Analysis: Kidney Transplantation in Fabry Disease Has High Success Rate

Patients with Fabry disease (FD) who undergo kidney transplants have roughly the same rates of allograft and patient survival as transplant patients in the general population, according to new research.

The report is based on a review of 11 studies and more than 400 patients with the rare, X-linked lysosomal storage disorder. It was published in the journal Diseases.

Patients with FD exhibit a number of symptoms, including the potential for renal failure. Corresponding author Charat Thongprayoon, MD, of the Mayo Clinic, and colleagues, wrote that Fabry nephropathy is similar to diabetic kidney disease, and typically occurs in 3 phases. The first phase is glomerular hyperfiltration, which typically begins in childhood or adolescence. The problem most commonly evolves into proteinuria by the patient’s mid-30s. In the final phase, a patient can experience several renal diseases and eventually end-stage kidney disease.

There is currently no cure for Fabry, so treatment typically involves symptom management, enzyme replacement therapy (ERT), dialysis, and kidney transplantation. The latter has been somewhat controversial, however, according to Thongprayoon and colleagues.

“Some evidence suggests that kidney transplant increases serum α-gal A and urine α-gal A,” they wrote. “Graft failure secondary to substrate deposition has also been suggested.”

Yet, Thongprayoon and colleagues said it is difficult to know for sure since data has so far been limited.

In order to bring clarity to the question, the investigators conducted a comprehensive literature review of studies involving outcomes of kidney transplantation in patients with FD up through a cutoff of February 2020. A total of 424 patients were enrolled in the 11 studies, and the median follow-up of the studies ranged from 3 to 11.5 years post-transplantation.

Within that data set, the overall estimated rate of all-cause graft failure was 32.5%, graft failure before death was 14.5%, and allograft rejection were 20.2%.

When the data were refined to only include studies conducted after the availability of ERT in 2001, the rate of all-cause graft failure fell to 28.1%, graft failure before death fell to 11.7%, and allograft rejection remained at 20.2%. Biopsy-verified FD recurrence was 11.1%. Despite that risk, the investigators said, there was no statistically significant difference between all-cause graft failure in patients with FD versus patients without the disease.

After noting that kidney transplantation outcomes appear to have improved following the availability of ERT, Thongprayoon and colleagues also addressed whether or not ERT is warranted following transplantation. The answer is “yes,” they said, noting that the therapy appeared to be well-tolerated with minimal side effects.

The investigators also noted that medications associated with kidney transplantation may be beneficial to ERT.

“One of the challenges with ERT is the development of ERT antibodies, as this complicates treatment among Fabry disease patients,” they said. “In patients after kidney transplant, there appears to be a protective role of immunosuppressive medications on emergence of ERT antibodies.”

Not only did patients not develop new antibodies, patients who already had them experienced temporary suppression of antibodies, the authors said.

Though the overall findings were positive, the authors cautioned that the dataset was still relatively small, mostly male, and lacked robust data on patients’ comorbidities. Thus, they said, the findings should be treated cautiously and confirmed with later studies.

Reference

Suarez MLG, Thongprayoon C, Hansrivijit P, et al. Outcomes of kidney transplantation in Fabry disease: A meta-analysis. Diseases. 2020;9(1):2. Published 2020 Dec 23. doi:10.3390/diseases9010002