Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022
La nefritis lúpica (NL) es la complicación más frecuente y grave del Lupus Eritematoso Sistémico (LES), evoluciona a enfermedad renal terminal en aproximadamente 10 % de los pacientes, siendo uno de los principales determinantes de la clasificación histológica. La biopsia es el patrón oro para el di...
- Autores:
-
Araque Libreros, Sarai Elena
Ali Salloum, Waeel Yamil
- Tipo de recurso:
- Fecha de publicación:
- 2023
- Institución:
- Universidad Libre
- Repositorio:
- RIU - Repositorio Institucional UniLibre
- Idioma:
- OAI Identifier:
- oai:repository.unilibre.edu.co:10901/27875
- Acceso en línea:
- https://hdl.handle.net/10901/27875
- Palabra clave:
- Nefritis lúpica
Sedimento Urinario
Proteinuria
Creatinina
Hospitalización
Lupus nephritis
Urinary sediment
Proteinuria
Creatinine
Hospitalization
Nefritis lúpica
Proteinuria
Enfermedades renales
Lupus eritematoso sistémico
- Rights
- License
- http://purl.org/coar/access_right/c_abf2
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RULIBRE2 |
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RIU - Repositorio Institucional UniLibre |
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| dc.title.spa.fl_str_mv |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| title |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| spellingShingle |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 Nefritis lúpica Sedimento Urinario Proteinuria Creatinina Hospitalización Lupus nephritis Urinary sediment Proteinuria Creatinine Hospitalization Nefritis lúpica Proteinuria Enfermedades renales Lupus eritematoso sistémico |
| title_short |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| title_full |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| title_fullStr |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| title_full_unstemmed |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| title_sort |
Relación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022 |
| dc.creator.fl_str_mv |
Araque Libreros, Sarai Elena Ali Salloum, Waeel Yamil |
| dc.contributor.advisor.none.fl_str_mv |
Aroca Martínez, Gustavo Varela, Lourdes |
| dc.contributor.author.none.fl_str_mv |
Araque Libreros, Sarai Elena Ali Salloum, Waeel Yamil |
| dc.subject.spa.fl_str_mv |
Nefritis lúpica Sedimento Urinario Proteinuria Creatinina Hospitalización |
| topic |
Nefritis lúpica Sedimento Urinario Proteinuria Creatinina Hospitalización Lupus nephritis Urinary sediment Proteinuria Creatinine Hospitalization Nefritis lúpica Proteinuria Enfermedades renales Lupus eritematoso sistémico |
| dc.subject.subjectenglish.spa.fl_str_mv |
Lupus nephritis Urinary sediment Proteinuria Creatinine Hospitalization |
| dc.subject.lemb.spa.fl_str_mv |
Nefritis lúpica Proteinuria Enfermedades renales Lupus eritematoso sistémico |
| description |
La nefritis lúpica (NL) es la complicación más frecuente y grave del Lupus Eritematoso Sistémico (LES), evoluciona a enfermedad renal terminal en aproximadamente 10 % de los pacientes, siendo uno de los principales determinantes de la clasificación histológica. La biopsia es el patrón oro para el diagnóstico, no obstante, dadas las limitaciones, se estudian marcadores otros séricos y urinarios que pueden realizar un abordaje menos invasivo. Objetivo: Analizar la relación entre el grado de proteinuria y sedimento urinario activo con enfermedad proliferativa y exacerbación en pacientes con nefritis lúpica de un centro de referencia del caribe colombiano entre enero 2013 y diciembre 2022. Metodología: Se presenta un estudio retrospectivo, basado en el análisis de las características clínicas, parámetros bioquímicos y urinarios de pacientes con NL del programa de LES en una Clínica de Barranquilla. Se realizó una prueba de normalidad, a las variables continuas se les hicieron estadísticas descriptivas y las cualitativas se representaron en frecuencias absolutas y porcentaje. Se realizó una regresión logística para cálculo de OR, la significancia fue de p < 0.05. Resultados: En este estudio se evaluaron 96 participantes. Al comparar las clases histopatológicas, se encontró una relación positiva de los subtipos proliferativos con mayor grado de proteinuria, sedimento urinario activo, mayor puntuación del SLEDAI-2K, elevación de creatinina y el índice de cronicidad, no se estableció una relación estadísticamente significativa entre un sedimento urinario activo o la severidad de la proteinuria con riesgo superior de agudización y hospitalización. Por su parte, se anticipa que, por cada unidad de aumento en la creatinina, los pacientes tienen 2.25 veces más probabilidades de ser hospitalizados. Conclusión: Estos hallazgos indican que la presencia de proteinuria y sedimento urinario activo es superior en pacientes con subtipos proliferativos de enfermedad, sin embargo, no se relacionan con mayor riesgo de hospitalización. Por otro lado, la elevación de los niveles de creatinina sérica resultó ser una variable que se relaciona con una mayor frecuencia de hospitalización y debe alertar al clínico a un cambio en el abordaje terapéutico para prevenir resultados clínicos desfavorables. |
| publishDate |
2023 |
| dc.date.accessioned.none.fl_str_mv |
2023-12-13T21:03:04Z |
| dc.date.available.none.fl_str_mv |
2023-12-13T21:03:04Z |
| dc.date.created.none.fl_str_mv |
2023-07 |
| dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_7a1f |
| dc.type.local.spa.fl_str_mv |
Tesis de Especialización |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10901/27875 |
| url |
https://hdl.handle.net/10901/27875 |
| dc.relation.references.spa.fl_str_mv |
