией хронической болезни почек. Врач. 2020: 31 (2): 23-29.

5. Neirynck N., Vanholder R., Schepers E. et al. An update on uremic toxins. Int Urol Nephrol. 2013; 45: 139-150.

6. Fournier A., Birmele B., Francois M. et al. Factors associated with albumin loss in post-dilution hemodiafiltration. Int J Artif Organs. 2015; 38: 76-82.

7. Gayrard N., Ficheux A., Duranton F. et al. Correction: Consequences of increasing convection onto patient care and protein removal in hemodialysis. PLoS One. 2018; 13 (1)

8. Anders H.J., Andersen K., Stecher B. The intestinal microbiota, a leaky gut and abnormal immunity in kidney disease. Kidney Int. 2013; 83:1010-1016.

9. Stubbs J.R., Idiculla A., Slusser J. et al. Cholecalciferol supplementation alters calcitriol-responsive monocyte proteins and decreases inflamatory cytokines in ESRD. J Am Soc Nephrol.2010; 21: 353-361.

10. Sakina B. Naqvi and Allan J. Collins. Infectious Complications in Chronic Kidney Disease. Advances in Chronic Kidney Disease. 2006; 13 (3): 199-204.

11. Bertrand L. Bacterial infections in hemodialysis patients: Pathogenesis and prevention. Kidney International. 2005; 67: 2508-2519.

12. Ashley C. and Dunleavy A. The Renal Drug Handbook. 5th Edition.2019; 1- 1109.

13. Stabler S., Giovannelli J., Launay D., et al. Serious infectious events and immunoglobulin replacement therapy in patients with autoimmune diseases receiving rituximab: a retrospective cohort study, Clinical Infectious Diseases. 2020: ciaa127.

14. Бекетова Т. В., Александрова Е. Н., Новоселова Т.М. и др. Российский опыт применения моноклональных антител к В-лимфоцитам (ритуксимаб) при системных васкулитах, ассоциированных с антинейтрофильными цитоплазматическими антителами (предварительные результаты российского регистра НОРМА). Научно-практическая ревматология.2014; 52 (2): 147-158.

15. Du Rand I.A. et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults Thorax.2013; 68: 1-44.

16. Patterson T.F., Thompson G.R., Denning D.W. et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2016; 63 (4): 1-60