Ir al contenido principal Ir al menú de navegación principal Ir al pie de página del sitio
Revista de la Facultad de Medicina

Vol. 2 Núm. 1 (2024)

Nefritis Lúpica : Una Revisión Sistemática de su Manejo

Artículos de revisión
Publicado: 31-05-2024

Resumen

Introducción: La nefritis lúpica (NL) es una complicación grave del lupus eritematoso sistémico (LES). Afecta principalmente a las mujeres y, en ellas, tiene una tasa de mortalidad seis veces mayor que la población general. La inmunopatología de la NL implica el depósito de complejos inmunes en los glomérulos y su clasificación histopatológica se basa en la biopsia renal.  Objetivos: Evaluar la eficacia y la seguridad de los tratamientos disponibles para la NL en adultos e identificar las intervenciones emergentes para su manejo.  Métodos: Se llevó a cabo una revisión sistemática según las directrices PRISMA, abarcando estudios publicados hasta enero de 2024. La búsqueda se realizó en PubMed, la biblioteca de Cochrane y Google Académico, con dos revisores encargados de la selección y extracción de datos, evaluando el riesgo de sesgo en los ensayos clínicos aleatorizados (ECA) mediante la herramienta Cochrane.  Resultados: Se revisaron 212 artículos, eliminando 31 duplicados y 35 por falta de relevancia. De los 146 restantes, se excluyeron aquellos con defectos en el diseño, objetivos o población inadecuados, quedaron finalmente 31 artículos que cumplían los criterios de inclusión, incluidos 21 estudios analíticos y 10 ECA.  Discusión: Se recomienda el tratamiento inmunosupresor para NL clase III y IV, mientras que para NL clase I o II se evalúa el uso de glucocorticoides con otros agentes inmunosupresores si hay síndrome nefrótico o proteinuria en rango nefrótico. En casos refractarios, terapias emergentes, como guselkumab, ofrecen nuevas perspectivas. Es crucial garantizar una cumplimiento adecuada al tratamiento para maximizar los resultados terapéuticos en estos casos.   Conclusiones: Para el manejo de la NL, se resalta la importancia de reducir la proteinuria y se recomienda hidroxicloroquina (HCQ) para todos estos pacientes. Se sugieren diferentes tratamientos inmunosupresores según la clase de nefritis. La retirada segura de la inmunosupresión es un desafío, requiere de evaluación y seguimiento cercano para evitar riesgos de brotes renales.

