Peripheral B-cell depletion did not track neatly with renal recovery
A pediatric nephrology case from Jiangxi Provincial Children’s Hospital describes a girl with secondary steroid-resistant nephrotic syndrome in whom peripheral CD19-positive B-cell counts fell sharply after rituximab, yet heavy proteinuria persisted. Renal remission emerged later during a telitacicept-containing regimen, creating a clear temporal split between measured B-cell pharmacodynamics and the kidney outcome.
The child’s course began in 2017, when she presented at 4 years of age with edema, oliguria, hypoalbuminemia, and heavy proteinuria. Urinary protein became negative after 1 week of full-dose prednisone, establishing a steroid-sensitive pattern at onset. Over the next several years, however, she relapsed roughly four to five times per year, usually during infections or steroid tapering, and eventually entered the familiar but difficult territory of frequently relapsing/steroid-dependent nephrotic syndrome. Tacrolimus and later mycophenolate mofetil each provided only short-lived benefit. The clinical burden was cumulative, and by 2024 the disease had become harder to control despite standard immunosuppression.
Biopsy findings supported minimal change disease, with early focal sclerosis not fully excluded
Kidney biopsy in May 2021 showed 39 glomeruli on light microscopy without global or segmental sclerosis. Immunofluorescence was limited by the amount of tissue, but electron microscopy demonstrated diffuse foot-process effacement and microvillous transformation without electron-dense deposits. The pathology supported minimal change disease, while leaving open the possibility of unsampled early focal segmental glomerulosclerosis. In practical terms, the biopsy fit a podocytopathy rather than an immune-complex glomerulonephritis, which matters because proteinuric relapses in this setting often track with immune dysregulation rather than structural scarring alone.
A relapse in August 2024 brought the case into more difficult territory. After a gastrointestinal infection, the child had marked generalized edema, serum albumin of 6.33 g/L, and 24-hour urinary protein excretion of 5.37 g/day. After infection control, heavy proteinuria persisted. Prednisone was increased to 50 mg/day and tacrolimus to 1 mg every 12 hours, with a trough concentration of 6.67 ng/mL. Four weeks later, proteinuria had improved only partially, to about 2.91 g/day. Because she had previously responded to steroids, this pattern met criteria for secondary steroid-resistant nephrotic syndrome rather than primary resistance.
Rituximab drove CD19 suppression, but remission lagged behind
Rituximab was introduced in two infusions of 340 mg, equivalent to 375 mg/m², given 49 days apart. Screening for hepatitis B, hepatitis C, HIV, tuberculosis, Epstein–Barr virus, and cytomegalovirus was negative, and trimethoprim–sulfamethoxazole was used for prophylaxis. The last pre-treatment CD19-positive B-cell count was 99.78 cells/μL. Thirteen days after the first infusion, the count had dropped to 1.63 cells/μL, then rose again to 10.43 cells/μL immediately before the second infusion. After the second dose, it fell once more to 1.29 cells/μL.
The biology looked convincing on paper, yet the kidney remained stubborn. Twenty-four-hour urinary protein fluctuated between 1.66 and 4.36 g/day, and complete remission was not achieved after rituximab. A single late laboratory point showed serum rituximab of 0.01 μg/mL and a negative anti-rituximab antibody result, but that measurement came too late to reconstruct early exposure, drug clearance, or urinary loss. Heavy proteinuria can alter monoclonal antibody kinetics, and the case leaves open the possibility of suboptimal effective exposure despite apparently profound peripheral B-cell depletion.
This is the central bedside lesson from the case: circulating CD19 suppression did not equal renal remission.
Telitacicept was followed by remission, but causality cannot be assigned
Because proteinuria persisted and the family did not want another rituximab dose, telitacicept 80 mg once weekly was added on December 11, 2024, while prednisone and tacrolimus continued. The dose was selected with reference to age, body weight, and available pediatric experience. Proteinuria fluctuated early in treatment, and by February 1, peripheral CD19-positive B cells had reconstituted to 32.85 cells/μL before remission was documented. On March 12, urine protein first turned negative, and 24-hour urinary protein had fallen to 0.10 g/day. That occurred 132 days after the second rituximab infusion and 91 days after telitacicept was started.
Telitacicept targets BAFF and APRIL, two survival signals that support B-cell maturation and plasma-cell persistence. In a child whose disease had already shown dependence on repeated immunosuppression, dual pathway blockade offers a biologically plausible way to blunt the humoral drive that may sustain podocyte injury even after CD20-positive cells are depleted. Still, the sequence of events does not prove telitacicept caused remission. The long gap between rituximab doses, uncertain early rituximab exposure, ongoing prednisone and tacrolimus, and the natural waxing and waning of nephrotic syndrome all confound attribution. The case therefore supports hypothesis generation, not therapeutic proof.
Sustained remission after stopping telitacicept does not remove the uncertainty
By May 16, 2025, telitacicept was discontinued because of financial pressure. Remission held after discontinuation. During a respiratory tract infection later in the year, urinary protein rose transiently to 2+ on dipstick but fell again without restarting telitacicept, and final follow-up still showed 0.10 g/day of urinary protein. No serious treatment-related reactions were observed.
The safety signal here is reassuring, but the more important scientific point is narrower. Peripheral blood B-cell kinetics alone were not enough to predict the renal course, and a late single rituximab level could not establish whether the antibody exposure was adequate during the period of active disease. For clinicians managing complicated childhood nephrotic syndrome, the case argues for more granular measurement of circulating and tissue B-cell behavior, rituximab pharmacokinetics, and the timing of sequential CD20 plus BAFF/APRIL blockade.
The report does not establish biological rituximab resistance, and it does not isolate telitacicept as the decisive agent. What it does show, with unusual clarity, is a child whose renal remission arrived after the peripheral B-cell readout had already lost its predictive simplicity.