Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes.
Por:
Roca N, Alvaro Madrid Aris, Lopez M, Fraga G, Jatem E, Gonzalez J, Martinez C and Segarra A
Publicada:
1 jul 2021
Ahead of Print:
14 dic 2020
Categoría:
Nephrology
Resumen:
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 (IFN?), 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.
Filiaciones:
Roca N:
Servicio Nefrologia Pediátrica, Hospital Universitari de Vic, Universitat de Vic, Barcelona, Spain
Alvaro Madrid Aris:
Servicio de Nefrología Pediátrica, Hospital de Sant Joan de Déu de Barcelona, Barcelona, Spain
Lopez M:
Servicio de Nefrología Pediátrica, Hospital Vall d'Hebrón, Barcelona, Spain
Fraga G:
Servicio de Nefrología Pediátrica, Hospital Vall d'Hebrón, Barcelona, Spain
Servicio de Nefrología Pediátrica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Jatem E:
Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain
Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain
Gonzalez J:
Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain
Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain
Martinez C:
Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain
Segarra A:
Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain
Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain
Green Published, gold
|