Murimi-Worstell IB, Lin DH, Kan H, Tierce J, Wang X, Nab H, et al. Healthcare Utilization and Costs of Systemic Lupus Erythematosus by Disease Severity in the United States. J Rheumatol [Internet]. 2021 Mar;48(3):385–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32611669 Singh S, Saxena R. Lupus nephritis. Am J Med Sci [Internet]. 2009 Jun;337(6):451–60. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/19390431 Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev. 2010 Mar;9(5): A277-87 Calixto O-J, Vargas-Zambrano J-C, Franco J-S, Molano-Gonzalez N, Salazar J-C, Rodríguez-Jiménez M, et al. El costo de la atención ambulatoria del lupus eritematoso sistémico en Colombia. Contrastes y comparaciones con otras poblaciones. 2015;1–66. Available from: http://repository.urosario.edu.co/handle/10336/10533 Ruiz-Irastorza G, Espinosa G, Frutos MA, Jiménez-Alonso J, Praga M, Pallarés L, et al. Diagnosis and treatment of Lupus nephritis: Consensus document from the systemic auto-immune disease group (GEAS) of the Spanish society of internal medicine (SEMI) and the Spanish society of nephrology (S.E.N.). Nefrologia. 2012;32(SUPPL. 1):1–45 Torres-bustamante M, Suárez DP-, Celis AM, Nuñez SF, Hernández-sierra A. Caracterización clínica de pacientes con nefropatía lúpica en Santander, la importancia de la biopsia renal Clinical and epidemiological characterization of patients with lupus nephropathy in Santander, Colombia: the importance of the renal biopsy. 2019;6(2):122–9 Contreras G, Pardo V, Cely C, Borja E, Hurtado A, De La Cuesta C, et al. Factors associated with poor outcomes in patients with lupus nephritis. Lupus [Internet]. 2005;14(11):890–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16335581 Rovin BH, Zhang X. Biomarkers for lupus nephritis: the quest continues. Clin J Am Soc Nephrol [Internet]. 2009 Nov;4(11):1858–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19729426 Perazella MA. The urine sediment as a biomarker of kidney disease. Am J Kidney Dis [Internet]. 2015 Nov;66(5):748–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25943719 Avihingsanon Y, Phumesin P, Benjachat T, Akkasilpa S, Kittikowit V, Praditpornsilpa K, et al. Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int [Internet]. 2006 Feb;69(4):747–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16518330 El-Shehaby A, Darweesh H, El-Khatib M, Momtaz M, Marzouk S, ElShaarawy N, et al. Correlations of urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and IL-8 with lupus nephritis. J Clin Immunol [Internet]. 2011 Oct;31(5):848–56. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21691937 Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol [Internet]. 2018 Jan 26;3(19). Available from: http://www.ncbi.nlm.nih.gov/pubmed/29374079 Zickert A, Sundelin B, Svenungsson E, Gunnarsson I. Role of early repeated renal biopsies in lupus nephritis. Lupus Sci Med. 2014;1(1): e000018 Malvar A, Pirruccio P, Alberton V, Lococo B, Recalde C, et al. Histologic versus clinical remission in proliferative lupus nephritis. Nephrol Dial Transplant. 2017 Ago 1;32(8):1338-1344 Kim SJ, Lee K, Diamond B. Follicular Helper T Cells in Systemic Lupus Erythematosus. Front Immunol [Internet]. 2018; 9:1793. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30123218 Zharkova O, Celhar T, Cravens PD, Satterthwaite AB, Fairhurst A-M, Davis LS. Pathways leading to an immunological disease: systemic lupus erythematosus. Rheumatology (Oxford) [Internet]. 2017;56(suppl_1):i55–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28375453 Stojan G, Petri M. Epidemiology of systemic lupus erythematosus: an update. Curr Opin Rheumatol [Internet]. 2018 Mar;30(2):144–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29251660 Feldman CH, Hiraki LT, Liu J, Fischer MA, Solomon DH, Alarcón GS, et al. Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000-2004. Arthritis Rheum. 2013 Mar;65(3):753–63 Jakes RW, Bae S-C, Louthrenoo W, Mok C-C, Navarra S V, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken) [Internet]. 2012 Feb;64(2):159–68. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22052624 Seligman VA, Lum RF, Olson JL, Li H, Criswell LA. Demographic differences in the development of lupus nephritis: A retrospective analysis. Am J Med. 2002;112:726–9 Díaz-Coronado JC, Rojas-Villarraga A, Hernandez-Parra D, BetancurVásquez L, Lacouture-Fierro J, Gonzalez-Hurtado D, et al. Clinical and sociodemographic factors associated with lupus nephritis in Colombian patients: A cross-sectional study. Reumatol Clin. 2021;17(6):351–6 Kuo C-F, Grainge MJ, Valdes AM, See L-C, Luo S-F, Yu K-H, et al. Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families. JAMA Intern Med [Internet]. 2015 Sep;175(9):1518–26. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26193127 Imgenberg-Kreuz J, Carlsson Almlöf J, Leonard D, Alexsson A, Nordmark G, Eloranta M-L, et al. DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus. Ann Rheum Dis [Internet]. 2018 May;77(5):736–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29437559 Deng Y, Tsao BP. Updates in Lupus Genetics. Curr Rheumatol Rep. 2017 Nov;19(11):68 Lyn-Cook BD, Xie C, Oates J, Treadwell E, Word B, Hammons G, et al. Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol [Internet]. 2014 Sep;61(1):38–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24865418 Rother N, van der Vlag J. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Front Immunol [Internet]. 2015;6:610. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26648939 Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J, Edens M, et al. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell [Internet]. 2016 Apr 21;165(3):551–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27040498 Vinay K, MD A. Patología estructural funcional. 2018 Yu ASL, Chertow GM, Luyckx VA, Marsden PA, Skorecki K, Taal MW, et al. EL RIÑÓN. ultima ed Weening JJ, D’Agati VD, Schwartz MM, Seshan S V, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int [Internet]. 2004 Feb;65(2):521–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14717922 Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018;93(4):789–96 Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost [Internet]. 2006 Feb;4(2):295–306. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16420554 Schwartz MM, Lan SP, Bernstein J, Hill GS, Holley K, Lewis EJ. Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis [Internet]. 