Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

Abstract

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

Fabry Disease: Current and Novel Therapeutic Strategies. A Narrative Review

“…When end-stage renal disease occurs, renal replacement therapy is required with either dialysis treatment or kidney transplantation [ 96 - 98 ]. Importantly, the risks of all-cause graft failure and all-cause mortality do not differ between FD patients compared to transplanted patients with other causes of end-stage renal disease [ 99 ]. Therefore, kidney transplant should be offered as an option in patients with FD, especially in the current era of ERT, which carries an additional protective role in terms of graft and patient survival [ 100 ].…”

Monogenic Kidney Diseases in Kidney Transplantation

“… 107 However, enzyme replacement therapy can lead to the formation of neutralizing antidrug antibodies, reducing the efficacy of therapy. 108 FD accounts for 0.2% of patients on hemodialysis. 109 KT is safe in FD, as recently confirmed by a meta-analysis pooling 424 patients.…”

“… 109 KT is safe in FD, as recently confirmed by a meta-analysis pooling 424 patients. 108 Decreased plasma globotriaosylceramide levels, stable kidney function, decreased left ventricular mass and improved cardiac contractility were reported among transplanted patients on enzyme replacement therapy. 110 To protect against the systemic accumulation of glycosphingolipids, enzyme replacement therapy should be continued on dialysis and after KT.…”

“… 110 To protect against the systemic accumulation of glycosphingolipids, enzyme replacement therapy should be continued on dialysis and after KT. 108 The development of enzyme replacement therapy antibodies seems to be rarer in patients with FD on immunosuppressive medications for KT. 111 Finding globotriaosylceramide deposits in the graft does not seem to impact on the outcome of the transplant.…”

Evaluation of Genetic Kidney Diseases in Living Donor Kidney Transplantation: Towards Precision Genomic Medicine in Donor Risk Assessment

“…Specific treatments (enzymatic replacement or pharmacologic chaperones) should be initiated as soon as a diagnosis is obtained which can change the prognosis of the disease [83]. Despite a recurrence rate of Fabry disease after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with and without Fabry disease [85,86], with continued enzyme replacement treatment in affected individuals post-transplantation. A detailed evaluation (slit lamp eye exam, leukocyte α-Gal A level) and genetic testing should be performed in living related donor candidates with a family history of Fabry disease due to the high risk of renal involvement.…”