#4663 BLOOD AND URINARY CYTOKINE PROFILES AND CLINICAL OUTCOME IN PRIMARY MEMBRANOUS NEPHROPATHY AND DIABETIC KIDNEY DISEASES

Abstract

Abstract Background and Aims Primary membranous nephropathy (MN) is an autoimmune, immune complex-mediated primary glomerulopathy causing podocyte injury and nephrotic syndrome. The results of therapy may be suboptimal and biomarkers are needed that predict the need for immune suppression and the response to different immunosuppression regimens. Diabetic kidney disease (DKD) is the most common cause of kidney failure. It is characterized by non-immune podocyte injury that may lead to nephrotic syndrome. We evaluated the circulating and urine cytokine pattern and pathophysiologic difference between both conditions. For MN, we further aimed at identifying the biomarkers of immunosuppressive treatment response. Method 192 MN data-points from the STARMEN trial and 92 DKD from the biobank of IIS-FJD-UAM were included. We analyzed the blood and urine samples by HISCL (Sysmex Inc. Kobe, Japan), a chemiluminescence immunoassay that can afford a high-throughput multiplex cytokine analysis. Sixteen biomarkers were measured and evaluated for the correlation with the clinical outcome (eGFR, uPCR, 24-hour proteinuria). Also, the biomarkers’ concentration at baseline was compared with the treatment response during 6-9 months and the disease status after treatment until 24 months. The treatments evaluated STARMEN were Tacrolimus-Rituximab (TacRt) and alternating therapy with corticosteroids-cyclophosphamide. Box plot and Mann Whitney U test were used to assess subgroup differences and Spearman's rank correlation to assess correlation between variables. Results Median age, baseline eGFR and proteinuria for the MN and DKD cohorts were 53 and 66 years, 74 and 52 ml/min/1.73 m2, and 8.8 and 0.2 g/24h, respectively. Five cytokine markers in blood and 5 in urine from MN and 2 in blood and 2 in urine from DKD showed a significant correlation with proteinuria (Table). Circulating TNFa had been previously related to both MN and DKD pathophysiology and we confirmed its correlation with clinical outcomes in both. CCL20 is one of blood biomarkers correlated with anti-PLA2R (rS = 0.151, p = 0.036) and proteinuria in MN but not DKD. We identified a baseline urinary Protein A whose concentration differed between responders and non-responders to TacRt. Conclusion MN and DKD displayed characteristic cytokine patterns. Protein A is related to the progression of chronic inflammation and B cells. Its presence in urine and the differences between TacRt responders and non-responders suggest that high inflammatory progression activities may offset the treatment response. In conclusion, protein A could be the potential prognostic marker of TacRt response. However, additional investigation is needed to confirm and evaluate the possible application to other glomerular diseases.