1993 Apr;21(4):374–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8465815 Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) [Internet]. 2012 Jun;64(6):797–808. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22556106 Gasparotto M, Gatto M, Binda V, Doria A, Moroni G. Lupus nephritis: clinical presentations and outcomes in the 21st century. Rheumatology [Internet]. 2020 Dec 5;59(Supplement_5):v39–51. Available from: https://academic.oup.com/rheumatology/article/59/Supplement_5/v39/60247 33 Hu W, Chen Y, Wang S, Chen H, Liu Z, Zeng C, et al. Clinical-Morphological Features and Outcomes of Lupus Podocytopathy. Clin J Am Soc Nephrol [Internet]. 2016 Apr 7;11(4):585–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26983707 Anders H-J, Saxena R, Zhao M-H, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Prim [Internet]. 2020 Jan 23;6(1):7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31974366 Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med [Internet]. 2008 Feb 28;358(9):929–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18305268 Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Sep;71(9):1400–12 Appel GB, Cohen DJ, Pirani CL, Meltzer JI, Estes D. Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization. Am J Med [Internet]. 1987 Nov;83(5):877–85. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3674094 Waldman M, Madaio MP. Pathogenic autoantibodies in lupus nephritis. Lupus [Internet]. 2005 Jan 2;14(1):19–24. Available from: http://journals.sagepub.com/doi/10.1191/0961203305lu2054oa Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med [Internet]. 2000 Jan;124(1):71–81. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10629135 Martínez-Martínez MU, Llamazares-Azuara LM de G, Martínez-Galla D, Mandeville PB, Valadez-Castillo F, Román-Acosta S, et al. Urinary sediment suggests lupus nephritis histology. Lupus [Internet]. 2017 May;26(6):580–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27687029 Yuan M, Tan Y, Li J, Yu X, Zhang H, Zhao M. Urinary sediments could differentiate endocapillary proliferative lupus nephritis and endocapillary proliferative IgA nephropathy. Int Immunopharmacol [Internet]. 2021 Jan;90:107122. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33199236 Bihl GR, Petri M, Fine DM. Kidney biopsy in lupus nephritis: look before you leap. Nephrol Dial Transplant [Internet]. 2006 Jul;21(7):1749–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16632559 Aragón CC, Tafúr R-A, Suárez-Avellaneda A, Martínez MT, Salas A de Las, Tobón GJ. Urinary biomarkers in lupus nephritis. J Transl Autoimmun [Internet]. 2020;3:100042. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32743523 Reyes-Martínez F, Pérez-Navarro M, Rodríguez-Matías A, Soto-Abraham V, Gutierrez-Reyes G, Medina-Avila Z, et al. Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study. Nefrologia [Internet]. 2018;38(2):152–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28755900 Salem MN, Taha HA, Abd El-Fattah El-Feqi M, Eesa NN, Mohamed RA. Urinary TNF-like weak inducer of apoptosis (TWEAK) as a biomarker of lupus nephritis. Z Rheumatol [Internet]. 2018 Feb;77(1):71–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27619369 Nalbandian A, Crispín JC, Tsokos GC. Interleukin-17 and systemic lupus erythematosus: current concepts. Clin Exp Immunol [Internet]. 2009 Aug;157(2):209–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19604260 Crispín JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol [Internet]. 2008 Dec 15;181(12):8761–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19050297 Su H, Lei C-T, Zhang C. Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol [Internet]. 2017;8:405. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28484449 Richards HB, Satoh M, Shaw M, Libert C, Poli V, Reeves WH. Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. J Exp Med [Internet]. 1998 Sep 7;188(5):985–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9730900 wano M, Dohi K, Hirata E, Kurumatani N, Horii Y, Shiiki H, et al. Urinary levels of IL-6 in patients with active lupus nephritis. Clin Nephrol [Internet]. 1993 Jul;40(1):16–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8358870 Stewart AG, Thomas B, Koff J. TGF-β: Master regulator of inflammation and fibrosis. Respirology [Internet]. 2018 Dec;23(12):1096–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30284753 Kiani AN, Johnson K, Chen C, Diehl E, Hu H, Vasudevan G, et al. Urine osteoprotegerin and monocyte chemoattractant protein-1 in lupus nephritis. J Rheumatol [Internet]. 2009 Oct;36(10):2224–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19648301 Tesch GH. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol [Internet]. 2008 Apr;294(4):F697-701. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18272603 Kim MJ, Tam FWK. Urinary monocyte chemoattractant protein-1 in renal disease. Clin Chim Acta [Internet]. 2011 Nov 20;412(23–24):2022–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21851811 Gonzalez-Aparicio M, Alfaro C. Influence of Interleukin-8 and Neutrophil Extracellular Trap (NET) Formation in the Tumor Microenvironment: Is There a Pathogenic Role? J Immunol Res [Internet]. 2019;2019:6252138. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31093511 Rovin BH, Lu L, Zhang X. A novel interleukin-8 polymorphism is associated with severe systemic lupus erythematosus nephritis. Kidney Int [Internet]. 2002 Jul;62(1):261–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12081586 Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis [Internet]. 2008 Sep;52(3):595–605. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18725016 Malyszko J, Malyszko JS, Bachorzewska-Gajewska H, Poniatowski B, Dobrzycki S, Mysliwiec M. Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients. Transplant Proc [Internet]. 2009;41(1):158–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19249502 Satirapoj B, Kitiyakara C, Leelahavanichkul A, Avihingsanon Y, Supasyndh O. Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis. BMC Nephrol [Internet]. 2017 Aug 4;18(1):263. