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Immunoglobulin A nephropathy (IgAN) is a primary glomerulonephritis commonly seen in patients with East Asian and Caucasian ancestry. Renin-angiotensin-aldosterone system (RAAS) inhibition to help with proteinuria reduction to an acceptable range of around 0.5 g/g is the cornerstone of management in IgAN patients. Patients at increased risk of progression of renal dysfunction are treated with immunosuppressive medications with systemic glucocorticoids considered as first-line immunosuppressive agents. Recent research has shown promising results with sparsentan and TRF-budesonide as alternative options instead of traditional RAAS inhibition or systemic glucocorticoids respectively.
We report a case of 21-year-old Caucasian male patient with untreated/partially treated IgAN due to non-compliance with medical care who had further reduction in proteinuria with 4-month therapy of sparsentan and TRF-budesonide compared to traditional RAAS inhibition and maintenance Cellcept. Our patient was diagnosed with IgAN at the age of 17 with renal biopsy notable for IgA nephropathy with no crescent, no chronicity and moderate foot process effacement. At the time of diagnosis, serum creatinine was noted to be 1.31 mg/dL with proteinuria of 0.7 g/g. Though the patient was started on Cellcept for immunosuppression along with Lisinopril for RAAS inhibition he was eventually lost to follow up in the process of extablishing with adult nephrologist and discontinued medications. The patient again presented at the age of 21 with serum creatinine worsened to 2.7-3.0 mg/dL and proteinuria worsened to 4.2 g/g. Repeat renal biopsy was notable for significant segmental and global glomerulosclerosis in 30 out of 38 glomeruli, 1 glomerulus with fibrocellular crescent, mesangial hypercellularity, severe interstitial fibrosis, and tubular atrophy involving approximately 50% of the renal cortex. The patient was treated with a course of high dose steroid with rapid taper with improvement in proteinuria to 400 mg/g. Proteinuria again worsened to 720 mg/g after the completion of steroid taper and on Cellcept and Irbesartan therapy. After discussing various other treatment options with the patient vs continuing him on ongoing management, a mutual decision was made to switch his irbesartan to sparsentan and initiate therapy with TRF-budsonide. Patients' proteinuria improved further to 92 mg/g with 4 months of therapy with these medications. No significant side effects except for acne were noted.
Level of proteinuria reduction is one of the major prognostic factor in patients with IgAN. This serves as a surrogate marker for improved kidney function and outcomes in IgAN patients. Systemic glucocorticoids, though associated with significant proteinuria reduction, are usually rapidly tapered and discontinued to avoid significant systemic toxicity and the patients are eventually continued on traditional RAAS inhibition as well as Cellcept for maintenance in some cases. Our case demonstrates the benefit of further proteinuria reduction with treatment with recently FDA approved medications, sparsentan, a dual endothelin angiotensin receptor antagonist and TRF-budesonide when compared to traditional RAAS inhibition and Cellcept. These newer agents can be considered as treatment options in patients at high risk of disease progression while closely monitoring for side effects.