Emerging therapeutic strategies for minimal change disease and focal and segmental glomerulosclerosis

ABSTRACT

Introduction: Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppressants and antiproteinuric drugs. Recently, Rituximab, a humanized monoclonal antibody (mAb) has emerged as a potential treatment for steroid or calcineurin inhibitor-dependent patients; it has however demonstrated lower efficacy in those with nephrotic syndrome that is resistant to the above indicated drugs.

Area covered: Analysis of ongoing and already completed clinical trials, retrieved from clinicaltrials.gov, clinicaltrialsregister.eu and PubMed involving new therapies for nephrotic syndrome secondary to MCD and FSGS.

Expert opinion: The most promising drugs under investigation for MCD and FSGS are mAbs. We are hopeful that new therapeutic options to treat multi-drug resistant MCD and FSGS will emerge from currently ongoing studies. What appears certain is the difficulty in enrolling patients affected by orphan renal diseases and the selection of valid endpoints in clinical trials, such as kidney failure.

KEYWORDS:

• Focal and segmental glomerulosclerosis
• FSGS
• MCD
• minimal change disease
• nephrotic syndrome
• novel therapies

Article highlights

• MCD and FSGS are two of the major causes of NS and are currently treated with steroids or other immunosuppressant therapies, according to KDIGO guidelines.

• Monoclonal antibodies, among which the most interesting are rituximab, ofatumumab, adalimumab, fresolimumab and bleselumab, showed positive results in reducing proteinuria in small cohorts. While rituximab effects have also been confirmed by larger trials, ofatumumab and fresolimumab. Adalimubab had conflicting results in FONT and FONT II trials, while bleselumab efficacy on posttransplant FSGS is currently under investigation.

• Other trials are currently investigating the nephro-protective potential of drugs like ACTHAR gel, IL-2, losmapimod, abatacept, D galactose, N-acetyl mannosamine (ManNAc), valproic acid, retinoids, bardoxolone, ERAs, which are employed in other diseases, but first results of some of them are conflicting or even negative.

• Some studies are focused on drugs administered only in Asian countries like mizoribine, levamisole, Tripterygium wilfordii, or Huai Qi Huang, in order to demonstrate their efficacy in larger cohorts.

• Finally, stem cells are a promising strategy under investigation, considering their possible implications in treating chronic or degenerative diseases, although trials are at very early stages.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.