Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana

Objetivo: Evaluar el impacto de la plasmaféresis en pacientes con vasculitis ANCA y compromiso renal, en particular su efecto sobre la mortalidad o la progresión a enfermedad renal crónica terminal (ERCT). Métodos: Estudio retrospectivo multicéntrico que incluyó a pacientes con vasculitis ANCA y niv...

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Autores:
Rodelo Ceballos, Joaquin Roberto
Aguirre Hernandez, Lina Marcela
Carvajal Quiroz, Jose Nelson
Restrepo Escobar, Mauricio
Tipo de recurso:
Tesis
Fecha de publicación:
2025
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
spa
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/46790
Acceso en línea:
https://hdl.handle.net/10495/46790
Palabra clave:
Plasmaferesis
Plasmapheresis
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Fallo Renal Crónico
Kidney Failure, Chronic
https://id.nlm.nih.gov/mesh/D010956
https://id.nlm.nih.gov/mesh/D056648
https://id.nlm.nih.gov/mesh/D007676
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
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openAccess
License
http://creativecommons.org/licenses/by-nc-sa/4.0/
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network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
dc.title.translated.none.fl_str_mv Plasma Exchange in ANCA-Associated Vasculitis with Kidney Involvement: Who Truly Benefits? Outcomes from a Colombian Cohort
title Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
spellingShingle Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
Plasmaferesis
Plasmapheresis
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Fallo Renal Crónico
Kidney Failure, Chronic
https://id.nlm.nih.gov/mesh/D010956
https://id.nlm.nih.gov/mesh/D056648
https://id.nlm.nih.gov/mesh/D007676
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
title_short Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
title_full Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
title_fullStr Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
title_full_unstemmed Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
title_sort Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombiana
dc.creator.fl_str_mv Rodelo Ceballos, Joaquin Roberto
Aguirre Hernandez, Lina Marcela
Carvajal Quiroz, Jose Nelson
Restrepo Escobar, Mauricio
dc.contributor.advisor.none.fl_str_mv Rodelo Ceballos, Joaquin Roberto
dc.contributor.author.none.fl_str_mv Rodelo Ceballos, Joaquin Roberto
Aguirre Hernandez, Lina Marcela
Carvajal Quiroz, Jose Nelson
Restrepo Escobar, Mauricio
dc.contributor.researchgroup.none.fl_str_mv Grupo de Reumatología Universidad de Antioquia -GRUA-
dc.contributor.jury.none.fl_str_mv Atencia Florez, Carlos Jose
Rubio Elorza, Liliana Maria
dc.subject.decs.none.fl_str_mv Plasmaferesis
Plasmapheresis
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Fallo Renal Crónico
Kidney Failure, Chronic
topic Plasmaferesis
Plasmapheresis
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Fallo Renal Crónico
Kidney Failure, Chronic
https://id.nlm.nih.gov/mesh/D010956
https://id.nlm.nih.gov/mesh/D056648
https://id.nlm.nih.gov/mesh/D007676
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D010956
https://id.nlm.nih.gov/mesh/D056648
https://id.nlm.nih.gov/mesh/D007676
dc.subject.ods.none.fl_str_mv ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
