Peer Reviewed

fabry disease

Renal Manifestations of Fabry Disease

Fabry disease is a rare, multisystemic genetic disorder that often results in end-stage kidney disease. In an effort to better understand the renal manifestations of Fabry disease, researchers conducted a narrative review examining various aspects of Fabry disease nephropathy, including histological alterations, treatment, and nephropathy implications.

The results indicated that Fabry disease nephropathy is associated with the progressive accumulation of GL3, emphasizing the importance of screening, early diagnosis, and prompt treatment. However, the authors note that Fabry disease often goes unnoticed and underdiagnosed, putting patients at a higher risk of adverse outcomes.

To discuss these findings further and examine their implications, Consultant360 reached out to study author Cassiano Augusto Braga Silva, MD, who is a nephrologist in the CSB unit in Feira de Santana, Brazil.


Consultant360: Your team conducted a narrative review of renal manifestations of Fabry disease. What prompted this research?

Cassiano Augusto: This narrative review was conducted to describe all aspects related to kidney involvement in patients with Fabry disease, with an emphasis on histological and clinical changes, and to describe the treatments currently available. Our aim was for this document to be a complete guide to assist physicians and other caregivers in making decisions based on the best therapeutic practices.

C360: Your review notes that Fabry disease nephropathy often goes unnoticed and underdiagnosed. Why is Fabry disease nephropathy an important consideration for health care practitioners who treat patients with Fabry disease?

CA: The first point to note is that unfortunately few doctors, including nephrologists, have adequate knowledge about Fabry disease. This is because it is a rare disease. Another important point is that the disease is characterized by many peculiarities, which can make its identification more difficult.

In many cases, the diagnostic delay is quite significant when there is already significant renal impairment. It is noteworthy here that Fabry disease nephropathy can be identified in many cases from laboratory changes that are widespread in clinical practice, such as values of creatinine (glomerular filtration rate) and proteinuria. What makes the dissemination of this knowledge urgent is that the earlier the therapies are initiated, the better the results and prognosis.

C360: What is the current standard of care for treating Fabry disease in regard to kidney function?

CA: Regarding Fabry disease nephropathy therapy, in general, medications of the class of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) are used to decrease proteinuria, optimize blood pressure (BP), and help slow the rate of progression of kidney disease. The gold standard of treatment, which is individualized per patient, is based on the specific therapy of the disease that seeks to replace or optimize the enzyme deficiency (lysosomal enzyme α-galactosidase A). It is worth emphasizing again that some patients do not reach the therapeutic objective of stabilizing or improving renal impairment because of a more advanced level of tissue damage when therapy is started.

C360: How does this narrative review add to the body of literature on Fabry disease?

CA: Our objective was to carry out a complete and updated review of the literature in search of all the most important information regarding Fabry disease, with an emphasis on renal involvement. We addressed the clinical, laboratory, histopathological aspects, new markers, and results of the most recent studies on the treatment of the disease. We believe that important data will serve as an updated resource for everyone who is interested in and treats patients with this rare disease, as well as those who support the global approach in a more secure and individualized way.

C360: What knowledge gaps remain concerning the renal manifestations of Fabry disease?

CA: The biggest gaps in knowledge involve the true role and usefulness of disease markers, both those already understood and those under study. New biomarkers are still needed for an earlier detection of nephropathy, which could help in a better prognosis of both the disease and kidney injury. The role of variants of uncertain significance has yet to be properly elucidated, given the enormity of variants that potentially cause the disease.

Because disease-specific therapy is relatively recent, more robust data on long-term outcomes are still lacking. The treatments in the study phase envision an evolution of the current therapy, with fewer adverse effects and better results. Another point not yet fully understood is the role of antibodies against the enzyme in patients being treated. The point that is not discussed, as with practically all diseases, is the importance of early detection and intervention in search of better evolution.



Silva CAB, Moura-Neto JA, Dos Reis MA, Vieira Neto OM, Barreto FC. Renal manifestations of Fabry disease: a narrative Review. Can J Kidney Health Dis. 2021;8:2054358120985627.