RESUMO
BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disease causing progressive loss of target organ function. All renal cell types are involved from the early stages, even before clinical signs can be detected. FD-specific therapies can stop/mitigate disease progression. Thus, it is important to validate early markers of renal lesions so that they can be adopted as criteria for timely treatment initiation. MATERIALS AND METHODS: We retrospectively analyzed and extensively evaluated 21 FD case patients; this evaluation included a kidney biopsy. We looked for the influence of pathological findings on the management of FD patients. In addition, we investigated the association between general and FD-specific features and long-term patients' outcomes. We defined a combined endpoint as being at least one of the following: 50% decrease of estimated glomerular filtration rate (eGFR) from baseline, kidney failure (KF), end-stage kidney disease (ESKD), or death and mortality. RESULTS: Our cohort of 21 FD patients (11 males and 10 females) was stratified according to the presence of the combined endpoint: group 1 (n = 15) included patients without the combined endpoint, while group 2 (n = 6) patients reached the combined endpoint outcome. Patients from group 2 presented lower mean baseline eGFR (72.2 ± 38.7 mL/min/1.73 m2 vs. 82.5 ± 26.4 mL/min/1.73 m2) without statistical significance (p = 0.44), but significantly (p = 0.22) higher median baseline proteinuria (2.7 g/24 h vs. 0.4 g/24 h). Specific lysosomal deposits were identified in all patients. Segmental sclerosis was present in all patients with the combined endpoint and in only 33% of patients without the combined endpoint (p = 0.009). Global sclerosis and interstitial fibrosis were present in both groups, with no significant differences. A total of 15 out of the 16 treatment-naïve patients (7 males and 9 females) started FD-specific therapy after kidney biopsy. Treatment was initiated in all male FD patients and in 8 female patients. In 2 females, pathological findings in kidney biopsy offered important reasons to start FD treatment, although specific criteria of the Romanian protocol for prescription of FD-specific therapy were still not fulfilled. Cox univariate analysis showed that every increase in 24 h proteinuria with 1 g is associated with a 65% risk of developing the combined endpoint (HR = 1.65; 95%CI: 1.05-2.58; p = 0.02), and that the presence of segmental sclerosis increased the risk of developing the combined endpoint by 51.3 times (HR = 51.3; 95% CI: 95% CI: 1.67-103.5; p = 0.01). Kaplan-Meier analysis showed that the cumulative risk of developing the combined endpoint was higher in patients in whom segmental sclerosis (100% vs. 0%, log-rank test, p = 0.03) was present. CONCLUSIONS: Histological evaluation is an important tool for the detection of early kidney involvement and provides additional support to the early initiation of FD-specific therapy. Presence of segmental sclerosis can predict the long-term outcomes of kidney disease deterioration and mortality and may be used as an early indicator of disease progression. Additionally, in the absence of other criteria according to current guidelines, specific FD renal lesions as revealed by kidney biopsy might become a distinct criterion to initiate FD therapy.
RESUMO
AIM: This is a retrospective, observational study regarding the experience of the Fundeni Clinical Institute in the application of the Molecular Adsorbents Recirculating System in patients with liver failure. METHOD: From January 2002 until December 2007, we performed 50 MARS sessions in 27 patients, mean age 38.96+/-19.58 years. The etiology of liver failure was as follows: acute liver failure (ALF) in 7 patients, acute-on-chronic liver failure (AoCLF) in 10 patients, post-liver transplantation in 8 patients, and post-hepatectomy in 2 patients. RESULTS: We noticed the following clinical effects: improvement in general condition, in neurological status, marked regression of jaundice and pruritus, improvement in renal function and in hemodynamic status. Of the 7 patients with ALF, 3 patients (42.8 %) survived due to their own liver recovery. Only 2 patients (20%) with AoCLF survived. In this group, one patient was transplanted, one patient is alive, and the mean survival of the remaining patients was 24.5+/-34.6 days. In the post-liver transplantation group, one patient was retransplanted, one patient is alive and the mean survival of the other 6 patients was 28.5+/-39.8 days. One patient with post-hepatectomy liver failure presented spontaneous liver recovery. CONCLUSION: MARS therapy was well tolerated by the patients. MARS therapy efficiently removed water soluble and albumin-bound toxins. The unfavorable prognostic factors were the association with multi organ failure and sepsis.