A case of IgA nephropathy presenting with nephrotic syndrome and poor response to steroid therapy treated with telitacicept

IgA nephropathy (IgAN) is a syndrome characterized by diverse clinical and pathological manifestations and marked heterogeneity, representing the most common form of primary glomerular disease. Its pathogenesis is complex, conventional treatment options are limited, and specific therapeutic approaches are lacking, resulting in an overall poor prognosis. The 2024 KDIGO draft guideline highlights that reducing proteinuria to 0.5 g/day or even below 0.3 g/day serves as a surrogate marker for improved renal outcomes in IgAN. Management of IgAN should integrate three key aspects: symptomatic treatment, targeting underlying causes, and anti-inflammatory therapy. While glucocorticoids demonstrate some efficacy in treating IgAN, a careful balance between therapeutic benefits and potential side effects must be assessed prior to their use.

BLyS and APRIL are key cytokines involved in the pathogenesis of IgA nephropathy. Telitacicept exerts dual inhibition by simultaneously targeting both BLyS and APRIL, thereby providing improved control of disease activity. Results from a domestic multicenter Phase II clinical trial of telitacicept in patients with IgA nephropathy demonstrated that telitacicept significantly improved urine protein levels and estimated glomerular filtration rate (eGFR), while markedly reducing serum levels of IgA, IgG, and IgM. The incidence of adverse events in the telitacicept group was comparable to that in the placebo group, with all events being mild to moderate in severity and no severe adverse events reported. However, the efficacy of telitacicept in treating IgA nephropathy presenting with nephrotic syndrome remains inconclusive.

This case involves a 36-year-old young to middle-aged female who was admitted with the chief complaint of bilateral lower limb edema for 4 months, which had worsened over the past week. Following a series of laboratory tests, she was diagnosed with nephrotic syndrome and moderate to severe mesangial proliferative IgA nephropathy (M1 E1 S1 T0 C0; see Figure 1 for details). She received treatment with dapagliflozin, hydroxychloroquine, losartan potassium, and prednisone for 6 months. Although her urinary protein level decreased significantly compared to pre-treatment levels, it remained elevated, ranging from 4.28 to 5.25 g/d. Concurrently, the patient experienced substantial weight gain, with a body mass index (BMI) of 35.16 kg/m². As the initial treatment regimen only achieved partial remission and the patient developed severe obesity, significantly impairing her work and quality of life, the therapeutic strategy was modified. Corticosteroids were rapidly tapered, and subcutaneous telitacicept at a dose of 160 mg once weekly was initiated in June 2022.

After one month of treatment, the patient's proteinuria showed improvement. By six months, urinary protein had decreased to less than 1.5 g/day. After adjusting the dosage to 80 mg once weekly for an additional three months, urinary protein was further reduced to below 1.0 g/day, demonstrating a more pronounced reduction in proteinuria. Telitacicept was then gradually tapered to 80 mg every other week and subsequently to once-monthly subcutaneous injections. Over the following six months, the patient's urinary protein consistently remained below 0.3 g/day, achieving complete remission (see Table 1 and Figure 2 for details). The total duration of telitacicept treatment was 19 months (from June 2022 to January 2024), and no adverse effects were observed during its administration.The most recent follow-up on May 3, 2025, revealed an albumin level of 48.2 g/L, urinary protein of 0.21 g/day, creatinine of 63 μmol/L, and a BMI of 21.48 kg/m². The patient has remained off telitacicept for 16 months, with no recurrence of the disease.

In this case, Telitacicept demonstrated efficacy in treating IgA nephropathy presenting with nephrotic syndrome and showing a suboptimal response to corticosteroid therapy, with few side effects and a favorable safety profile. No relapse was observed after drug discontinuation. A Phase III clinical study of Telitacicept for IgA nephropathy is currently underway, which may usher in a new era of targeted biologic therapy for IgA nephropathy.