Predictors of clinical events in patients with Fabry disease: the role of chronic kidney disease

Fabry disease is a rare disorder characterized by high frequency of severe organ manifestations in young patients. Aim. To determine predictors of clinical events in patients with Fabry disease. Materials and methods. We recruited 100 adult (over 18 years) patients with Fabry disease that was confirmed by enzymatic and genetic studies. The main outcome was a composite of end - stage renal disease, cardiac (arrhythmia and cardioverter/pacemaker implantation) and cerebrovascular (transient ischemic attack, stroke) events. Kaplan-Meier analysis was performed for event - free survival. Cox regression model was used to examine the risk of composite endpoint. Results and disscussion. Forty - seven of the 100 patients (38 males and 9 females) experienced clinical events. The median age of the first event was 39 [32; 49] years. In Kaplan-Meier analysis, the age of the first event was significantly lower among men than women, (p<0.0001), patients with decreased glomerular filtration rate (eGFR) at the time of first detected kidney involvement (p=0.002) and patients with proteinuria (p<0.0001). Using Cox regression analysis, eGFR<60 ml/min/1.73 m2 (HR 3.79, 95% CI 1.87-7.66, p<0.0001), high proteinuria (HR 1.29, 95% CI 1.04-1.59, p=0.022) and increased left ventricular myocardial mass index (LVMMI, HR 1.01, 95% CI 1.002-1.02, p=0.015) were associated with greater risk of developing a composite event after adjustment for gender and age. Eleven males were died. All deceased patients had end - stage renal disease. High proteinuria (HR 1.57, 95% CI 1.05-2.35, p=0.029) and increased LVMMI (HR 1.006, 95% CI 1-1.012, p=0.038) were predictors of death after adjustment for gender, but lost its effect on event occurrence after adjustment for hemodialysis duration. The type of mutation in the GLA gene was not a predictor of clinical events. Conclusion. Chronic kidney disease was an important risk factor of clinical events. Increased LVMMI and high proteinuria were both predictors of death and composite event. Estimated GFR lower than 60 ml/min/1.73m2 at the time of first detected kidney involvement was also associated with greater risk of developing a composite event.

Fabry disease, chronic kidney disease, survival, risk factors