Urinary Trypsin Inhibitor is a Marker of Renal Disease in Fabry’s Patients

Fabry’s disease is a rare X-linked lysosomal storage disordercaused by deficiency of 􀀀-galactosidase A1, that leads toaccumulation of glycosphingolipids in many cell types and tissues.The disease manifestation usually starts in childhoodand, in adulthood, the progression of the pathology may leadto renal and cardiac damages, and high propensity to developcerebral ischemic stroke resulting in decreased life expectancy2.Early biochemical markers of Fabry’s nephropathy, routinelyused in clinical settings, are microalbuminuria or proteinuria.These markers are useful for documenting the occurrenceof renal impairment, at an early stage, and indicate theneed to introduce the appropriate enzymatic replacementtherapy before renal damage becomes irreversible. Urinarytrypsin inhibitor (UTI) is a small chondroitin sulphate (CS)-proteoglycan whose levels are usually low in healthy individualsbut are increased in several pathological conditions includingrenal diseases3. Since renal damage is one of the majorcomplications of Fabry’s disease, the aim of this research wasto evaluate if the UTI excretion could represent a useful indicatorof early stage renal disease in these patients. UTI levelswere evaluated on both plasma and first-morning urine samplesfrom Fabry’s patients (n=22), sorted among patients withovert renal disease (RD patients, n=11) and patients that didnot show any obvious renal impairment (NRD patients, n=11),and age-and sex-matched, healthy controls (n=43). Overall,urinary UTI levels were significantly different betweenpatients and controls (+60%, p=0.005) due to higher UTIlevels in RD Fabry’s patients (+84%, p=0.0001). By subsortingRD group in patients with only proteinuria or renaldamage, no differences were evidenced demonstrating that theincrease of urinary UTI levels in Fabry’s patients may beanother biochemical marker of early stage renal disease inthese patients. No differences were evidenced in plasma levelsof CS isomers, highlighting a specific association between urinaryUTI levels and renal impairment. These results suggestthat urinary UTI level could represent a useful marker in monitoringrenal functionality in Fabry’s patients. Further studiesare needed to find out if urinary UTI levels could be an earliermarker of renal damage compared with proteinuria.