Low-density lipoprotein apheresis for recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: a systematic review and meta-analysis.

backgroundRecurrent focal segmental glomerulosclerosis (rFSGS) is a significant cause of graft failure in pediatric patients. Low-density lipoprotein apheresis (LDL-A) is an FDA-approved treatment for pediatric FSGS, but its efficacy is unclear.

objectivesThis systematic review and descriptive meta-analysis aimed to determine the efficacy of LDL-A in pediatric kidney transplant recipients with rFSGS. DATA SOURCES: We performed a comprehensive search in Ovid MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase (Elsevier), CINAHL (EBSCO), and Scopus (Elsevier) on May 14th, 2024. STUDY ELIGIBILITY CRITERIA: Studies deemed eligible to be included were case reports, case series, randomized controlled trials, non-randomized controlled trials, and observational studies that reported patient-level data for subjects less than 18 years old who were administered any protocol of LDL-A following FSGS recurrence post-kidney transplant, and that provided remission status and urine protein-creatinine ratio (UPCR) ranges or values from at least one follow-up after LDL-A initiation. PARTICIPANTS AND

interventionsFrom the 8 studies that met the inclusion criteria, there were 25 patients who received LDL-A following rFSGS diagnosis post-transplant who were included for meta-analysis. STUDY APPRAISAL AND SYNTHESIS

methodsEach study was assessed for selection bias, attrition bias, reporting bias, publication bias, and funding conflicts. The remission status for each patient was determined by the UPCR measured at the latest follow-up reported. Complete remission was defined as UPCR

resultsThe pooled proportion of patients that achieved complete remission or partial remission was 0.36 (95% confidence interval (CI), 0.13-0.61) and 0.37 (95% CI, 0.14-0.62), respectively, at a median follow-up duration of 8 months (IQR 6-24 months) after LDL-A initiation. Median serum albumin and eGFR values were increased following LDL-A while UPCR decreased, consistent with clinical improvement. No significant differences in remissions were detected between LDL-A protocols, though the detection of real effects may be limited due to small sample sizes and heterogeneity. LIMITATIONS: All the included studies have moderate/high risk of bias due to study type, report type, and sample size. There is substantial variability between LDL-A protocols and previous treatments received by patients, possibly contributing to heterogeneity in outcomes between studies. CONCLUSIONS AND IMPLICATIONS OF KEY

findingsLDL-A achieved a complete remission rate of 36% (95% CI, 0.13-0.61) and a partial remission rate of 37% (95% CI, 0.14-0.62). Despite limited cases, LDL-A may be effective for pediatric rFSGS post-kidney transplant, warranting studies on its early use post-transplant. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (ID CRD42024544869).