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28778196 Genctoy G, Arikan S. Urinary N-Acetyl-Beta-D Glucosaminidase Activity is Associated with Inflammation and Proteinuria in Diabetic and Non-Diabetic Patients with Different Stages of Chronic Kidney Disease. Turkish Nephrol Dial Transplant [Internet]. 2015 May 18;24(2):166–73. Available from: http://turkjnephrol.org/en/urinary-n-acetyl-beta-d-glucosaminidase-activity-isassociated-with-inflammation-and-proteinuria-in-diabetic-and-non-diabeticpatients-with-different-stages-of-chronic-kidney-disease-135690 Erdener D, Aksu K, Biçer I, Doğanavşargil E, Kutay FZ. Urinary N-acetyl-betaD-glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis. J Clin Lab Anal [Internet]. 2005;19(4):172–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16025478 Ward MM. Cardiovascular and cerebrovascular morbidity and mortality among women with end-stage renal disease attributable to lupus nephritis. Am J Kidney Dis. 2000;36:516–25 Ward MM. Cardiovascular and cerebrovascular morbidity and mortality among women with end-stage renal disease attributable to lupus nephritis. Am J Kidney Dis [Internet]. 2000 Sep;36(3):516–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10977783 Contreras G, Mattiazzi A, Guerra G, Ortega LM, Tozman EC, Li H, et al. Recurrence of lupus nephritis after kidney transplantation. J Am Soc Nephrol [Internet]. 2010 Jul;21(7):1200–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20488956 Norby GE, Strøm EH, Midtvedt K, Hartmann A, Gilboe I-M, Leivestad T, et al. Recurrent lupus nephritis after kidney transplantation: a surveillance biopsy study. Ann Rheum Dis [Internet]. 2010 Aug;69(8):1484–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20498208 Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF, American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology [Internet]. 2016 Jun;123(6):1386–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26992838 Fanouriakis A, Kostopoulou M, Cheema K, Anders H-J, Aringer M, Bajema I, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis [Internet]. 2020 Jun;79(6):713–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32220834 Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis [Internet]. 2019 Jun;78(6):736–45. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30926722 Ruiz-Irastorza G, Espinosa G, Frutos MA, Jiménez-Alonso J, Praga M, Pallarés L, et al. Diagnóstico y tratamiento de la nefritis lúpica. Nefrologia. 2012 Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) [Internet]. 2012 Jun;64(6):797–808. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22556106 Grootscholten C, Ligtenberg G, Hagen EC, van den Wall Bake AWL, de GlasVos JW, Bijl M, et al. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int [Internet]. 2006 Aug;70(4):732–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16820790 ACCESS Trial Group. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol (Hoboken, NJ) [Internet]. 2014 Nov;66(11):3096–104. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25403681 Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido E de R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: The EuroLupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum [Internet]. 2002 Aug;46(8):2121–31. Available from: http://doi.wiley.com/10.1002/art.10461 Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med [Internet]. 2001 Aug 21;135(4):248–57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11511139 Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol [Internet]. 2009 May;20(5):1103–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19369404 Cortés-Hernández J, Torres-Salido MT, Medrano AS, Tarrés MV, Ordi-Ros J. Long-term outcomes--mycophenolate mofetil treatment for lupus nephritis with addition of tacrolimus for resistant cases. Nephrol Dial Transplant [Internet]. 2010 Dec;25(12):3939–48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20538787 Rovin BH, Solomons N, Pendergraft WF, Dooley MA, 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 [Internet]. 2019 Jan;95(1):219– 31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30420324 Ward M, Tektonidou MG. Belimumab as Add-on Therapy in Lupus Nephritis. N Engl J Med [Internet]. 2020 Sep 17;383(12):1184–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32937052 Sahin GM, Sahin S, Kiziltas S, Masatlioglu S, Oguz F, Ergin H. Mycophenolate mofetil versus azathioprine in the maintenance therapy of lupus nephritis. Ren Fail. 2008;30(9):865–9 Mart GA, Gonz HJ. Nefritis lúpica. (11 Coronado Juan, Rojas Adriana, Hernandez Deicy. Clinical and sociodemographic factors associated whit nephritis in colombian patients: a cross-seccional study. reumatol Clin. 2019: p. 1-6 Mendez Tatiana, Posso Ivan, Nieto Ivanna. Utility of anti-C1q and antinucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia. Rev colomb reumatol. 2020; 28 (1): p. 1-7 gladel Mendez Tatiana, Posso Ivan, Nieto Ivanna. Utility of anti-C1q and antinucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia. Rev colomb reumatol. 2020; 28 (1): p. 1-7 Torres-bustamante M, Suárez DP-, Celis AM, Nuñez SF, Hernández-sierra A. Caracterización clínica de pacientes con nefropatía lúpica en Santander, la importancia de la biopsia renal Clinical and epidemiological characterization of patients with lupus nephropathy in Santander, Colombia: the importance of the renal biopsy. 2019;6(2):122–9 Pinto LF, Guerra L, González JR, Pérez A, Velásquez CJ, Felipe O, et al. Lupus Eritematoso Sistémico: análisis del comportamiento clínico en una población de Medellín. Rev Col Reum 1997; 4:170-173 Martínez-Martínez MU, Llamazares-Azuara LM, Martínez-Galla D, Mandeville PB, Valadez-Castillo F, Román-Acosta S, Borjas-García JA, Abud-Mendoza C. Urinary sediment suggests lupus nephritis histology. Lupus. 2017; 26(6): p. 580-587 Velasquez Carlos, Colina Yerlin, Correa Sara. Clinicopathological relationship in colombia patients with lupus nephritis. Rev colomb reumatol. 2017; 24 (4): 211-218 Zickert A, Sundelin B, Svenungsson E, Gunnarsson I. Role of early repeated renal biopsies in lupus nephritis. 