description Objetivo: Evaluar el impacto de la plasmaféresis en pacientes con vasculitis ANCA y compromiso renal, en particular su efecto sobre la mortalidad o la progresión a enfermedad renal crónica terminal (ERCT). Métodos: Estudio retrospectivo multicéntrico que incluyó a pacientes con vasculitis ANCA y niveles de creatinina sérica ≥1.5mg/dl. Se compararon los desenlaces clínicos entre aquellos tratados con plasmaféresis y los que recibieron tratamiento estándar. El desenlace primario fue la mortalidad o progresión a ERCT, mientras que los desenlaces secundarios incluyeron infecciones intrahospitalarias, necesidad de diálisis y recuperación renal. Resultados: En pacientes con creatinina sérica ≥5.7 mg/dl, el uso de plasmaféresis se asoció con una reducción significativa del riesgo de enfermedad renal crónica terminal a los 12 meses de seguimiento con una disminución del 62% ( HR 0.38 ( CI 95% 0.14 -0.97; P= 0.04). Sin embargo, no se observó beneficio en pacientes con creatinina <5.7 mg/dl, y se evidenció un aumento significativo del riesgo de infecciones intrahospitalarias (OR ajustado 4.66; IC 95%: 1.89–11.5; p = 0.001). Este riesgo se incrementó en los pacientes con deterioro renal avanzado, con un OR de 17.8 (p = 0.006). Conclusiones: La plasmaféresis mostró un efecto protector en pacientes con niveles elevados de creatinina (>5.7 mg/dl), reduciendo el riesgo de enfermedad renal crónica terminal. No se observaron beneficios en pacientes con creatinina más baja, y se identificó un mayor riesgo de infecciones intrahospitalarias, especialmente en aquellos con mayor deterioro renal. Se requieren estudios prospectivos para confirmar estos hallazgos y definir criterios más precisos para el uso de plasmaféresis en este contexto
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-07-17T17:25:29Z
dc.date.issued.none.fl_str_mv 2025
dc.type.none.fl_str_mv Trabajo de grado - Especialización
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url https://hdl.handle.net/10495/46790
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dc.relation.references.none.fl_str_mv 1. Kronbichler A, Bajema IM, Bruchfeld A, Mastroianni Kirsztajn G, Stone JH. Diagnosis and management of ANCA-associated vasculitis. Lancet. 2024 Feb 17;403(10427):683-698
2. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11
3. Jain K, Jawa P, Derebail VK, Falk RJ. Treatment Updates in Antineutrophil Cytoplasmic Autoantibodies (ANCA) Vasculitis. Kidney360. 2021 Apr;2(4):763-770
4. Geetha D, Jefferson JA. ANCA-Associated Vasculitis: Core Curriculum 2020. Am J Kidney Dis. 2020 Jan;75(1):124-137
5. Harper L, Morgan MD, Walsh M, Hoglund P, Westman K, Flossmann O, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012 Jun;71(6):955-60
6. Wallace ZS, Fu X, Harkness T, Stone JH, Zhang Y, Choi H. All-cause and cause-specific mortality in ANCA-associated vasculitis: overall and according to ANCA type. Rheumatology (Oxford). 2020 Sep 1;59(9):2308-2315
7. Tan JA, Dehghan N, Chen W, Xie H, Esdaile JM, Avina-Zubieta JA. Mortality in ANCA-associated vasculitis: ameta-analysis of observational studies. Ann Rheum Dis. 2017 Sep;76(9):1566-1574
8. Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, et al. European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007 Jul;18(7):2180-8
9. Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13;382(7):622-631
10. Cole E, Cattran D, Magil A, Greenwood C, Churchill D, Sutton D, et al. A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group. Am J Kidney Dis. 1992 Sep;20(3):261-9
11. Almaani S, Fussner LA, Brodsky S, Meara AS, Jayne D. ANCA-Associated Vasculitis: An Update. J Clin Med. 2021 Apr 1;10(7):1446
12. Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis. 2011 Apr;57(4):566-74
13. Walters GD, Willis NS, Craig JC. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol. 2010 Jun 24;11:12
14. Zeng L, Walsh M, Guyatt GH, Siemieniuk RAC, Collister D, Booth M, et al. Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline. BMJ. 2022 Feb 25;376: e064597
15. Kidney Disease: Improving Global Outcomes (KDIGO) ANCA Vasculitis Work Group. KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Kidney Int. 2024 Mar;105(3S): S71-S116
