Fabry disease—what cardiologists can learn from the nephrologist: a narrative review

Abstract

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder resulting in decreased or absent activity of the lysosomal enzyme alpha-galactosidase A. Subsequent accumulation of storage material can occur in virtually all cells of the body. Organs and structures affected by storage material deposition include the heart, the kidney, the central and peripheral nervous system and the cornea of the eyes. Progressive cardiac hypertrophy, arrhythmias, cardiac fibrosis, heart failure and cardiac death are common characteristics of cardiac involvement. Renal depositions of glycosphingolipids are already detectable in childhood. An early clinical sign of Fabry renal involvement is albuminuria, often preceding a detectable loss of kidney function.Later in life Fabry patients may exhibit a progressive decline of their kidney function leading to end-stage renal disease (ESRD). The clinical presentation of Fabry patients regarding renal involvement depends on the underlying mutation in the GLA gene. Classically affected males typically show a gradual decrease in kidney function, patients with mild or late onset mutations as well as a subgroup of females may exhibit only little or no renal abnormalities. This review summarizes the characteristics of renal involvement in FD, the diagnostics necessary to evaluate the degree of renal impairment and possible treatment options.

Clinical Characteristics, Renal Involvement, and Therapeutic Options of Pediatric Patients With Fabry Disease

“…Proteinuria (defined as the urine protein to urine creatinine ratio UPCR) even if it is not a sensitive biomarker for early kidney injury in Fabry nephropathy, is clinically one of the most often used biomarkers of Fabry nephropathy ( 68 , 100 ). Based on the study of Mehta et al that included 366 patients with Fabry from 11 European countries, the most frequently reported sign was proteinuria, which was found in 44% of hemizygous males and 33% of heterozygous female patients ( 101 ).…”

“…Based on the study of Mehta et al that included 366 patients with Fabry from 11 European countries, the most frequently reported sign was proteinuria, which was found in 44% of hemizygous males and 33% of heterozygous female patients ( 101 ). The degree of proteinuria is an independent risk factor for the extent of declining renal function over time ( 68 , 100 ). Increased levels of proteinuria before the starting of ERT may be used to predict the renal outcome.…”

“…Increased levels of proteinuria before the starting of ERT may be used to predict the renal outcome. As it was reported that cases with more severe proteinuria progress more quickly to ESRD compared to those with mild proteinuria, therefore, treatment of Fabry nephropathy should aim to decrease proteinuria ( 100 , 102 ). Progression of proteinuria, especially to levels > 1 g/day is a strong predictor of progression to ESRD in Fabry disease ( 73 ).…”

“…It was reported that proteinuria may not be evident in all cases with advanced kidney disease, and not correlate with GFR decline ( 98 ). Nephrotic range proteinuria is rare in Fabry patients ( 100 ). Proteinuria may start during childhood, even in the first decade of life ( 60 , 103 ).…”

“…Albuminuria is the most common clinical sign of renal involvement in patients with Fabry disease, often preceding a detectable loss of kidney function, and is related to glomerular and podocyte injuries ( 6 , 97 , 100 , 105 ). Albuminuria is not a sensitive biomarker for early kidney damage as it did not discover subclinical phases, as it is detectable only if glomerular podocyte damage is present ( 6 ).…”