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Aroca Martínez, GustavoVarela, LourdesAraque Libreros, Sarai ElenaAli Salloum, Waeel YamilBarranquilla2023-12-13T21:03:04Z2023-12-13T21:03:04Z2023-07https://hdl.handle.net/10901/27875La nefritis lúpica (NL) es la complicación más frecuente y grave del Lupus Eritematoso Sistémico (LES), evoluciona a enfermedad renal terminal en aproximadamente 10 % de los pacientes, siendo uno de los principales determinantes de la clasificación histológica. La biopsia es el patrón oro para el diagnóstico, no obstante, dadas las limitaciones, se estudian marcadores otros séricos y urinarios que pueden realizar un abordaje menos invasivo. Objetivo: Analizar la relación entre el grado de proteinuria y sedimento urinario activo con enfermedad proliferativa y exacerbación en pacientes con nefritis lúpica de un centro de referencia del caribe colombiano entre enero 2013 y diciembre 2022. Metodología: Se presenta un estudio retrospectivo, basado en el análisis de las características clínicas, parámetros bioquímicos y urinarios de pacientes con NL del programa de LES en una Clínica de Barranquilla. Se realizó una prueba de normalidad, a las variables continuas se les hicieron estadísticas descriptivas y las cualitativas se representaron en frecuencias absolutas y porcentaje. Se realizó una regresión logística para cálculo de OR, la significancia fue de p < 0.05. Resultados: En este estudio se evaluaron 96 participantes. Al comparar las clases histopatológicas, se encontró una relación positiva de los subtipos proliferativos con mayor grado de proteinuria, sedimento urinario activo, mayor puntuación del SLEDAI-2K, elevación de creatinina y el índice de cronicidad, no se estableció una relación estadísticamente significativa entre un sedimento urinario activo o la severidad de la proteinuria con riesgo superior de agudización y hospitalización. Por su parte, se anticipa que, por cada unidad de aumento en la creatinina, los pacientes tienen 2.25 veces más probabilidades de ser hospitalizados. Conclusión: Estos hallazgos indican que la presencia de proteinuria y sedimento urinario activo es superior en pacientes con subtipos proliferativos de enfermedad, sin embargo, no se relacionan con mayor riesgo de hospitalización. Por otro lado, la elevación de los niveles de creatinina sérica resultó ser una variable que se relaciona con una mayor frecuencia de hospitalización y debe alertar al clínico a un cambio en el abordaje terapéutico para prevenir resultados clínicos desfavorables.Universidad Libre Seccional Barranquilla -- Facultad de Ciencias de la Salud -- Especialización en Medicina InternaLupus nephritis (LN) is the most frequent and serious complication of systemic lupus erythematosus (SLE), progressing to end-stage renal disease in approximately 10% of patients, with histological classification being a major determinant. Biopsy serves as the gold standard for diagnosis; however, due to limitations, other serum and urinary markers are being studied to facilitate a less invasive approach. Objective: To analyze the relationship between the degree of proteinuria and active urinary sediment with proliferative disease and exacerbation in patients with lupus nephritis from a reference center in the Colombian Caribbean region between January 2013 and December 2022. Methodology: A retrospective study is presented, based on the analysis of clinical characteristics, biochemical, and urinary parameters of LN patients from the SLE program at a clinic in Barranquilla. A normality test was conducted, continuous variables were subjected to descriptive statistics, and qualitative variables were represented in absolute frequencies and percentages. Logistic regression was performed to calculate odds ratios (OR), with significance set at p < 0.05. Results: This study evaluated 96 participants. When comparing histopathological classes, a positive relationship was found between proliferative subtypes and higher degrees of proteinuria, active urinary sediment, higher SLEDAI-2K scores, elevated creatinine, and the index of chronicity. However, no statistically significant relationship was established between active urinary sediment or proteinuria severity and increased risk of exacerbation and hospitalization. On the other hand, it was determined that for each unit increase in creatinine, patients had 2.25 times higher odds of being hospitalized. Conclusion: These findings indicate that the presence of proteinuria and active urinary sediment is higher in patients with proliferative disease subtypes; however, they are not associated with an increased risk of hospitalization. Conversely, elevated levels of serum creatinine were found to be a variable associated with a higher frequency of hospitalization, alerting clinicians to consider a change in therapeutic approach to prevent unfavorable clinical outcomes.PDFNefritis lúpicaSedimento UrinarioProteinuriaCreatininaHospitalizaciónLupus nephritisUrinary sedimentProteinuriaCreatinineHospitalizationNefritis lúpicaProteinuriaEnfermedades renalesLupus eritematoso sistémicoRelación entre grado de proteinuria y sedimento urinario activo con clasificación histopatológica y hospitalización en los pacientes con nefritis lúpica de un centro de referencia del Caribe colombiano entre enero 2013 y diciembre 2022Tesis de Especializacióninfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1fMurimi-Worstell IB, Lin DH, Kan H, Tierce J, Wang X, Nab H, et al. Healthcare Utilization and Costs of Systemic Lupus Erythematosus by Disease Severity in the United States. J Rheumatol [Internet]. 2021 Mar;48(3):385–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32611669Singh S, Saxena R. Lupus nephritis. Am J Med Sci [Internet]. 2009 Jun;337(6):451–60. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/19390431Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev. 2010 Mar;9(5): A277-87Calixto O-J, Vargas-Zambrano J-C, Franco J-S, Molano-Gonzalez N, Salazar J-C, Rodríguez-Jiménez M, et al. El costo de la atención ambulatoria del lupus eritematoso sistémico en Colombia. Contrastes y comparaciones con otras poblaciones. 