16. Robson JC, Grayson PC, Ponte C, Suppiah R, Craven A, Judge A, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis with Polyangiitis. Arthritis Rheumatol. 2022 Mar;74(3):393-399
17. Suppiah R, Robson JC, Grayson PC, Ponte C, Craven A, Khalid S, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis. Arthritis Rheumatol. 2022 Mar;74(3):400-406
18. Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994 Nov;87(11):671-8
19. Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, et al. Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021 Nov 4;385(19):1737-1749
20. Cortazar FB, Niles JL. The Fate of Plasma Exchange and Glucocorticoid Dosing in ANCA-Associated Vasculitis After PEXIVAS. Am J Kidney Dis. 2020 Oct;76(4):595-597
21. Morales E, Rúa-Figueroa I, Callejas Rubio JL, Ávila Bernabéu A, Blanco Alonso R, Cid Xutgla MC, et al. Recommendations for the diagnosis and treatment of anti-neutrophil cytoplasmic autoantibody associated vasculitis. Nefrologia (Engl Ed). 2025 Jan;45(1):15-58
22. Walsh M, Collister D, Zeng L, Merkel PA, Pusey CD, Guyatt G, et al; Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis BMJ Rapid Recommendations Group. The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis. BMJ. 2022 Feb 25;376:e064604
23. Wing EJ, Bruns FJ, Fraley DS, Segel DP, Adler S. Infectious complications with plasmapheresis in rapidly progressive glomerulonephritis. JAMA. 1980 Nov 28;244(21):2423-6
24. Szpirt WM, Heaf JG, Petersen J. Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener's granulomatosis--a clinical randomized controlled trial. Nephrol Dial Transplant. 2011 Jan;26(1):206-13
25. Fodil S, Urbina T, Bredin S, Mayaux J, Lafarge A, Missri L, et al. Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10-year multicentric study. Ann Intensive Care. 2024 Jul 29;14(1):117
26. Ross C, Makhzoum JP, Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol. 2022 Jul;9(3):153-166
27. Monti S, Brandolino F, Milanesi A, Xoxi B, Delvino P, Montecucco C. Novel Therapies for ANCA-associated Vasculitis. Curr Rheumatol Rep. 2021 Apr 28;23(6):38
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dc.publisher.faculty.none.fl_str_mv Facultad de Medicina
dc.publisher.branch.none.fl_str_mv Campus en el Área de la salud
publisher.none.fl_str_mv Universidad de Antioquia
institution Universidad de Antioquia
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spelling Rodelo Ceballos, Joaquin RobertoRodelo Ceballos, Joaquin RobertoAguirre Hernandez, Lina MarcelaCarvajal Quiroz, Jose NelsonRestrepo Escobar, MauricioGrupo de Reumatología Universidad de Antioquia -GRUA-Atencia Florez, Carlos JoseRubio Elorza, Liliana Maria2025-07-17T17:25:29Z2025https://hdl.handle.net/10495/46790Objetivo: Evaluar el impacto de la plasmaféresis en pacientes con vasculitis ANCA y compromiso renal, en particular su efecto sobre la mortalidad o la progresión a enfermedad renal crónica terminal (ERCT). Métodos: Estudio retrospectivo multicéntrico que incluyó a pacientes con vasculitis ANCA y niveles de creatinina sérica ≥1.5mg/dl. Se compararon los desenlaces clínicos entre aquellos tratados con plasmaféresis y los que recibieron tratamiento estándar. El desenlace primario fue la mortalidad o progresión a ERCT, mientras que los desenlaces secundarios incluyeron infecciones intrahospitalarias, necesidad de diálisis y recuperación renal. Resultados: En pacientes con creatinina sérica ≥5.7 mg/dl, el uso de plasmaféresis se asoció con una reducción significativa del riesgo de enfermedad renal crónica terminal a los 12 meses de seguimiento con una disminución del 62% ( HR 0.38 ( CI 95% 0.14 -0.97; P= 0.04). Sin embargo, no se observó beneficio en pacientes con creatinina <5.7 mg/dl, y se evidenció un aumento significativo del riesgo de infecciones intrahospitalarias (OR ajustado 4.66; IC 95%: 1.89–11.5; p = 0.001). Este riesgo se