New Treatments For FSGS -ASN Conference

FSGS 

Nephron
Idiopathic focal and segmental glomerular sclerosis or FSGS is one of the most common causes of non diabetic kidney disease in the world and also one of the least satisfying to treat due to the difficulty with initiating and maintaining a durable remission. For decades the standard of treatment has been steroid therapy in high doses given either daily or every other day. This results in significant toxicity which includes the development of diabetes mellitus, osteoporosis, personality changes, weight gain, easy bruising etc. Yet these negative effects of steroid therapy are outweighed significantly by the result of not treating FSGS as the disease will usually progress to end stage renal disease (with a requirement for dialysis and transplantation). Even after transplantation there is a risk of recurrence of the disease within hours after surgery in some patients.

If ever there was a nephropathy in need of new treatment options it would be FSGS.

NEW OPTIONS

• Oral dexamethasone for FSGS

Oral dexamethasone was found to be as effective as steroid therapy, not superior however. The side effect profile is very similar. It is unlikely that further studies will change the outlook for dexamethasone as an alternative therapy

• Rituximab

Rituximab in FSGS has had a stormy course with the safety of rituximab as a therapeutic option under scrutiny due to deaths from a rare condition known as plemorphic multifocal leucoencephalopathy. The first cases were seen in patients with lupus treated with rituximab. Response rates to rituximab have varied in different studies implying that perhaps there are certain patient specific factors which predispose for response to rituximab. The key for the future of rituximab will be identifying patients with FSGS who are likely to respond.

• Rosiglitazone

This drug is primarily used in the treatment of type 2 diabetes where it acts to reduce insulin resistance and enhance glucose uptake into skeletal muscle. The drug however has an antifibrotic effect which may be useful in FSGS this drug is currently undergoing phase I trials.

• Adalimumab

This drug is an inhibitor of tumour necrosis factor one of the major cytokines (hormone produced by cells that affect other cells ) that induces inflammation. Inhibition of TNF is a possible pathway for treating FSGS. The FONT II study will look at the efficacy of adalimumab in patients with FSGS.

• Retinoids

Wikipedia defines retinoids as " A class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth. Retinoids have many important and diverse functions throughout the body including roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes."

What that essential translates to is that retinoids are a group of molecules that alter the expression of a variety of genes some of these genes are important to the proliferation of cells within the kidney and may play a role in the mechanism of FSGS. Trials with accutane (a retinoid currently used for treatment of acne) are currently at phase II.

• Perfinidone

Which has been shown to be helpful in diabetic nephrosclerosis has shown some efficacy in FSGS as well. The drug is capable of altering the rate of decline of kidney function in FSGS however it does not induce remission. It also does not alter proteinuria.

So some hope exists for improving the treatment of FSGS but it is still early days for almost all of the above.