SCREENING DIAGNOSTICS OF FABRIC DISEASE AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE IN THE NORTH-WESTERN REGION OF RUSSIA

Abstract

Fabry disease (FD) is a progressive multi-organ disease leading to the development of cardiovascular and cerebrovascular complications and progression of renal failure. Nonspecificity of clinical signs often leads to late diagnosis of the FD that causes high diagnostic relevance of screening in high risk groups, particularly among patients with chronic kidney disease (CKD). According to the results of screening programs in many countries, the average prevalence of FD among patients with CKD is about 0.26%. THE AIM of this study was to investigate the prevalence of FD in patients with CKD in the northern west region of Russian Federation. PATIENTS AND METHODS. This prospective study assessed α-galactosidase A (α-Gal A) activity in dried blood spots in 1835 stage 1-5 CKD (85% – dialysis, 15% – pre-dialysis) patients, 74% males, mean age 55±12 years. The survey was carried out regardless of gender, age and primary diagnosis leading to CKD. The activity of α-Gal A more than 1.89 umol/l/hr was considered as normal. In the case of identifying the decreased activity of the enzyme the diagnosis was confirmed by GLA gene mutation analysis. RESULTS. The average level of α-Gal A was 5.39±2.69 umol/l/h. The level of α-Gal A was significantly higher in patients with pre-dialysis stages of CKD compared with patients receiving dialysis (7.5±3 vs 4.3±2.3 umol/l/h, p<0.001) as well as in males higher than in females (5.9±3.4 vs 3.4±2.3 umol/l/h, p <0.001). The decrease in α-Gal A activity was detected in 6 patients, of which 3 had the GLA gene mutations (c.427G>A, с.818Т>С, c.895G>C). One patient (p.508G> T) had a confirmed FD and received an enzyme-replacement therapy at the time of screening. All patients with identified FD were males treated by hemodialysis. Thus, the prevalence of FD in patients with CKD C5d was 1:392 (0.26%). A survey of relatives revealed the disease in two additional cases. CONCLUSION. The prevalence of Fabry disease in selected CKD patients of northern west region of Russian Federation is in the mean worldwide range. In all cases, the FD was not timely diagnosed, leading to serious organ damage and delaying the onset of enzyme replacement therapy. Thus, the screening of FD is necessary at the early stages of CKD.