incrementó en los pacientes con deterioro renal avanzado, con un OR de 17.8 (p = 0.006). Conclusiones: La plasmaféresis mostró un efecto protector en pacientes con niveles elevados de creatinina (>5.7 mg/dl), reduciendo el riesgo de enfermedad renal crónica terminal. No se observaron beneficios en pacientes con creatinina más baja, y se identificó un mayor riesgo de infecciones intrahospitalarias, especialmente en aquellos con mayor deterioro renal. Se requieren estudios prospectivos para confirmar estos hallazgos y definir criterios más precisos para el uso de plasmaféresis en este contextoObjective: This study aimed to evaluate the impact of plasma exchange in patients with antineutrophil cytoplasmic antibody (ANCA) – associated vasculitis and kidney involment, specifically its effect on mortality or progression to end stage kidney disease (ESKD). Methods: We conducted a multicenter retrospective study including patients with ANCA associated vasculitis and serum creatinine level ≥1.5mg/dl. Clinical outcomes were compared between those threated with plasma exchange and those received standard therapy. The primary outcome was the composite of mortality or progression to ESKD. Secondary outcomes included in -hospital infections, need for dialysis and kidney function recovery. Results: Among patients with serum creatinine ≥5.7mg/dl, plasma exchange was associated with a significant reduction in the progression to ESKD, with a 62% reduction. However, no benefit was observed in patients with creatinine <5.7mg/dL, and a significant increase in the risk of in hospital infections was identified (adjusted odds ratio 4.66; 95% confidence interval [CI], 1.89 to 11.5; p=0.001). This risk was further elevated in patients with advance renal impairment, with and odds ratio of 17.8 (P =0.006) Conclusions: Plasma exchange demonstrated a protective effect in patients with markedly elevated serum creatinine levels (>5.7mg/dl), reducing de risk of progression to end stage kidney disease. No clinical benefit was observed in patients with lower creatinine levels, and an increased risk of in hospital infections was noted, particularly among those with more advanced renal dysfunction. Prospective studies are warranted to confirm these findings and to define more precise criteria for the use of plasma exchange in these settingsReumatologíaCOL0010959EspecializaciónEspecialista en Nefrología36 paginasapplication/pdfspaUniversidad de AntioquiaEspecialización en NefrologíaDepartamento de Medicina InternaMedellín, ColombiaFacultad de MedicinaCampus en el Área de la saludhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Impacto de la plasmaféresis en vasculitis asociada a ANCA con compromiso renal : experiencia clínica en una cohorte colombianaPlasma Exchange in ANCA-Associated Vasculitis with Kidney Involvement: Who Truly Benefits? Outcomes from a Colombian CohortTrabajo de grado - Especializaciónhttp://purl.org/coar/resource_type/c_46echttp://purl.org/redcol/resource_type/COtherTexthttp://purl.org/coar/version/c_b1a7d7d4d402bcceinfo:eu-repo/semantics/otherinfo:eu-repo/semantics/draft1. Kronbichler A, Bajema IM, Bruchfeld A, Mastroianni Kirsztajn G, Stone JH. Diagnosis and management of ANCA-associated vasculitis. Lancet. 2024 Feb 17;403(10427):683-6982. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-113. Jain K, Jawa P, Derebail VK, Falk RJ. Treatment Updates in Antineutrophil Cytoplasmic Autoantibodies (ANCA) Vasculitis. Kidney360. 2021 Apr;2(4):763-7704. Geetha D, Jefferson JA. ANCA-Associated Vasculitis: Core Curriculum 2020. Am J Kidney Dis. 2020 Jan;75(1):124-1375. Harper L, Morgan MD, Walsh M, Hoglund P, Westman K, Flossmann O, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012 Jun;71(6):955-606. Wallace ZS, Fu X, Harkness T, Stone JH, Zhang Y, Choi H. All-cause and cause-specific mortality in ANCA-associated vasculitis: overall and according to ANCA type. Rheumatology (Oxford). 