Citas

  1. KDIGO Lupud Nephritis Work Group. KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS. Kidney Int. 2024, Jan. 1; 105(1): S1–69. DOI: https://doi.org/10.1016/j.kint.2023.09.002 DOI: https://doi.org/10.1016/j.kint.2023.09.002
  2. Hocaoǧlu, M., Valenzuela-Almada, M.O., Dabit, J.Y., Osei-Onomah, S.A., Chevet, B., Giblon, R.E., et al. Incidence, Prevalence, and Mortality of Lupus Nephritis: A Population-Based Study Over Four Decades Using the Lupus Midwest Network. Arthritis & Rheumatology, 2023, Apr.; 75(4): 567–573. https://doi.org/10.1002/art.42375 DOI: https://doi.org/10.1002/art.42375
  3. Neves, A., Viveiros, L., Venturelli, V., Isenberg, D.A. Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities. Research and Reports in Urology. 2023, July 10; 15: 333–353. https://doi.org/10.2147/RRU.S385836 DOI: https://doi.org/10.2147/RRU.S385836
  4. Parodis, I., Tamirou, F., Houssiau, F.A. Treat-to-Target in Lupus Nephritis. What is the Role of the Repeat Kidney Biopsy? Archivum Immunologiae et Therapiae Experimentalis. (Warsz). 2022, Feb.; 70(1): 8. https://doi.org/10.1007/s00005-022-00646-9 DOI: https://doi.org/10.1007/s00005-022-00646-9
  5. Jourde-Chiche, N., Bobot, M., Burtey, S., Chiche, L., Daugas, E. Weaning Maintenance Therapy in Lupus Nephritis: For Whom, When, and How? Kidney International Reports. 2023, Aug.; 8(8): 1481–1488. https://doi.org/10.1016/j.ekir.2023.05.012 DOI: https://doi.org/10.1016/j.ekir.2023.05.012
  6. Jourde-Chiche, N., Costedoat-Chalumeau, N., Baumstarck, K., Loundou, A., Bouillet, L., Burtey, S., et al. Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial. Ann Rheum Dis. 2022, Oct.; 81(10): 1420–1427. https://doi.org/10.1136/annrheumdis-2022-222435 DOI: https://doi.org/10.1136/annrheumdis-2022-222435
  7. Gasparotto, M,, Gatto, M., Binda, V., Doria, A., Moroni, G. Lupus nephritis: Clinical presentations and outcomes in the 21st century. Rheumatology (Oxford, United Kingdom). 2020 Dec.; 59(Suppl 5): V39–V51. https://doi.org/10.1093/rheumatology/keaa381 DOI: https://doi.org/10.1093/rheumatology/keaa381
  8. Pryor, K.P., Barbhaiya, M., Costenbader, K.H., Feldman, C.H. Disparities in Lupus and Lupus Nephritis Care and Outcomes Among US Medicaid Beneficiaries. Rheumatic Disease Clinics of North America. 2021, Feb.; 47(1): 41–53. https://doi.org/10.1016/j.rdc.2020.09.004 DOI: https://doi.org/10.1016/j.rdc.2020.09.004
  9. Parikh, S.V., Almaani, S., Brodsky, S., Rovin, B.H. Update on Lupus Nephritis: Core Curriculum 2020. American Journal of Kidney Diseases. 2020, Aug; 76(2): 265–281. https://doi.org/10.1053/j.ajkd.2019.10.017 DOI: https://doi.org/10.1053/j.ajkd.2019.10.017
  10. Aponte, I.F., García-Francis, M.V., García-Becerra, J.A., Fuentes-Silva, Y.J., Tovar-Bastidas, D.B., Nieto-Barrios, J.C., et al. Prevalence and factors associated with lupus nephritis in Venezuelan patients. Global Rheumatology. 2021 Sep 23; 1-23. https://www.globalrheumpanlar.org/sites/default/files/archivos/pdf-articulos/2021-09/PDF_Prevalence%20and%20factors%20associated%20with%20lupus%20nephritis%20in%20Venezuelan%20patients..pdf
  11. Gaviria-García, G., Maidana de Zarza, A., Aroca-Martínez, G. Características sociodemográficas y clínicas de pacientes con nefritis lúpica. Barranquilla, Colombia. Mem. Inst. Investig. Cienc. Salud. 2018; 16(2): 32-37. https://doi.org/10.18004/mem.iics/1812-9528/2018.016(02)32-037 DOI: https://doi.org/10.18004/mem.iics/1812-9528/2018.016(02)32-037
  12. Torres-Bustamante, M., Palomino-Suárez, D., Celis, A.M., Nuñez, S.F., Hernández-Sierra, A., et al. Caracterización clínica de pacientes con nefropatía lúpica en Santander, la importancia de la biopsia renal. Rev Colomb Nefrol. 2019, Nov.; 6(2): 122–129. https://pesquisa.bvsalud.org/portal/resource/pt/biblio-1093036 DOI: https://doi.org/10.22265/acnef.6.2.370
