Kidney Biopsy for Fabry Disease Treatment Indication

Patients with Fabry disease face progressive decline in kidney function, as well as disorders of the nervous system and the heart. Disease progression may be stopped or mitigated with specific therapy, but results depend significantly on early initiation of treatment.

Kidney biopsy in patients with Fabry disease carries crucial diagnostic, prognostic, and therapeutic implications. In some countries, renal biopsy evidence related to Fabry disease is a criterion for reimbursement for Fabry disease-specific therapy. Criteria for initiating Fabry disease specific therapy related to renal involvement include estimated glomerular filtration rate (eGFR) <80 mL/min/1.73 m² and/or proteinuria >300 mg per day.

Elena Emanuela Rusu and colleagues in Romania conducted a retrospective study to examine clinical and histologic aspects of renal involvement in untreated female patients diagnosed with Fabry disease by genetic test between 2015 and 2021 in a single center. Results of the study were reported at the European Renal Association 59th Congress in a presentation titled Kidney Biopsy in Females With Fabry Disease Is an Important Tool to Establish the Indication for Fabry-Specific Therapy.

Serum creatinine, albumin creatinine ratio, and proteinuria were measured to assess biologic renal manifestations. The presence of neurological involvement was determined by clinical exam, electroneurographic examination, and brain magnetic resonance; heart manifestations were assessed by echocardiography., electrocardiogram (ECG), ECG Holter, and cardiac magnetic resonance

Light and electron microscopy were utilized to analyze kidney biopsy specimens. The International Study Group of Fabry Nephropathy Score Sheet was used to evaluate specific renal Fabry disease lesions, as well as general lesions of progression.

From a total of 25 female patients, the study included 11 patients who had a kidney biopsy performed. Mean age at time of diagnosis was 47.7 years; mean age at symptom onset was 36.1 years. Mean eGFR was 72.7 mL/min/1.73 m² and mean proteinuria was 0.72 mg/day. The average Mainz score was 16.6. Five patients had heart involvement and five had neurological manifestations. Comorbidities included arterial hypertension (6 patients), diabetes mellitus (1 patient), and obesity (2 patients).

All kidney biopsies showed lysosomal accumulation in the podocytes, in the parietal cells of the Bowman capsule, and in the tubules. In nine cases, vascular inclusions were found. There was segmental glomerular sclerosis in four cases, global glomerular sclerosis in three cases, interstitial fibrosis in six cases, tubular atrophy in five cases, arteriosclerosis in four cases, and arteriolar hyalinosis in five cases.

Regarding national criteria for initiation of Fabry disease therapy, five patients fulfilled the renal criteria, three presented criteria for other organ involvement, and three (mean age 37.7 years) did not fulfill any criteria.

The researchers noted that even in the six patients without renal criteria for Fabry disease therapy, the kidney biopsy showed Fabry disease-specific lesions (lysosomal accumulation) in all cases.

In conclusion, the researchers said, “The data from our small cohort of females with Fabry disease underline the importance of kidney biopsy for detection of early kidney involvement and provide additional support to the consideration of early initiation of Fabry disease-specific therapy, potentially improving long-term outcomes. Thus, proof of specific Fabry disease lesions as revealed by kidney biopsy could become a distinct criterion for initiation of Fabry disease therapy, in the absence of other criteria according to current guidelines. Future studies are necessary in order to specify the role of renal histology in the establishment of the proper timing to start the Fabry disease treatment, especially in young patients.”

Source: Rusu EE, Zilisteanu D, Ciobotaru LM, et al. Kidney biopsy in females with Fabry disease is an important tool to establish the indication for Fabry-specific therapy. Abstract of a presentation at the 59th European Renal Association Congress 2022 (Abstract M0028), Paris, France, May 19-22, 2022.