The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors

Abstract

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading contributor to chronic kidney disease (CKD), and calcineurin inhibitors (CNIs) or monoclonal antibodies are currently the best identified therapy. Meanwhile, some developing countries still use alkylating agents (AA) such as cyclophosphamide (CPA) to treat SRNS due to economic reasons. Objectives: This study aims to determine the employability of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker for monitoring therapy in SRNS children and compare the clinical improvement with those treated with an AA and CNIs. Methods: This was a retrospective cohort study conducted at Hasan Sadikin Hospital, Indonesia. The data was collected from July 2019 to July 2020 from 70 children with FSGS. Clinical signs were evaluated monthly, and serum suPAR level was measured at the third and sixth months following therapy. Two-way repeated measures ANOVA was carried out to compare the differences in suPAR level at baseline with the third and sixth months in SRNS patients who received AA and CNIs. Results: The mean age was nearly similar between the two groups based on the t-test (P = 0.140). Steroid-resistant nephrotic syndrome was more frequent in boys than in girls (P = 0.020), according to the Chi-square test. Baseline serum suPAR level was not significantly different between the two groups. In the third month, the daily urinary protein level was higher in SRNS patients that received the AA compared to the CNIs group (P < 0.001). There was a significant interaction between time and treatment (F(2,138) = 7.203, P = 0.001), with higher suPAR level in SRNS patients that received the AA compared to those administered with CNIs at the 3rd and 6th months, but this difference was not statistically significant (P > 0.05). Conclusions: As a noninvasive tool, suPAR is a promising modality in monitoring SRNS therapy, and CNIs have a tendency to achieve faster remission than the AA.