Background Recurrent 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. Objectives This 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 interventions From 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 methods Each 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 <InlineEquation ID="IEq1"> <EquationSource Format="TEX">$\le$</EquationSource> <EquationSource Format="MATHML"><math> <mo>≤</mo> </math></EquationSource> </InlineEquation> 0.2 g/g, partial remission as UPCR between 0.2 and 2.0 g/g, and no remission as UPCR <InlineEquation ID="IEq2"> <EquationSource Format="TEX">$\ge$</EquationSource> <EquationSource Format="MATHML"><math> <mo>≥</mo> </math></EquationSource> </InlineEquation> 2.0 g/g. For our main outcome, the proportions of patients that achieved complete or partial remission were determined by study, then pooled estimates of effect size were calculated using a random-effects inverse-variance model. As a secondary outcome, the average effects of LDL-A on measures of kidney function were quantified by determining the median across individual changes in serum albumin, serum creatinine, estimated glomerular filtration rate (eGFR), and UPCR. Finally, subgroup analyses comparing remissions between LDL-A protocols were performed using Fisher’s exact test. Results The 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 findings LDL-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). Graphical abstract

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

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2026年2月11日

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Emily T. Hayes,
Debora Matossian,
Annie B. Wescott,
Priya S. Verghese

摘要

Background

Recurrent 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.

Objectives

This 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 interventions

From 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 methods

Each 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 $\le$ $\leq$ 0.2 g/g, partial remission as UPCR between 0.2 and 2.0 g/g, and no remission as UPCR $\ge$ $\geq$ 2.0 g/g. For our main outcome, the proportions of patients that achieved complete or partial remission were determined by study, then pooled estimates of effect size were calculated using a random-effects inverse-variance model. As a secondary outcome, the average effects of LDL-A on measures of kidney function were quantified by determining the median across individual changes in serum albumin, serum creatinine, estimated glomerular filtration rate (eGFR), and UPCR. Finally, subgroup analyses comparing remissions between LDL-A protocols were performed using Fisher’s exact test.

Results

The 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 findings

LDL-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).

Graphical abstract