FSGS: Exploring Challenges, Investigating Treatments
In 2004, an 8-year-old boy was referred to the Kidney Clinic at Cincinnati Children’s for new-onset nephrotic syndrome with gross hematuria. Although the presence of the latter suggested the nephrotic syndrome’s cause was not minimal change disease, the child responded to a standard treatment course of steroids by going into remission. Nevertheless, relapses occurred quickly and he rapidly became steroid resistant, leading to a diagnostic kidney biopsy, which showed one globally sclerotic glomerulus and otherwise only minimal changes.
While not proving focal segmental glomerulosclerosis (FSGS), these pathological findings − paired with the child’s clinical course − were not inconsistent with FSGS. Accordingly, second- and third-line therapies, including courses of cyclophosphamide, mycophenolate mofetil and tacrolimus, were initiated without much success. Instead, multiple hospitalizations ensued, beginning at the age of 10, for infectious and thrombotic complications of the boy’s persistent nephrotic state and gradual deterioration of renal function.
Persistent nephrosis and progressive chronic kidney disease, in addition to related cardiac dysfunction, subsequently necessitated bilateral native nephrectomies (which confirmed the diagnosis of FSGS) and access placement for hemodialysis initiation. While undergoing an aggressive dialysis regimen, the boy’s nephrotic state resolved and his cardiac function stabilized, paving the way for a kidney transplant.
FSGS is one of the most common causes of end-stage renal disease in children and is associated with particularly high pre- and post-transplant morbidity. Most important, the disease recurs in approximately one-third of all cases, typically soon after transplantation, and can lead to graft loss.
Strategies to prevent or treat recurrent FSGS remain controversial and substantially resource-intense and include plasmapheresis and anti-CD20 antibody (rituximab) infusions, in addition to standard post-transplant care including immunosuppression. At Cincinnati Children’s, end-stage renal disease (ESRD) secondary to FSGS is managed in a step-wise, multidisciplinary approach led by Jens Goebel, MD, medical director of our Kidney Transplant Program. Our nephrology and transplant surgery teams are involved along with the pheresis service at the University of Cincinnati’s Hoxworth Blood Center.
- Genetic testing is arranged to identify patients with mutations known to be associated with FSGS (e.g., podocin and nephrin).
- Once chronic kidney disease has progressed significantly and nephrosis is treatment-resistant, native nephrectomies are performed to curtail urinary protein loss and allow early detection of post-transplant FSGS recurrence.
- Based on clinical, genetic and histopathological criteria, patients at high risk for post-transplant recurrence are identified.
- Extensive counseling and additional support are provided to patients and their families, preparing them for the potentially extremely complicated course of the disease.
- If a living kidney donor is available for a patient considered to be at high recurrence risk, access is placed for prophylactic pheresis three times a week for two weeks before the scheduled transplant.
- If there is evidence of FSGS recurrence, pheresis is resumed post-transplant and augmented by rituximab therapy.
At 12 years of age, the boy received a kidney transplant from his mother, which was complicated by immediate disease recurrence without compromise of graft function. Pheresis was accordingly continued, initially three times weekly, and gradually tapered based on the degree of proteinuria. After almost a year of therapy for FSGS recurrence, the boy was successfully weaned, has maintained good transplant function and has remained free of proteinuria. His cardiac function has normalized; he continues to receive standard immunosuppression to prevent rejection and is back in school.
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