  13. Polanco-Flores, A.N., Soto-Abraham,V.M., Castellanos-Roderíguez, F.E. Presentación clínico-patológica de la nefropatía lúpica: experiencia de un centro mexicano. Rev. Colom. Reumatol. 2013, Abr.-Jun.; 20(2): 80-90. https://pesquisa.bvsalud.org/portal/resource/pt/lil-683038 DOI: https://doi.org/10.1016/S0121-8123(13)70002-1
  14. Fatoye, F., Gebrye, T., Mbada, C. Global and regional prevalence and incidence of systemic lupus erythematosus in low-and-middle income countries: a systematic review and meta-analysis. Rheumatology International. 2022, Dec.; 42(12): 2097–2107. https://doi.org/10.1007/s00296-022-05183-4 DOI: https://doi.org/10.1007/s00296-022-05183-4
  15. Cornejo-Guerra, J.A., Lara-Santos, M.J., Méndez-Escobar, E. Caracterización clínica y terapéutica de pacientes con nefropatía asociada a Lupus eritomatoso sistémico. Estudio descriptivo realizado en pacientes mayores de 8 años, que asistieron durante el 2000 al 2010, a Consulta Externa de Reumatología en los Hospitales: General San Juan de Dios, Instituto Guatemalteco de Seguridad Social y Clínicas Privadas de Reumatología de la ciudad de Guatemala [Tesis de Graduación Licenciatura]. Guatemala: Universidad San Carlos de Guatemala, Facultad de Medicina; 2010. http://biblioteca.usac.edu.gt/tesis/05/05_8718.pdf
  16. Benavides, A., Rodríguez, C., Toledo, D., Girón, E., Pérez, E., Pineda, M., et al. Prevalencia de enfermedad glomerular en el Hospital General San Juan de Dios, Guatemala. Revista médica (Colegio de Médicos y Cirujanos de Guatemala). 2021, Dec.; 160(3): 237–241. DOI: https://doi.org/10.36109/rmg.v160i3.441 DOI: https://doi.org/10.36109/rmg.v160i3.441
  17. Anders, H.J., Saxena, R., Zhao, M.H., Parodis, I., Salmon, J.E., Mohan, C. Lupus nephritis. Nat Rev Dis Primers. 2020, Jan.; 6(1):7. https://doi.org/10.1038/s41572-019-0141-9 DOI: https://doi.org/10.1038/s41572-019-0141-9
  18. Weening, J.J., D’Agati, V.D., Schwartz, M.M., Seshan, S.V., Alpers, C.E., Appel, G.B., et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004, Feb.; 65(2): 521–530. https://doi.org/10.1111/j.1523-1755.2004.00443.x DOI: https://doi.org/10.1111/j.1523-1755.2004.00443.x
  19. Karagiannis, M., Drouzas, K., Liapis, G., Lionaki, S. Lupus Nephritis: Clinical Picture, Histopathological Diagnosis, and Management. Open access peer-reviewed chapter. 2023, Jan. 30. DOI: 10.5772/intechopen.109498 DOI: https://doi.org/10.5772/intechopen.109498
  20. Rethlefsen, M.L., Kirtley, S., Waffenschmidt, S., Ayala, A.P., Moher, D., Page, M.J., et al. PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. Syst Rev. 2021, Jan.; 10(1):39. https://doi.org/10.1186/s13643-020-01542-z DOI: https://doi.org/10.1186/s13643-020-01542-z
  21. McGuinness, L.A., Higgins, J.P.T. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021, Jan.; 12(1): 55–61. https://doi.org/10.1002/jrsm.1411 DOI: https://doi.org/10.1002/jrsm.1411
  22. Singh, J.A., Hossain, A., Kotb, A., Oliveira, A., Mudano, A.S., Grossman, J., et al. Treatments for lupus nephritis: A systematic review and network metaanalysis. Journal of Rheumatology. 2016, Oct.; 43(10): 1801–1815. https://doi.org/10.3899/jrheum.160041 DOI: https://doi.org/10.3899/jrheum.160041
  23. Chen, Y., Sun, J., Zou, K., Yang, Y., Liu, G. Treatment for lupus nephritis: an overview of systematic reviews and meta-analyses. Rheumatol Int. 2017, Jul.; 37(7): 1089–1099. https://doi.org/10.1007/s00296-017-3733-2 DOI: https://doi.org/10.1007/s00296-017-3733-2
  24. Kostopoulou, M., Fanouriakis, A., Cheema, K., Boletis, J., Bertsias, G., Jayne, D., et al. Management of lupus nephritis: A systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations. RMD Open. 2020, Jul.; 6(2): e001263. https://doi.org/10.1136/rmdopen-2020-001263 DOI: https://doi.org/10.1136/rmdopen-2020-001263
  25. Steiger, S., Ehreiser, L., Anders, J., Anders, H.J. Biological drugs for systemic lupus erythematosus or active lupus nephritis and rates of infectious complications. Evidence from large clinical trials. Front Immunol. 2022, Sept.; 13:999704. https://doi.org/10.3389/fimmu.2022.999704 DOI: https://doi.org/10.3389/fimmu.2022.999704
