Effect of Sequential Targeted-Release Formulation (TRF)-Budesonide and Sparsentan Therapy in a Patient with IgAN: Can Histopathology Predict Therapeutic Response?

Introduction: Background: There are four FDA approved new medications for IgAN within the past few years and more are in the pipeline. The optimal therapeutic approach for an individual patient remains challenging. Despite KDIGO guidelines advising against the sole use of kidney biopsies for guiding treatment decisions, histopathological evaluation may offer valuable insights. We present a case of a patient with IgAN and persistent proteinuria despite maximal supportive care. The patient exhibited no therapeutic response to initial TRF-Budesonide treatment but achieved complete remission following subsequent Sparsentan administration. Case Description: 50 y.o. male diagnosed with IgAN in 2013 with biopsy shown 17% global sclerosis. and 40% IFTA. Oxford classification: M0, E0, S1, T2, C0. He was treated with Losartan 100 mg a day and Lisinopril 20 mg twice a day for many years In 2021, his UPC ratio was 2.4-3 mg/mg. He was started on Empagliflozin in July 2021 and Lisinopril decreased to 20 mg a day. Urine protein-to-creatinine ratio (UPCR) decreased to 0.9 mg/mg one month after the initiation of Empagliflozin. However, it increased back to 2.3 mg/mg soon after. The patient was started on TRF-Budesonide in Feb 2023 during which time his UPCR remained at 2.5-3 mg/mg range. The TRF-Budesonide was tapered off in Dec 2023. He started on Sparsentan in Jan 2024 and UPCR decreased to 1.1 mg/mg within one month. It stayed in this range for 8 months, then down to 0.4 mg/mg since Oct 2024. (figure). Discussion: This case demonstrates that a kidney biopsy could help predict responses to different therapies for IgAN. For biopsies showing higher degree of IF/TA, supportive therapies are more effective than immunotherapies. The new guidelines have distinguished this and can help guide appropriate effective therapies based on histological variables.Improvement of UPCR with supportive therapies