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Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Use of rituximab (RTX) for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is widely described in children. Clinical evidence in adults is limited. The objective of this study was to determine the treatment outcomes of RTX in adults with FSGS and MCD. METHODS:Ovid MEDLINE, SCOPUS, and Cochrane Database of Systematic Reviews were searched up to September 2019. Out of 699 studies, we included 16 studies describing the treatment outcomes of rituximab in adult patients with FSGS or MCD. Results were reported in remission rate and relapse rate. Serious adverse events were also reported. RESULTS:A total of 16 studies were included in our review and analysis. All studies were observational studies and included a total of 221 patients (23.1% FSGS, 76.9% MCD). Mean follow-up duration was 26.3?±?12.8?months. From the analysis of five studies with FSGS patients (n?=?51), the overall remission rate and relapse rate of RTX therapy was 53.6% (95% CI, 15.8-87.6%) and 47.3% (95% CI, 25.4-70.2%), respectively. Complete remission occurred in 42.9%. In contrast, from the analysis of 11 studies with MCD patients (n?=?170), the overall remission rate and relapse rate of RTX therapy was 80.3% (95% CI, 68.5-88.5%) and 35.9% (95% CI, 25.1-48.4), respectively. Complete remission occurred in 74.7%. Subgroup analyses showed that overall remission and relapse were not different after adjusted for study year and RTX dose for both FSGS and MCD. Incidence of serious adverse events was 0.092 events/year. CONCLUSIONS:Rituximab may be considered as an additional treatment to the standard therapy for adult patients with FSGS and MCD. Remissions and relapses are similar between FSGS and MCD. Serious adverse effects of rituximab were uncommon. We encourage further randomized controlled trials to confirm the efficacy of rituximab therapy in these patients.

SUBMITTER: Hansrivijit P

PROVIDER: S-EPMC7160971 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis.

Hansrivijit Panupong P Cheungpasitporn Wisit W Thongprayoon Charat C Ghahramani Nasrollah N

BMC nephrology 20200415 1

<h4>Background</h4>Use of rituximab (RTX) for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is widely described in children. Clinical evidence in adults is limited. The objective of this study was to determine the treatment outcomes of RTX in adults with FSGS and MCD.<h4>Methods</h4>Ovid MEDLINE, SCOPUS, and Cochrane Database of Systematic Reviews were searched up to September 2019. Out of 699 studies, we included 16 studies describing the treatment outcomes of ritux ...[more]

PMID: 32293308

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Project description:BackgroundFocal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results.AimTo assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy.MethodsThis meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included 'FSGS,' 'steroid-resistant nephrotic syndrome', 'rituximab,' and 'plasmapheresis,'. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case-control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model.ResultsEleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I 2 = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I 2 = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival.ConclusionOverall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.

Project description:Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g, glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g, to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

Dataset Information

Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis.

Publications

Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis.

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