  26. Chen, P., Zhou, Y., Wu, L., Chen, S., Han, F. Efficacy and Safety of Biologic Agents for Lupus Nephritis: A Systematic Review and Meta-analysis. Journal of Clinical Rheumatology. 2023, Mar.; 29(2): 95–100. https://doi.org/10.1097/RHU.0000000000001877 DOI: https://doi.org/10.1097/RHU.0000000000001877
  27. Lee, Y.H., Song, G.G. Comparative Efficacy and Safety of Biological Agents in the Treatment of Lupus Nephritis: A Network Meta-Analysis. Pharmacology. 2023, Nov.; 108(1): 17–26. https://doi.org/10.1159/000527223 DOI: https://doi.org/10.1159/000527223
  28. Palmer, S.C., Tunnicliffe, D.J., Singh-Grewal, D., Mavridis, D., Tonelli, M., Johnson, D.W., et al. Induction and maintenance immunosuppression treatment of proliferative lupus nephritis: a network meta-analysis of randomized trials. American Journal of Kidney Diseases. 2017, Sept.; 70(3): 324–336. https://doi.org/10.1053/j.ajkd.2016.12.008 DOI: https://doi.org/10.1053/j.ajkd.2016.12.008
  29. Tang KT, Tseng CH, Hsieh TY, Chen DY. Induction therapy for membranous lupus nephritis: a systematic review and network meta-analysis. Int J Rheum Dis. 2018, Jun.; 21(6): 1163–1172. https://doi.org/10.1111/1756-185X.13321 DOI: https://doi.org/10.1111/1756-185X.13321
  30. Kraaij, T., Bredewold, O.W., Trompet, S., Huizinga, T.W.J., Rabelink, T., Teng, Y.K.O., et al. Tac-Tic Use of Tacrolimus-Based Regimens in Lupus Nephritis. Lupus Science & Medicine 2016, Dec.; 3(1): e000169. https://doi.org/10.1136/lupus-2016-000169 DOI: https://doi.org/10.1136/lupus-2016-000169
  31. Hannah J, Casian A, D’Cruz D. Tacrolimus use in lupus nephritis: A systematic review and meta-analysis. Autoimmun Rev. 2016, Dec.; 15(1): 93–101. https://doi.org/10.1016/j.autrev.2015.09.006 DOI: https://doi.org/10.1016/j.autrev.2015.09.006
  32. Tian, M., Song, X., Dong, L., Xin, X., Dong, J. Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis. Medicine (United States). 2017, Dec.; 96(51): e9408. https://doi.org/10.1097/MD.0000000000009408 DOI: https://doi.org/10.1097/MD.0000000000009408
  33. Li, Y., Xu, S., Xu, G. Comparison of Different Uses of Cyclophosphamide in Lupus Nephritis: A Meta-Analysis of Randomized Controlled Trials. Endocr Metab Immune Disord Drug Targets. 2020; 20(5): 687–702. https://doi.org/10.2174/1871530319666191107110420 DOI: https://doi.org/10.2174/1871530319666191107110420
  34. Jiang, Y.P., Zhao, X.X., Chen, R.-R., Xu, Z.H., Wen, C.P., Yu, J. Comparative efficacy and safety of mycophenolate mofetil and cyclophosphamide in the induction treatment of lupus nephritis: A systematic review and meta-analysis. Medicine (Baltimore, United States). 2020, Sep.; 99(38): e22328. https://doi.org/10.1097/MD.0000000000022328 DOI: https://doi.org/10.1097/MD.0000000000022328
  35. Yuan, Z., Xie, Q., Wu, X., Tan, B., Zhang X. Rituximab treatment for lupus nephritis: A systematic review. Clinical and Investigative Medicine. 2020, Jun.; 43(2): E47–54. https://doi.org/10.25011/cim.v43i2.33864 DOI: https://doi.org/10.25011/cim.v43i2.33864
  36. Li, K., Yu, Y., Gao, Y., Zhao, F., Liang, Z., Gao, J. Comparative Effectiveness of Rituximab and Common Induction Therapies for Lupus Nephritis: A Systematic Review and Network Meta-Analysis. Front Immunol. 2022, Apr.; 13: 859380. https://doi.org/10.3389/fimmu.2022.859380 DOI: https://doi.org/10.3389/fimmu.2022.859380
  37. Joy, A., Muralidharan, A., Alfaraj. M,, Shantharam, D., Cherukuri, A.S.S., Muthukumar, A. The Role of Belimumab in Systemic Lupus Erythematosis: A Systematic Review. Cureus. 2022, Jun.; 14(6): e25887. https://doi.org/10.7759/cureus.25887 DOI: https://doi.org/10.7759/cureus.25887
  38. Shrestha, S., Budhathokim, P., Adhikari, Y., Marasini, A., Bhandari, S., Mir, W.A.Y., et al. Belimumab in Lupus Nephritis: A Systematic Review and Meta-Analysis. Cureus. 2021, Dec.; 13(12): e20440. https://doi.org/10.7759/cureus.20440 DOI: https://doi.org/10.7759/cureus.20440
