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Background Activation of parietal–epithelial cells (PECs) with neo-expression of CD44 has been found to play a relevant role in the development of focal and segmental glomerulosclerosis (FSGS). The aim of this study was to analyse whether the expression of CD44 by PECs in biopsies of minimal change disease (MCD) is associated with the response to corticosteroids, with kidney outcomes and/or can be considered an early sign of FSGS. Methods This multicentric, retrospective study included paediatric and adult patients with MCD. Demographic, clinical and biochemical data were recorded, and biopsies were stained with anti-CD44 antibodies. The association between PECs, CD44 expression and the response to corticosteroids, and kidney outcomes were analysed using logistic, Kaplan–Meier and Cox regression analyses. Results A total of 54 patients were included: 35 (65%) <18 years and 19 (35%) adults. Mean follow-up was 68.3 ± 37.9 months. A total of 19/54 patients (35.2%) showed CD44-positive staining. CD44-positive patients were younger (14.5 ± 5 versus 21.5 ± 13, P = 0.006), and showed a higher incidence of steroid-resistance [11/19 (57.8%) versus 7/35 (20%), P = 0.021; odds ratio: 5.5 (95% confidence interval 1.6–18), P = 0.007] and chronic kidney disease [9/19 (47.3%) versus 6/35 (17.1%), P = 0.021; relative risk: 3.01 (95% confidence interval 1.07–8.5), P = 0.037]. Follow-up re-biopsies of native kidneys (n = 18), identified FSGS lesions in 10/12 (83.3%) of first-biopsy CD44-positive patients versus 1/6 (16.7%) of first-biopsy CD44-negative patients (P = 0.026). Conclusions In patients with a light microscopy pattern of MCD, CD44-positive staining of PECs is associated with a higher prevalence of steroid resistance and worse kidney outcomes, and can be considered an early sign of FSGS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Serum levels of soluble urokinase-type plasminogen activator receptor (suPAR) are high in some patients with idiopathic nephrotic syndrome (INS). Given that suPAR constitutes a predictor of vascular disease and has been associated with endothelial dysfunction, we hypothesized that suPAR levels are related to endothelial activation or dysfunction in INS patients. The aims of this study were to evaluate the relationship between serum concentrations of endothelial biomarkers and suPAR in patients with different histological patterns of INS and healthy controls, and to determine the demographic, clinical and biochemical characteristics of INS patients that influence suPAR serum levels. Methods This observational, cross-sectional study included patients with INS, diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN) by renal biopsy. Patient demographic, clinical and biochemical characteristics were recorded and blood samples were obtained at the time of diagnosis. Measurements of suPAR and endothelial molecules via serum levels were performed using Enzyme-Linked ImmunoSorbent Assay kits. Results Patients with nephrotic syndrome (n  = 152) caused by FSGS, MCD or MN had increased circulating levels of endothelial markers. suPAR levels positively correlated with age and the serum levels of almost all endothelial markers. Generally, endothelial cell molecules positively correlated with each other. suPAR levels were not associated with the histopathological pattern of INS. Conclusions In patients with INS secondary to FSGS, MCD and NM, circulating levels of suPAR are independent of the primary renal disease, and significantly associated with age, glomerular filtration rate and the levels of various endothelial markers. [ABSTRACT FROM AUTHOR]