Summary

A systematic review and meta-analysis of immunosuppressant treatment in primary focal segmental glomerulosclerosis (FSGS) demonstrated reduced proteinuria and improved kidney function; however, a need for better clinical trials remains¹

Background

Focal segmental glomerulosclerosis (FSGS) is a rare renal disease that can lead to decreased kidney function and chronic kidney failure.² It can be classified as a primary, secondary, or genetic form.²

Primary FSGS is thought to be caused by a putative circulating factor that can lead to podocyte injury.³ It usually presents with sudden-onset, severe nephrotic syndrome.³

First-line treatment for primary FSGS with nephrotic syndrome is corticosteroids.⁴ Those who relapse or remain persistently nephrotic despite conservative therapy may require more aggressive treatments with other immunosuppressive treatments.⁴

The efficacy and safety of immunosuppressive treatments in primary FSGS are yet to be established, and there is a need for a more recent synthesis of the latest data.¹  

Aim

The objective of this systematic review was to evaluate the current information on the clinical efficacy and safety of immunosuppressive treatments in primary or idiopathic FSGS.¹

Approach

A comprehensive search of peer-reviewed literature was conducted across several databases.¹ The systemic literature review assessed population, intervention, comparator, and outcomes strategy.¹

Because there are few randomized-controlled trials (RCTs) that have assessed the efficacy of immunosuppressive treatments in primary or idiopathic FSGS, other study designs were included.¹

A series of inclusion and exclusion criteria were applied, and the final set of publications underwent a data extraction by two independent investigators.¹

Findings

The initial search identified 2,410 publications¹

Of the publications identified, 98 were included in the narrative synthesis and 33 were quantitatively evaluated.¹

Most patients experienced a significant reduction in daily proteinuria at 12 months¹

In the 14 studies that assessed daily proteinuria, patients treated with immunosuppressants demonstrated a significant reduction in daily proteinuria of >50% from baseline (ratio of mean [ROM]: 0.36; 95% confidence interval [CI]: 0.20-0.47).¹

There was a more robust and significant decrease in daily proteinuria at 12 months versus 6 months (ROM: 0.27; 95% CI: 0.16-0.44 vs ROM: 0.69; 95% CI: 0.41-1.16).¹

Reductions in estimated glomerular filtration rate (eGFR) were significant at various timepoints¹

Of the 20 studies that reported eGFR, the baseline mean value was 96.8 mL/min/1.73 m².¹ At any time point after follow-up, there was a mean significant decrease of 7.61 mL/min/1.73 m² (mean difference: -7.61; 95% CI: -14.98 to -0.25).¹

Statistical significance was also seen upon stratifying the pooled studies, however, the correlation between follow-up length and the observed effect size was unclear.¹

Safety and tolerability data were limited in the available studies¹

Hypertension (n=21 studies) and infections (n=20 studies) were the most common adverse events (AEs) across studies.¹ There were limited reports of hyperkalemia (n=1 study).¹

Key takeaway

This systematic review highlights the limited evidence currently available for primary FSGS.¹ Findings from the review demonstrated that immunosuppressant treatments reduced proteinuria and improved kidney function.¹ However, there is still a need for better-designed and more controlled studies to assess the effects of immunosuppressive treatment on primary FSGS.¹

Footnotes

AE, adverse event; CI, confidence interval; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; RCT, randomized-controlled trial; ROM, ratio of mean.

MA-DS-24-0038 | October 2024