  39. Cajamarca-Barón, J., Buitrago-Bohórquez, J., Mendoza Orozco, J.E., Segura, O., Guavita-Navarro, D., Gallego-Cardona, L., et al. Efficacy and safety of intravenous immunoglobulin in patients with lupus nephritis: A systematic review of the literature. Autoimmun Rev. 2022, Nov.; 21(11): 103182. https://doi.org/10.1016/j.autrev.2022.103182 DOI: https://doi.org/10.1016/j.autrev.2022.103182
  40. Arriens, C., Teng, Y.K.O., Ginzler, E.M., Parikh, S.V., Askanase, A.D., Saxena, A., et al. Update on the efficacy and safety profile of voclosporin: an integrated analysis of clinical trials in lupus nephritis. Arthritis Care Res (Hoboken). 2023, Jul.; 75(7): 1399–1408. https://doi.org/10.1002/acr.25007 DOI: https://doi.org/10.1002/acr.25007
  41. Rovin, B.H., Teng, Y.K.O., Ginzler, E.M., Arriens, C., Caster, D.J., Romero-Diazm J., et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet. 2021, May; 397(10289): 2070–2080. https://doi.org/10.1016/S0140-6736(21)00578-X DOI: https://doi.org/10.1016/S0140-6736(21)00578-X
  42. Rovin, B.H., Solomons, N., Pendergraft, W.F., Dooley, M.A., Tumlin, J, Romero-Diaz J, et al. A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int. 2019, Jan.; 95(1): 219–231. https://doi.org/10.1016/j.kint.2018.08.025 DOI: https://doi.org/10.1016/j.kint.2018.08.025
  43. Zheng, Z., Zhang, H., Peng, X., Zhang, C., Xing. C., Xu, G., et al. Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients with Lupus Nephritis: A Randomized Clinical Trial. JAMA Netw Open. 2022, Mar.; 5(3): e224492. https://doi.org/10.1001/jamanetworkopen.2022.4492 DOI: https://doi.org/10.1001/jamanetworkopen.2022.4492
  44. Mok, C.C., Ho, L.Y., Ying, S.K.Y., Leung, M.C., To, C.H., Ng, W.L. Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis. Ann Rheum Dis. 2020, Aug.; 79(8): 1070–1076. https://doi.org/10.1136/annrheumdis-2020-217178 DOI: https://doi.org/10.1136/annrheumdis-2020-217178
  45. Furie, R., Rovin, B.H., Houssiau, F., Malvar, A., Teng, Y.K.O., Contreras, G., et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020, Sep.; 383(12): 1117–1128. https://doi.org/10.1056/NEJMoa2001180 DOI: https://doi.org/10.1056/NEJMoa2001180
  46. Yu, X., Chen, N., Xue, J., Mok, C.C., Bae, S.C., Peng, X., et al. Efficacy and Safety of Belimumab in Patients With Lupus Nephritis: Subgroup Analyses of a Phase 3 Randomized Trial in the East Asian Population. American Journal of Kidney Diseases. 2023, Mar.; 81(3): 294-306.e1. https://doi.org/10.1053/j.ajkd.2022.06.013 DOI: https://doi.org/10.1053/j.ajkd.2022.06.013
  47. Atisha-Fregoso, Y., Malkiel, S., Harris, K.M., Byron, M., Ding, L., Kanaparthi, S., et al. Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. Arthritis and Rheumatology. 2021, Jan.; 73(1): 121–131. https://doi.org/10.1002/art.41466 DOI: https://doi.org/10.1002/art.41466
  48. Fu, Q., Wu, C., Dai, M., Wang, S., Xu, J., Dai, L., et al. Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up. Ann Rheum Dis. 2022, Nov.; 81(11): 1549–1555. https://doi.org/10.1136/ard-2022-222486 DOI: https://doi.org/10.1136/ard-2022-222486
  49. Furie, R.A., Aroca, G., Cascino, M.D., Garg, J.P., Rovin, B.H., Alvarez, A., et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022, Jan.; 81(1): 100–107. https://doi.org/10.1136/annrheumdis-2021-220920 DOI: https://doi.org/10.1136/annrheumdis-2021-220920

  • María Isabel Bojorquez Ortiz
    Facultad de Medicina, Universidad Francisco Marroquín
  • Izabel Paola Hernández Cabrera
    Facultad de Medicina, Universidad Francisco Marroquín
Palabras clave: nefritis lúpica clasificación histopatológica tratamiento inhibidores de calcineurina anticuerpos monoclonales inmunosupresión

Cómo citar

Bojorquez Ortiz, M. I., & Hernández Cabrera, I. P. (2024). Nefritis Lúpica : Una Revisión Sistemática de su Manejo. Revista De La Facultad De Medicina, 2(1), 46–67. https://doi.org/10.37345/23045329.v2i1.115