2015;1–66. Available from: http://repository.urosario.edu.co/handle/10336/10533Ruiz-Irastorza G, Espinosa G, Frutos MA, Jiménez-Alonso J, Praga M, Pallarés L, et al. Diagnosis and treatment of Lupus nephritis: Consensus document from the systemic auto-immune disease group (GEAS) of the Spanish society of internal medicine (SEMI) and the Spanish society of nephrology (S.E.N.). Nefrologia. 2012;32(SUPPL. 1):1–45Torres-bustamante M, Suárez DP-, Celis AM, Nuñez SF, Hernández-sierra A. Caracterización clínica de pacientes con nefropatía lúpica en Santander, la importancia de la biopsia renal Clinical and epidemiological characterization of patients with lupus nephropathy in Santander, Colombia: the importance of the renal biopsy. 2019;6(2):122–9Contreras G, Pardo V, Cely C, Borja E, Hurtado A, De La Cuesta C, et al. Factors associated with poor outcomes in patients with lupus nephritis. Lupus [Internet]. 2005;14(11):890–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16335581Rovin BH, Zhang X. Biomarkers for lupus nephritis: the quest continues. Clin J Am Soc Nephrol [Internet]. 2009 Nov;4(11):1858–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19729426Perazella MA. The urine sediment as a biomarker of kidney disease. Am J Kidney Dis [Internet]. 2015 Nov;66(5):748–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25943719Avihingsanon Y, Phumesin P, Benjachat T, Akkasilpa S, Kittikowit V, Praditpornsilpa K, et al. Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int [Internet]. 2006 Feb;69(4):747–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16518330El-Shehaby A, Darweesh H, El-Khatib M, Momtaz M, Marzouk S, ElShaarawy N, et al. Correlations of urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and IL-8 with lupus nephritis. J Clin Immunol [Internet]. 2011 Oct;31(5):848–56. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21691937Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol [Internet]. 2018 Jan 26;3(19). Available from: http://www.ncbi.nlm.nih.gov/pubmed/29374079Zickert A, Sundelin B, Svenungsson E, Gunnarsson I. Role of early repeated renal biopsies in lupus nephritis. Lupus Sci Med. 2014;1(1): e000018Malvar A, Pirruccio P, Alberton V, Lococo B, Recalde C, et al. Histologic versus clinical remission in proliferative lupus nephritis. Nephrol Dial Transplant. 2017 Ago 1;32(8):1338-1344Kim SJ, Lee K, Diamond B. Follicular Helper T Cells in Systemic Lupus Erythematosus. Front Immunol [Internet]. 2018; 9:1793. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30123218Zharkova O, Celhar T, Cravens PD, Satterthwaite AB, Fairhurst A-M, Davis LS. Pathways leading to an immunological disease: systemic lupus erythematosus. Rheumatology (Oxford) [Internet]. 2017;56(suppl_1):i55–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28375453Stojan G, Petri M. Epidemiology of systemic lupus erythematosus: an update. Curr Opin Rheumatol [Internet]. 2018 Mar;30(2):144–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29251660Feldman CH, Hiraki LT, Liu J, Fischer MA, Solomon DH, Alarcón GS, et al. Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000-2004. Arthritis Rheum. 2013 Mar;65(3):753–63Jakes RW, Bae S-C, Louthrenoo W, Mok C-C, Navarra S V, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken) [Internet]. 2012 Feb;64(2):159–68. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22052624Seligman VA, Lum RF, Olson JL, Li H, Criswell LA. Demographic differences in the development of lupus nephritis: A retrospective analysis. Am J Med. 2002;112:726–9Díaz-Coronado JC, Rojas-Villarraga A, Hernandez-Parra D, BetancurVásquez L, Lacouture-Fierro J, Gonzalez-Hurtado D, et al. Clinical and sociodemographic factors associated with lupus nephritis in Colombian patients: A cross-sectional study. Reumatol Clin. 2021;17(6):351–6Kuo C-F, Grainge MJ, Valdes AM, See L-C, Luo S-F, Yu K-H, et al. Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families. JAMA Intern Med [Internet]. 2015 Sep;175(9):1518–26. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26193127Imgenberg-Kreuz J, Carlsson Almlöf J, Leonard D, Alexsson A, Nordmark G, Eloranta M-L, et al. DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus. Ann Rheum Dis [Internet]. 2018 May;77(5):736–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29437559Deng Y, Tsao BP. Updates in Lupus Genetics. Curr Rheumatol Rep. 2017 Nov;19(11):68Lyn-Cook BD, Xie C, Oates J, Treadwell E, Word B, Hammons G, et al. Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol [Internet]. 2014 Sep;61(1):38–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24865418Rother N, van der Vlag J. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Front Immunol [Internet]. 2015;6:610. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26648939Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J, Edens M, et al. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell [Internet]. 2016 Apr 21;165(3):551–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27040498Vinay K, MD A. Patología estructural funcional. 2018Yu ASL, Chertow GM, Luyckx VA, Marsden PA, Skorecki K, Taal MW, et al. EL RIÑÓN. ultima edWeening JJ, D’Agati VD, Schwartz MM, Seshan S V, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int [Internet]. 2004 Feb;65(2):521–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14717922Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018;93(4):789–96Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost [Internet]. 2006 Feb;4(2):295–306. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16420554Schwartz MM, Lan SP, Bernstein J, Hill GS, Holley K, Lewis EJ. Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis [Internet]. 1993 Apr;21(4):374–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8465815Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) [Internet]. 2012 Jun;64(6):797–808. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22556106Gasparotto M, Gatto M, Binda V, Doria A, Moroni G. Lupus nephritis: clinical presentations and outcomes in the 21st century. Rheumatology [Internet]. 