Telitacicept in the Treatment of Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits (PGNMID): A Prospective, Single-Arm Study

Study Rationale Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare but aggressive renal manifestation of monoclonal gammopathy of renal significance (MGRS). Conventional immunosuppression yields limited and inconsistent responses; no therapy is approved specifically for PGNMID. Pathogenic immunoglobulins are produced by dysregulated B-cell or plasma-cell clones. Telitacicept is a novel TACI-Fc fusion protein that simultaneously neutralizes B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby suppressing both B-cell maturation and plasma-cell survival. This mechanism may interrupt the production of the monoclonal immunoglobulins that drive PGNMID.

Objectives Primary: To determine the change in 24-hour urine protein excretion from baseline to Week 24 after telitacicept therapy.

Secondary: (1) Change in estimated glomerular filtration rate (eGFR); (2) change in urinary red-blood-cell count; (3) change in serum IgG, IgA, IgM, C3, and C4; (4) safety and tolerability.

Study Design Single-center, open-label, investigator-initiated, prospective single-arm trial. Ten adults with biopsy-proven PGNMID will be enrolled. After a 12-week run-in on optimized ACE inhibitor or ARB therapy (to confirm persistent proteinuria ≥1 g/day), participants will receive telitacicept 160 mg subcutaneously once weekly for 24 consecutive weeks. Post-treatment follow-up continues to Week 28.

Population Inclusion: Age ≥18 y; renal biopsy consistent with PGNMID; 24-h proteinuria ≥1 g on two occasions ≥4 weeks apart despite maximal ACEi/ARB; eGFR ≥20 mL/min/1.73 m² (CKD-EPI); willingness to use effective contraception.