哪种肾病可以使用利妥昔单抗治疗？

Kidney diseases such as focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis, and primary membranoproliferative glomerulonephritis can be treated with rituximab.

Rituximab for the treatment of focal segmental glomerulosclerosis

The main form of minimal change disease and focal segmental glomerulosclerosis is the rare podocytosis, clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of initial immunosuppressive therapy in both diseases.

Particularly in adults with minimal change disease or focal segmental glomerulosclerosis, relapse, steroid dependence, or resistance are common, and the need to restart steroids and other immunosuppressants is common. There is an urgent need for effective steroid-sparing therapy and the introduction of less toxic immunosuppressants to reduce adverse side effects, especially in patients with complex disease courses.

(a B-cell-depleting monoclonal antibody) is increasingly used off-label in these conditions, although the level of evidence in adult patients is lower.

Rituximab in the treatment of membranous nephropathy

Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in adults. The identification of the phospholipase A2 receptor (PLA2R) as a target antigen in the majority of patients has dramatically changed the treatment of MN and provided the rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been studied in several studies, including 3 randomized controlled trials in which approximately two-thirds of treated patients achieved complete and partial remission of proteinuria.

Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at intermediate and high risk for worsening renal function.

A study showed that in patients with membranous nephropathy and proteinuria, treated with rituximab, at 24 months, the probabilities of complete remission and complete or partial remission using rituximab were 0.42 and 0.83, respectively, and the probabilities of complete remission and partial remission using the periodic regimen were 0.43 and 0.82, respectively.

Rituximab in the treatment of lupus nephritis

Objective: To evaluate the efficacy and safety of rituximab in patients with lupus nephritis treated concomitantly with mycophenolate mofetil (MMF) and corticosteroids in a randomized, double-blind, placebo-controlled phase III trial.

Methods: Patients with grade III or IV lupus nephritis were randomized 1:1 to receive rituximab (1000 mg) or placebo on days 1, 15, 168, and 182. The primary endpoint was renal response status at week 52.

Results: Peripheral CD19+ B cells were depleted by rituximab in 71 of 72 patients. The overall (complete and partial) renal response rate was 45.8% in the 72 patients who received placebo and 56.9% in the 72 patients who received rituximab. Part of the answer is the main reason for the difference. The primary endpoint (high response rate with rituximab) was not met. Eight placebo-treated patients and no rituximab-treated patients required cyclophosphamide rescue therapy at week 52.

Statistically significant improvements in serum complement C3, C4 and anti-double-stranded DNA (anti-dsDNA) levels were observed in patients treated with rituximab. A greater than median decrease in anti-dsDNA levels was associated with a reduction in proteinuria in both treatment groups. The incidence of serious adverse events, including infections, was similar in both groups. The incidence of neutropenia, leukopenia, and hypotension was higher in the rituximab group.

Conclusions: Rituximab treatment resulted in more responders and greater reductions in anti-dsDNA and C3/C4 levels, and the combination of rituximab with MMF and corticosteroids did not produce any new or unexpected safety signals.

Rituximab in the treatment of membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury caused primarily by subendothelial and mesangial deposition of immunoglobulins or complement factors, followed by inflammation and proliferation, especially of the glomerular basement membrane. Recent classifications of MPGN are based on pathogenesis, dividing MPGN into immunoglobulin-related MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD).

Current guidelines recommend treatment with steroids, cytotoxic drugs, with or without plasma exchange, only in subjects with progressive disease (i.e., nephrotic-range proteinuria and decreased renal function). Rituximab is a chimeric B-cell-depleting anti-CD20 antibody that has emerged over the past decade as a treatment option for patients with primary glomerular diseases, such as minimal change disease, focal segmental glomerulosclerosis, or idiopathic membranous nephropathy.

However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-related and idiopathic MPGN treated with rituximab demonstrated partial and complete responses in the majority of cases.

Summary

Although rituximab can treat kidney disease, not all patients with kidney disease can use rituximab. Patients with kidney disease should go to the nephrology department of the hospital in advance to complete the examination under the guidance of a doctor and consult whether they can be treated with rituximab. Patients are not allowed to use medication privately to avoid improper use of medication and delaying treatment.

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