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Primary immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis. IgAN is an autoimmune disorder with decreased O-linked galactosylation of the IgA1 hinge region leading to increased galactose-deficient IgA1 (Gd-IgA1) molecules in the circulation. This leads to the production of autoantibodies against Gd-IgA1, forming circulating immune complexes which deposit in the glomerular mesangium causing renal damage. Patients with primary IgAN who are at low risk for progressive renal dysfunction are managed conservatively with angiotensin inhibition, SGLT2 inhibitors, good blood pressure control and lifestyle changes. Patients at increased risk for progressive renal dysfunction with high oxford classification scores, do require management with immunosuppressive agents. Both sparsentan and targeted-release formulation (TRF) budesonide have been recently granted accelerated FDA approval for management of patients with primary IgAN.
We report a patient with primary IgAN, who was at increased risk of progressive renal dysfunction with good response for both sparsentan and TRF-budesonide as initial therapy. Our patient is a 47-year-old Caucasian male with past history of sub optimally controlled hypertension, well controlled diabetes mellitus on glipizide and morbid obesity, referred to nephrology clinic for proteinuria and hematuria. Initial lab work up with normal serum creatinine, but with significant hematuria (large blood and 32 RBCs) as well as nephrotic range proteinuria (urine protein-creatinine ratio of 7.8 g/g). Serological workup with ANA, ANCA, Hepatitis panel, Rheumatoid factor, HIV panel were negative with normal complement levels. Renal biopsy notable for crescentic IgAN with an oxford classification score of M1E1S0T0C1. Secondary to the patient's significant nephrotic range proteinuria with crescentic IgAN on biopsy and high MESTC score, the patient was offered various options for angiotensin inhibition as well as immunosuppressive therapy. An informed decision was made to start the patient on sparsentan for angiotensin inhibition as well as TRF-budesonide as immunosuppressive agent. Within 2 months of initiation of therapy, patients' proteinuria improved from 7.8 g/g to 1.2 g/g and hematuria improved to moderate blood on dipstick urinalysis and 3 RBCs on microscopy. No significant side effects noted even after 4 months of therapy to date.
Treatment options for IgAN are rapidly evolving. Though supportive therapy is the backbone of treatment for all patients with IgAN, most of these patients also do benefit from simultaneous treatment with other medications depending on histological features on biopsy and other co-existing risk factors. Sparsentan, a selective antagonist of the angiotensin II receptor as well as endothelin 1 receptor, recently received FDA approval for proteinuria reduction in IgAN patients at risk of rapid disease progression. Similarly, TRF-budesonide also did receive FDA approval for immunosuppressive management in IgAN patients with high-risk of progression. This case demonstrates the successful use of these agents as primary treatment options in patients with IgAN with appropriate response in our patient without any untoward side effects. Though long-term safety and efficacy data are currently pending, data so far is promising for the management of IgAN.