2020 Dec 5;59(Supplement_5):v39–51. Available from: https://academic.oup.com/rheumatology/article/59/Supplement_5/v39/60247 33Hu W, Chen Y, Wang S, Chen H, Liu Z, Zeng C, et al. Clinical-Morphological Features and Outcomes of Lupus Podocytopathy. Clin J Am Soc Nephrol [Internet]. 2016 Apr 7;11(4):585–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26983707Anders H-J, Saxena R, Zhao M-H, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Prim [Internet]. 2020 Jan 23;6(1):7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31974366Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med [Internet]. 2008 Feb 28;358(9):929–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18305268Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Sep;71(9):1400–12Appel GB, Cohen DJ, Pirani CL, Meltzer JI, Estes D. Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization. Am J Med [Internet]. 1987 Nov;83(5):877–85. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3674094Waldman M, Madaio MP. Pathogenic autoantibodies in lupus nephritis. Lupus [Internet]. 2005 Jan 2;14(1):19–24. Available from: http://journals.sagepub.com/doi/10.1191/0961203305lu2054oaKavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med [Internet]. 2000 Jan;124(1):71–81. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10629135Martínez-Martínez MU, Llamazares-Azuara LM de G, Martínez-Galla D, Mandeville PB, Valadez-Castillo F, Román-Acosta S, et al. Urinary sediment suggests lupus nephritis histology. Lupus [Internet]. 2017 May;26(6):580–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27687029Yuan M, Tan Y, Li J, Yu X, Zhang H, Zhao M. Urinary sediments could differentiate endocapillary proliferative lupus nephritis and endocapillary proliferative IgA nephropathy. Int Immunopharmacol [Internet]. 2021 Jan;90:107122. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33199236Bihl GR, Petri M, Fine DM. Kidney biopsy in lupus nephritis: look before you leap. Nephrol Dial Transplant [Internet]. 2006 Jul;21(7):1749–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16632559Aragón CC, Tafúr R-A, Suárez-Avellaneda A, Martínez MT, Salas A de Las, Tobón GJ. Urinary biomarkers in lupus nephritis. J Transl Autoimmun [Internet]. 2020;3:100042. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32743523Reyes-Martínez F, Pérez-Navarro M, Rodríguez-Matías A, Soto-Abraham V, Gutierrez-Reyes G, Medina-Avila Z, et al. Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study. Nefrologia [Internet]. 2018;38(2):152–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28755900Salem MN, Taha HA, Abd El-Fattah El-Feqi M, Eesa NN, Mohamed RA. Urinary TNF-like weak inducer of apoptosis (TWEAK) as a biomarker of lupus nephritis. Z Rheumatol [Internet]. 2018 Feb;77(1):71–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27619369Nalbandian A, Crispín JC, Tsokos GC. Interleukin-17 and systemic lupus erythematosus: current concepts. Clin Exp Immunol [Internet]. 2009 Aug;157(2):209–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19604260Crispín JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol [Internet]. 2008 Dec 15;181(12):8761–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19050297Su H, Lei C-T, Zhang C. Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol [Internet]. 2017;8:405. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28484449Richards HB, Satoh M, Shaw M, Libert C, Poli V, Reeves WH. Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. J Exp Med [Internet]. 1998 Sep 7;188(5):985–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9730900wano M, Dohi K, Hirata E, Kurumatani N, Horii Y, Shiiki H, et al. Urinary levels of IL-6 in patients with active lupus nephritis. Clin Nephrol [Internet]. 1993 Jul;40(1):16–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8358870Stewart AG, Thomas B, Koff J. TGF-β: Master regulator of inflammation and fibrosis. Respirology [Internet]. 2018 Dec;23(12):1096–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30284753Kiani AN, Johnson K, Chen C, Diehl E, Hu H, Vasudevan G, et al. Urine osteoprotegerin and monocyte chemoattractant protein-1 in lupus nephritis. J Rheumatol [Internet]. 2009 Oct;36(10):2224–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19648301Tesch GH. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol [Internet]. 2008 Apr;294(4):F697-701. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18272603Kim MJ, Tam FWK. Urinary monocyte chemoattractant protein-1 in renal disease. Clin Chim Acta [Internet]. 2011 Nov 20;412(23–24):2022–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21851811Gonzalez-Aparicio M, Alfaro C. Influence of Interleukin-8 and Neutrophil Extracellular Trap (NET) Formation in the Tumor Microenvironment: Is There a Pathogenic Role? J Immunol Res [Internet]. 2019;2019:6252138. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31093511Rovin BH, Lu L, Zhang X. A novel interleukin-8 polymorphism is associated with severe systemic lupus erythematosus nephritis. Kidney Int [Internet]. 2002 Jul;62(1):261–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12081586Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis [Internet]. 2008 Sep;52(3):595–605. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18725016Malyszko J, Malyszko JS, Bachorzewska-Gajewska H, Poniatowski B, Dobrzycki S, Mysliwiec M. Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients. Transplant Proc [Internet]. 2009;41(1):158–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19249502Satirapoj B, Kitiyakara C, Leelahavanichkul A, Avihingsanon Y, Supasyndh O. Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis. BMC Nephrol [Internet]. 2017 Aug 4;18(1):263. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28778196Genctoy G, Arikan S. Urinary N-Acetyl-Beta-D Glucosaminidase Activity is Associated with Inflammation and Proteinuria in Diabetic and Non-Diabetic Patients with Different Stages of Chronic Kidney Disease. Turkish Nephrol Dial Transplant [Internet]. 