2020 Sep 1;59(9):2308-23157. Tan JA, Dehghan N, Chen W, Xie H, Esdaile JM, Avina-Zubieta JA. Mortality in ANCA-associated vasculitis: ameta-analysis of observational studies. Ann Rheum Dis. 2017 Sep;76(9):1566-15748. Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, et al. European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007 Jul;18(7):2180-89. Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13;382(7):622-63110. Cole E, Cattran D, Magil A, Greenwood C, Churchill D, Sutton D, et al. A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group. Am J Kidney Dis. 1992 Sep;20(3):261-911. Almaani S, Fussner LA, Brodsky S, Meara AS, Jayne D. ANCA-Associated Vasculitis: An Update. J Clin Med. 2021 Apr 1;10(7):144612. Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis. 2011 Apr;57(4):566-7413. Walters GD, Willis NS, Craig JC. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol. 2010 Jun 24;11:1214. Zeng L, Walsh M, Guyatt GH, Siemieniuk RAC, Collister D, Booth M, et al. Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline. BMJ. 2022 Feb 25;376: e06459715. Kidney Disease: Improving Global Outcomes (KDIGO) ANCA Vasculitis Work Group. KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Kidney Int. 2024 Mar;105(3S): S71-S11616. Robson JC, Grayson PC, Ponte C, Suppiah R, Craven A, Judge A, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis with Polyangiitis. Arthritis Rheumatol. 2022 Mar;74(3):393-39917. Suppiah R, Robson JC, Grayson PC, Ponte C, Craven A, Khalid S, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis. Arthritis Rheumatol. 2022 Mar;74(3):400-40618. Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994 Nov;87(11):671-819. Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, et al. Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021 Nov 4;385(19):1737-174920. Cortazar FB, Niles JL. The Fate of Plasma Exchange and Glucocorticoid Dosing in ANCA-Associated Vasculitis After PEXIVAS. Am J Kidney Dis. 2020 Oct;76(4):595-59721. Morales E, Rúa-Figueroa I, Callejas Rubio JL, Ávila Bernabéu A, Blanco Alonso R, Cid Xutgla MC, et al. Recommendations for the diagnosis and treatment of anti-neutrophil cytoplasmic autoantibody associated vasculitis. Nefrologia (Engl Ed). 2025 Jan;45(1):15-5822. Walsh M, Collister D, Zeng L, Merkel PA, Pusey CD, Guyatt G, et al; Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis BMJ Rapid Recommendations Group. The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis. BMJ. 2022 Feb 25;376:e06460423. Wing EJ, Bruns FJ, Fraley DS, Segel DP, Adler S. Infectious complications with plasmapheresis in rapidly progressive glomerulonephritis. JAMA. 1980 Nov 28;244(21):2423-624. Szpirt WM, Heaf JG, Petersen J. Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener's granulomatosis--a clinical randomized controlled trial. Nephrol Dial Transplant. 2011 Jan;26(1):206-1325. Fodil S, Urbina T, Bredin S, Mayaux J, Lafarge A, Missri L, et al. Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10-year multicentric study. Ann Intensive Care. 2024 Jul 29;14(1):11726. Ross C, Makhzoum JP, Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol. 2022 Jul;9(3):153-16627. Monti S, Brandolino F, Milanesi A, Xoxi B, Delvino P, Montecucco C. Novel Therapies for ANCA-associated Vasculitis. Curr Rheumatol Rep. 2021 Apr 28;23(6):38PlasmaferesisPlasmapheresisVasculitis Asociada a Anticuerpos Citoplasmáticos AntineutrófilosAnti-Neutrophil Cytoplasmic Antibody-Associated VasculitisFallo Renal CrónicoKidney Failure, Chronichttps://id.nlm.nih.gov/mesh/D010956https://id.nlm.nih.gov/mesh/D056648https://id.nlm.nih.gov/mesh/D007676ODS 3: Salud y bienestar. 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