Focal Sclerosis: Now What?
Back in January, I addressed the topic of childhood nephrotic syndrome, a common rare disorder. One of the forms that we often see in children with steroid-resistance is focal segmental glomerulosclerosis (FSGS).
What is FSGS?
FSGS can be diagnosed only after a kidney biopsy. The term describes what we see in the kidney:
- Focal, meaning only some of the filtering units (glomeruli) have lesions
- Segmental, meaning affected glomeruli have only a portion of each tuft involved
- Glomerulosclerosis, meaning glomerular scarring
The cartoon shows that a portion of the blood vessels in the glomerular tuft become choked by scar material. How this leads to proteinuria remains unclear.
What causes FSGS?
A number of diseases may cause secondary FSGS. The disorder has been associated with obesity, and excess body fat may be a secondary cause. Primary FSGS means that no known secondary cause can be identified.
A variety of mechanisms for primary FSGS have received scientific attention. Gene mutations in kidney proteins may predispose some patients to this disorder. Others may develop circulating factors in the blood that promote proteinuria and scarring. Blood tests may be used to check these possibilities.
What treats FSGS?
If a secondary cause is identified for FSGS, its should be treated. If proteinuria continues after treatment, then other therapies should be considered, especially those that ameliorate the proteinuria.
Patients with primary FSGS have often failed a course of steroids by the time a biopsy is performed. Next line therapies include calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate (Cellcept), intravenous steroids, or chemotherapy drugs. The latter category includes rituximab (which I blogged about at WhizBANG!), a humanized antibody that can produce long-lasting remissions in patients with FSGS, even in those whose disease recurs after transplantation. Some centers use plasma exchange, especially if heavy proteinuria develops immediately after transplantation.
Other treatments may treat symptoms or reduce the progression of FSGS. Normalizing blood pressure remains important in any kidney disease, especially with therapies that suppress angiotensin II (angiotensin converting enzyme inhibitors or angiotensin receptor blockers). Diuretics can help control the swelling that accompanies nephrotic syndrome, as will a low-salt diet. Children with nephrotic syndrome may have elevated blood cholesterol and lipids that require changes in the diet or additional medications. Finally, loss of protein in the urine increases risk of blood clots and infections. The latter can be a big problem when these children also receive drugs that suppress the immune system.