Background: Recurrent focal segmental glomerulosclerosis (rFSGS) is a significant cause of graft failure in pediatric kidney recipients. Low-density lipoprotein apheresis (LDL-A) is an FDA-approved treatment for pediatric FSGS with unclear efficacy. This meta-analysis aimed to determine the efficacy of LDL-A in pediatric rFSGS.
Methods: After registration in PROSPERO (ID CRD42024544869), 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. Case reports, case series, randomized controlled trials, non-randomized controlled trials, and observational studies (cross-sectional, case-control, or cohort studies) that reported remissions and urine protein creatinine (UPC) ratio for patients <18 years old diagnosed with rFSGS post-kidney transplant treated with LDL-A were included. Non-English articles were excluded.

Seven studies met the inclusion criteria describing 24 patients who received LDL-A for rFSGS. Each study was assessed for selection bias, attrition bias, reporting bias, publication bias, and funding conflicts. Patient remission was determined by urine protein creatinine (UPC) ratio at the latest follow-up date. Complete, partial and no remission were defined as a UPC ratio of less than 300 mg/g, 300-3500 mg/g, and >3500 mg/g (3.5 g/g) respectively. 
Results: Complete and partial remission were achieved in 46% and 38%, respectively. For patients with a follow-up duration greater than or equal to 6 months, complete and partial remission were achieved in 50% and 44%, respectively. No graft loss was reported. Of the 4 patients that did not achieve remission, 2 had stable graft function 11 months and 4.5 years post-treatment, 1 developed ESRD after 7.8 years, and 1 patient died shortly after treatment due to an unrelated medical condition. 

One study reported no adverse effects associated with LDL-A, and 2 studies reported adverse effects but these were not confirmed to be caused by the LDL-pheresis (BK viremia, neutropenia, retroperitoneal hemorrhage, common femoral vein thrombus, Candida bacteremia, nausea, vomiting, diarrhea, abdominal pain, fever/infection, pharyngitis, headache, lightheadedness, malaise, hypotension, leg cramps, allergic reaction, pneumonia, and anemia). Limitations of our study include that all the included studies have moderate to 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: Overall, 84% of patients had partial or complete remission when their treatment included LDL-A. We aim to assess LDL-A as first-line treatment for rFSGS in pediatric kidney transplant recipients based on observed overall effectiveness in this meta-analysis.