1. Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
- Author
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Gloria Fraga, Jorge González, Neus Roca, A. Madrid, Elias Jatem, Cristina Martínez, Mercedes López, Alfons Segarra, Institut Català de la Salut, [Roca N] Servicio Nefrologia Pediátrica, Hospital Universitari de Vic, Universitat de Vic, Barcelona, Spain. [Madrid A] Servicio de Nefrología Pediátrica, Hospital de Sant Joan de Déu de Barcelona, Barcelona, Spain. [Lopez M] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Fraga G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Servicio de Nefrología Pediátrica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Jatem E, Gonzalez J] Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain. Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Endotype ,030232 urology & nephrology ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Gastroenterology ,0302 clinical medicine ,Focal segmental glomerulosclerosis ,Other subheadings::/therapeutic use [Other subheadings] ,030212 general & internal medicine ,Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Adrenal Cortex Hormones [CHEMICALS AND DRUGS] ,Proteinuria ,medicine.diagnostic_test ,biology ,Haptoglobin ,inflammatory response ,endotypes ,Nephrology ,idiopathic nephrotic syndrome ,Renal biopsy ,medicine.symptom ,Glomerulosclerosi - Tractament ,medicine.medical_specialty ,Corticosteroides - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Renal function ,03 medical and health sciences ,Cluster analysis ,Idiopathic nephrotic syndrome ,Internal medicine ,Biopsy ,medicine ,hormonas, sustitutos de hormonas y antagonistas de hormonas::hormonas::hormonas de la corteza suprarrenal [COMPUESTOS QUÍMICOS Y DROGAS] ,AcademicSubjects/MED00340 ,enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::nefritis::glomerulonefritis::glomeruloesclerosis focal [ENFERMEDADES] ,Lymphocyte populations ,focal segmental glomerulosclerosis ,Transplantation ,Otros calificadores::/uso terapéutico [Otros calificadores] ,lymphocyte populations ,business.industry ,Interleukins ,Endotypes ,Inflammatory response ,Original Articles ,medicine.disease ,interleukins ,SuPAR ,Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Nephritis::Glomerulonephritis::Glomerulosclerosis, Focal Segmental [DISEASES] ,biology.protein ,business ,cluster analysis - Abstract
Objectives Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids., Graphical Abstract
- Published
- 2020
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