2015 May 18;24(2):166–73. Available from: http://turkjnephrol.org/en/urinary-n-acetyl-beta-d-glucosaminidase-activity-isassociated-with-inflammation-and-proteinuria-in-diabetic-and-non-diabeticpatients-with-different-stages-of-chronic-kidney-disease-135690Erdener D, Aksu K, Biçer I, Doğanavşargil E, Kutay FZ. Urinary N-acetyl-betaD-glucosaminidase (NAG) in lupus nephritis and rheumatoid arthritis. J Clin Lab Anal [Internet]. 2005;19(4):172–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16025478Ward MM. Cardiovascular and cerebrovascular morbidity and mortality among women with end-stage renal disease attributable to lupus nephritis. Am J Kidney Dis. 2000;36:516–25Ward MM. Cardiovascular and cerebrovascular morbidity and mortality among women with end-stage renal disease attributable to lupus nephritis. Am J Kidney Dis [Internet]. 2000 Sep;36(3):516–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10977783Contreras G, Mattiazzi A, Guerra G, Ortega LM, Tozman EC, Li H, et al. Recurrence of lupus nephritis after kidney transplantation. J Am Soc Nephrol [Internet]. 2010 Jul;21(7):1200–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20488956Norby GE, Strøm EH, Midtvedt K, Hartmann A, Gilboe I-M, Leivestad T, et al. Recurrent lupus nephritis after kidney transplantation: a surveillance biopsy study. Ann Rheum Dis [Internet]. 2010 Aug;69(8):1484–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20498208Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF, American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology [Internet]. 2016 Jun;123(6):1386–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26992838Fanouriakis A, Kostopoulou M, Cheema K, Anders H-J, Aringer M, Bajema I, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis [Internet]. 2020 Jun;79(6):713–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32220834Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis [Internet]. 2019 Jun;78(6):736–45. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30926722Ruiz-Irastorza G, Espinosa G, Frutos MA, Jiménez-Alonso J, Praga M, Pallarés L, et al. Diagnóstico y tratamiento de la nefritis lúpica. Nefrologia. 2012Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) [Internet]. 2012 Jun;64(6):797–808. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22556106Grootscholten C, Ligtenberg G, Hagen EC, van den Wall Bake AWL, de GlasVos JW, Bijl M, et al. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int [Internet]. 2006 Aug;70(4):732–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16820790ACCESS Trial Group. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol (Hoboken, NJ) [Internet]. 2014 Nov;66(11):3096–104. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25403681Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido E de R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: The EuroLupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum [Internet]. 2002 Aug;46(8):2121–31. Available from: http://doi.wiley.com/10.1002/art.10461Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med [Internet]. 2001 Aug 21;135(4):248–57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11511139Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol [Internet]. 2009 May;20(5):1103–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19369404Cortés-Hernández J, Torres-Salido MT, Medrano AS, Tarrés MV, Ordi-Ros J. Long-term outcomes--mycophenolate mofetil treatment for lupus nephritis with addition of tacrolimus for resistant cases. Nephrol Dial Transplant [Internet]. 2010 Dec;25(12):3939–48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20538787Rovin BH, Solomons N, Pendergraft WF, Dooley MA, 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 [Internet]. 2019 Jan;95(1):219– 31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30420324Ward M, Tektonidou MG. Belimumab as Add-on Therapy in Lupus Nephritis. N Engl J Med [Internet]. 2020 Sep 17;383(12):1184–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32937052Sahin GM, Sahin S, Kiziltas S, Masatlioglu S, Oguz F, Ergin H. Mycophenolate mofetil versus azathioprine in the maintenance therapy of lupus nephritis. Ren Fail. 2008;30(9):865–9Mart GA, Gonz HJ. Nefritis lúpica. (11Coronado Juan, Rojas Adriana, Hernandez Deicy. Clinical and sociodemographic factors associated whit nephritis in colombian patients: a cross-seccional study. reumatol Clin. 2019: p. 1-6Mendez Tatiana, Posso Ivan, Nieto Ivanna. Utility of anti-C1q and antinucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia. Rev colomb reumatol. 2020; 28 (1): p. 1-7gladelMendez Tatiana, Posso Ivan, Nieto Ivanna. Utility of anti-C1q and antinucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia. Rev colomb reumatol. 2020; 28 (1): p. 1-7Torres-bustamante M, Suárez DP-, Celis AM, Nuñez SF, Hernández-sierra A. Caracterización clínica de pacientes con nefropatía lúpica en Santander, la importancia de la biopsia renal Clinical and epidemiological characterization of patients with lupus nephropathy in Santander, Colombia: the importance of the renal biopsy. 2019;6(2):122–9Pinto LF, Guerra L, González JR, Pérez A, Velásquez CJ, Felipe O, et al. Lupus Eritematoso Sistémico: análisis del comportamiento clínico en una población de Medellín. Rev Col Reum 1997; 4:170-173Martínez-Martínez MU, Llamazares-Azuara LM, Martínez-Galla D, Mandeville PB, Valadez-Castillo F, Román-Acosta S, Borjas-García JA, Abud-Mendoza C. Urinary sediment suggests lupus nephritis histology. Lupus. 2017; 26(6): p. 580-587Velasquez Carlos, Colina Yerlin, Correa Sara. Clinicopathological relationship in colombia patients with lupus nephritis. Rev colomb reumatol. 2017; 24 (4): 211-218Zickert A, Sundelin B, Svenungsson E, Gunnarsson I. Role of early repeated renal biopsies in lupus nephritis. Lupus Sci Med. 2014 Aug 6;1(1):e000018. doi: 10.1136/lupus-2014-000018Malvar A, Pirruccio P, Alberton V, Lococo B, Recalde C, Fazini B, Nagaraja H, Indrakanti D, Rovin BH. Histologic versus clinical remission in proliferative lupus nephritis. 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