A CASE SERIES OF TELITACICEPT TREATMENT IN CHRONIC KIDNEY DISEASE WITHOUT RENAL BIOPSY

Due to social, religious, and physical constraints, numerous chronic kidney disease (CKD) patients cannot undergo renal biopsy, creating an urgent clinical need. This study aims to preliminarily explore the therapeutic potential of the novel biologic agent telitacicept for CKD patients who refuse or are unable to undergo renal biopsy, focusing on its efficacy and safety.

A retrospective analysis was conducted on two CKD patients treated at our institution. One patient presented with proteinuria and renal insufficiency, negative rheumatic disease antibodies and lupus anticoagulant tests, and no history of diabetes or hypertension. Due to personal religious beliefs, this patient refused both renal biopsy and hormone therapy, resulting in persistent disease activity. The second patient was transferred from another hospital and refused a renal biopsy due to personal religious beliefs. Clinical manifestations included proteinuria and hematuria. The patient had a history of corticosteroid therapy but now refused corticosteroid treatment, with IgA nephropathy not ruled out. Given the active disease and treatment needs of both patients, and in the absence of a pathological diagnosis, based on clinical experience and after fully informing the patients about the treatment plan, potential benefits, and risks, and obtaining their informed consent, a novel biologic agent—telitacicept (240mg, subcutaneous injection, once weekly)—was initiated for both. Systematic long-term follow-up was conducted to evaluate efficacy and safety.

Both patients in this study exhibited marked clinical improvement following treatment with telitacicept. The first patient received full-dose telitacicept (240 mg, subcutaneous, weekly). After 3 months of therapy, the 24-hour urinary protein level decreased from 1.7 g to 0.27 g. Following 6 months of full-dose treatment, the dosage was reduced to 80 mg weekly for maintenance. During the maintenance phase, urinary protein levels remained stable within the range of 0.3–0.5 g. After more than one year of total therapy, the patient’s clinical symptoms continued to improve, renal function remained stable (creatinine levels fluctuated between 60-70 μmol/L, with an estimated glomerular filtration rate (eGFR) around 100 ml/min/1.73 m²), and the patient is currently under observation off therapy. The second patient was treated with full-dose telitacicept (240 mg, subcutaneous, weekly). After more than 2 months of therapy, the 24-hour urinary protein decreased from 1.25 g to 0.35 g, accompanied by a noticeable improvement in clinical symptoms. Renal function remained stable, with serum creatinine around 100 μmol/L and eGFR approximately 70 mL/min/1.73 m². The patient continues to receive full-dose telitacicept and remains under regular follow-up. No significant adverse events were observed in either case, indicating that telitacicept was well tolerated and exhibited a favourable safety profile in this patient population.

Both patients in this report declined a renal biopsy due to religious beliefs. In the absence of pathological confirmation, treatment with telitacicept achieved remarkable clinical improvement, including a marked reduction in proteinuria, sustained disease stabilisation, and good overall safety. These findings highlight telitacicept as a potentially valuable therapeutic option for CKD patients who are unable or unwilling to undergo renal biopsy, providing a practical solution for this unique clinical challenge. Based on these findings and its mechanism of action, it is preliminarily proposed that telitacicept may be suitable for chronic kidney disease patients exhibiting the following clinical characteristics:(1) exclusion of lupus nephritis, anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, or other antibody-mediated glomerulopathies, with negative anti-phospholipase A2 receptor (PLA2R) antibody tests ruling out membranous nephropathy;(2) absence of typical secondary causes such as diabetic nephropathy or hypertensive renal damage; and (3) clinical manifestations of significant proteinuria (≥1 g/24 h), with or without hematuria. If a patient presents with extremely severe proteinuria or rapidly progressive disease reaching a critical stage that necessitates immediate initiation of high-dose corticosteroids or intensive immunosuppressive therapy. For patients meeting these criteria, their disease type is likely attributable to conditions associated with telitacicept's target pathways. When renal biopsy—the pathological “gold standard”—is not feasible, telitacicept may serve as a therapeutic option, directly intervening in the underlying common immune pathogenesis. In the present study, Case 1 demonstrated successful dose tapering and eventual discontinuation of therapy with sustained remission, while Case 2 showed a rapid and substantial clinical response within two months of treatment. These outcomes further support the therapeutic potential of telitacicept in this patient population. In summary, this study preliminarily suggests that telitacicept offers an innovative preferred treatment option for specific types of chronic kidney disease patients, demonstrating significant clinical translational value. Its broad application prospects warrant validation through larger-scale prospective studies.