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This retrospective exploratory study aimed to identify early clinical indicators of kidney prognosis in primary nephrotic syndrome (NS). Univariate Cox proportional hazards regression analysis identified clinical parameters in the 2-month period after initiating immunosuppressive therapy (IST); it predicted 40% reduction in the estimated glomerular filtration rate (eGFR) in 36 patients with primary NS. Time-dependent receiver operating characteristic curve analysis was used to evaluate the performance of the predictors for the cumulative incidence of 40% reduction in the eGFR up to 8 years after initiating IST. The mean follow-up period was 71.9 months. The eGFR was reduced by 40% in four patients. Significant predictors for time to 40% reduction in the eGFR were as follows: an increase in the serum soluble urokinase plasminogen activator receptor (s-suPAR) 2 months after initiating IST (Δs-suPAR (2M); hazard ratio (HR) for every 500 pg/mL increase: 1.36, P = 0.006), s-suPAR at 2 months after initiating IST (s-suPAR (2M); HR for every 500 pg/mL increase: 1.13, P = 0.015), urinary protein-to-creatinine ratio (u-PCR) (u-PCR (2M); HR for every 1.0 g/gCr increase: 2.94, P = 0.003), and urinary liver-type fatty acid-binding protein (u-L-FABP) (u-L-FABP (2M); HR for every 1.0 μg/gCr increase: 1.14, P = 0.006). All four factors exhibited high predictive accuracy for cumulative incidence of 40% reduction in the eGFR up to 8 years after initiating IST, with areas under the receiver operating characteristic curve of 0.92 for Δs-suPAR (2M), 0.87 for s-suPAR (2M), 0.93 for u-PCR (2M), and 0.93 for u-L-FABP (2M). These findings suggest that Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) could be useful indicators of initial therapeutic response for predicting kidney prognosis in primary NS. [ABSTRACT FROM AUTHOR]

Background: The non-classical class I molecule human leukocyte antigen-G (HLA-G) has great potential to modulate the immune response. However, the mechanism underlying HLA-G induction remains unknown. Therefore, this study aimed to determine the factors that induce HLA-G expression on proximal tubular epithelial cells (pTECs) in renal transplanted allografts in vivo and in vitro. Methods: This study included 40 adult Japanese patients with renal allografts (35 and five patients with kidneys from living and deceased donors, respectively) who survived for at least 1 year. We evaluated HLA-G1/5 expression using an immunofluorescence method and investigated the induction of HLA-G expression in primary cultured human pTECs by cytokines and immunosuppressants. Results: The HLA-G expression was identified in the perinuclear region or on the basement membrane of pTECs of renal biopsy tissue in 12 (30%) of 40 patients at 2–4 weeks and at 1 year following transplantation. A reduction of 30% in the estimated glomerular filtration rate was lower in the HLA-G-positive group than that of the negative group (p = 0.016). Cox proportional hazard models also demonstrated that HLA-G1/5 expression on pTECs was an independent predictor of improved renal allograft function (hazard ratio, 0.189; 95% CI 0.041–0.850, p = 0.030). Interferon-beta was the most powerful inducer of HLA-G expression in vitro, whereas the immunosuppressants everolimus, tacrolimus, cyclosporin, and dexamethasone did not induce any expression. Conclusion: Unlike immunosuppressants, acquired HLA-G expression might confer long-term renal preservation effects in renal transplanted allografts. [ABSTRACT FROM AUTHOR]