Glomerular Hyperfiltration: An Early Marker of Nephropathy in Fabry Disease

Abstract

Background and objectives: Progressive nephropathy is one of the main features of Fabry disease (FD). It has been supposed that an early phase, clinically silent disease occurs in childhood and adolescence and is characterized by glomerular hyperfiltration (HF). Surprisingly, although HF has been reported in several studies, its prevalence is at present unknown. The focus of our study was to determine the prevalence of HF in a cohort of patients with FD and to identify the factors associated with a high risk of HF. Methods: To address this issue, a retrospective observational study of 87 patients with genetically confirmed FD was performed. HF was defined as an estimated glomerular filtration rate (eGFR) > 130 mL/min/1.73 m² corrected for age (> 40 years: –1 mL/min/1.73 m²/year). Results: HF occurred in 21 patients (24% of our population), and increased to 50% when only young adults were considered. Hyperfiltrating patients were younger and had lower proteinuria levels than those without HF. The prevalence of cardiovascular and other manifestations of FD was significantly lower in hyperfiltering patients. Conclusions: Our study showed a negative correlation between eGFR and age, and with proteinuria levels and the presence of cardiovascular and other manifestations of FD. These data favor the view that HF in Fabry patients could be related predominantly to a predisease state. Even in the absence of a “measured” GFR, HF should be regarded as an early marker of Fabry nephropathy, and its recognition and confirmation by true GFR seems a relevant feature to address the issue of the potential benefit of nephroprotective treatments at the early stage of Fabry nephropathy.

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

“…The detection of a major prevalence of GHF in the first quartile of age is coincident with the natural evolution of Fabry nephropathy in patients without specific treatment. A recent retrospective observational study in Italy showed a similar result with a GHF prevalence of 24% in a population of 87 FD patients (20).…”

“…In Argentina, a recent analysis of young patients with classic FD forms and mild or absent nephropathy showed urinary microRNAs suggestive of kidney fibrosis, even in non-albuminuric cases (22). Riccio et al reported that GHF may be an early marker of renal involvement in FD patients, even before the onset of signs, symptoms, or laboratory changes (20). Although proteinuria can be considered an indirect marker of GHF, there are situations where the urinary protein loss is due to alterations in the glomerular filtration barrier secondary to a glomerular disease rather than a consequence of the GHF per se.…”

Renal Manifestations of Fabry Disease: A Narrative Review

“…When injured, the result is glomerulosclerosis, indicative of irreversible damage to the glomeruli. [67][68][69] Endothelial cells contribute to the development of fibrosis, through luminal obstruction and ischemia. 70 The mesangial cells seem to play a less important role in the pathophysiology of nephropathy.…”

Biomarkers of Fabry Nephropathy: Review and Future Perspective

“…Some Fabry patients develop GFR loss before development of proteinuria [16]. Glomerular hyperfiltration may be a common feature in young Fabry patients and may be considered as an early marker of Fabry nephropathy [40], which masks impairment of renal function, although rare, a decline in GFR can already be seen in adolescence [41]. Slope of progression of renal insufficiency was correlated to the level of proteinuria and in addition, it was not linear as shown by Schiffmann et al, where they retrospectively analyzed the decline of eGFR.…”