Efficacy and Safety of ACE Inhibitor and Angiotensin Receptor Blocker Therapies in Primary Focal Segmental Glomerulosclerosis Treatment: A Systematic Review and Meta-Analysis

Summary

A systematic review and meta-analysis of the safety and efficacy of renin-angiotensin-aldosterone system (RAAS) inhibitors in focal segmental glomerulosclerosis (FSGS)¹

Background

Primary focal segmental glomerulosclerosis (FSGS) is a rare condition that causes kidney scarring and leads to chronic kidney failure.^1-3

Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB), are routinely used to reduce proteinuria in proteinuric kidney diseases.^1,3

However, the effects of RAAS inhibitors on kidney outcomes, such as proteinuria, glomerular filtration rate (GFR), and kidney survival, remain unclear in patients with primary FSGS.¹

Aim

The goal of this systematic literature review was to assess the efficacy and safety of RAAS inhibitor therapy on kidney outcomes in patients with primary or genetic FSGS.¹

Approach

The authors searched PubMed, Embase, and the Cochrane Library for clinical studies in primary or genetic FSGS up to April 2019.¹

Inclusion criteria encompassed studies of RAAS inhibitor monotherapy or combination therapy reporting¹:

Findings

Overall evidence base

Of the 28 studies included, most were real-world evidence (RWE) studies that assessed combination use with RAAS inhibitors, mainly immunosuppressants.¹

Proteinuria reduction

In patients treated with RAAS inhibitor monotherapy, proteinuria decreased by an average of 32%.¹ In patients treated with a RAAS inhibitor combined with other treatments, a 72% proteinuria reduction was observed from baseline to the last reported follow-up (ratio of means [ROM]: 0.24; 95% CI, 0.08-0.75).¹

Notably, only one controlled study prospectively assessed the effects of RAAS inhibitors combined with immunosuppressive therapies versus RAAS inhibitors alone (prednisone and ACEi/ARB vs ACEi/ARB alone).⁴ Findings demonstrated that adding immunosuppressants to RAAS inhibitors led to a stronger reduction in daily proteinuria than treatment with RAAS inhibitors alone (mean difference [MD]: −0.41 g/d; 95% CI, −0.46 to −0.36).⁴

Kidney function

A meta-analysis of four studies found no significant change in kidney function from baseline to the last reported follow-up, whether RAAS inhibitors were used alone or in combination¹:

Findings are limited by high variability, few studies, and no trials of RAAS inhibitors alone; results should be interpreted cautiously.

Kidney survival

A meta-analysis suggested that RAAS inhibitors combined with other treatments may reduce the risk of ESKD or kidney failure by about 58% (HR 0.42; 95% CI 0.30-0.60; P<0.001).¹

No study evaluated the impact of RAAS inhibitor monotherapy on ESKD or eGFR, limiting assessment of their independent effect on kidney failure progression.¹

Safety

RAAS inhibitors were generally well tolerated.¹ Reported adverse events were infrequent and mild when RAAS inhibitors were used alone.¹

Overall study limitations

Limitations included heterogeneity in study design, patient populations, and treatment regimens, all of which impacted data interpretation.¹

Key takeaway

RAAS inhibitor monotherapy is associated with proteinuria reduction and stable kidney function in primary FSGS.¹ When combined with immunosuppressive agents, greater reductions in proteinuria are observed.¹

However, limitations in study design and patient heterogeneity prevent definitive conclusions about long-term renal benefit of RAAS inhibitor monotherapy.¹

Footnotes

This systematic literature review was funded by Travere Therapeutics, Inc. Please see the publication for the full list of disclosures.

ACE, angiotensin-converting enzyme; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; FSGS, focal segmental glomerulosclerosis; GFR, glomerular filtration rate; MD, mean difference; RAAS, renin-angiotensin-aldosterone system; RAASi, renin-angiotensin-aldosterone system inhibitor; ROM, ratio of means; RWE, real-world evidence.

MA-DS-25-0064 | November 2025