The kidney in Fabry's disease.

Fabry disease (FD) is an X-linked disease in which mutations of the GLA gene result in a deficiency of the enzyme α-galactosidase A and subsequent progressive, intralysosomal deposition of undegraded glycosphingolipid products, primarily globotriaosylceramide, in multiple organs. Progressive nephropathy is one of the main features of FD and is marked by an insidious development, with an overall rate of progression of chronic kidney disease (CKD) very similar to diabetic nephropathy. Untreated patients usually develop end stage renal disease in their 50s. The decline in renal function in FD is adversely affected by male gender, advanced CKD, hypertension and, in particular, severe proteinuria. Enzyme replacement therapy (ERT) has been shown to slow the progression of Fabry nephropathy. The current consensus is that ERT should be started in all men and women with signs of renal involvement.

Effects of switching from agalsidase Beta to agalsidase alfa in 10 patients with anderson-fabry disease.

Anderson-Fabry disease (AFD) is a multiorgan X-linked lysosomal storage disease that particularly affects the heart, kidneys, and cerebrovascular system. Current treatment is enzyme replacement therapy (ERT) with agalsidase beta (Fabrazyme(®), Genzyme Corporation, Cambridge, MA, USA) or agalsidase alfa (Replagal(®), Shire Human Genetic Therapies AB, Lund, Sweden). It was recommended that patients switch to agalsidase alfa due to a manufacturing shortage of agalsidase beta beginning in June 2009. This study assessed the effect of switching to agalsidase alfa on clinical outcomes in patients with AFD previously treated with agalsidase beta. Ten patients (seven male, three female) with genetically confirmed AFD and at least 48 months' continuous data collected during treatment with agalsidase beta 1 mg/kg every other week were switched to agalsidase alfa 0.2 mg/kg every other week for at least 20 months, with prospective clinical evaluations every 6 months. Pre-switch data was collected retrospectively from patient charts. Cardiac functional parameters were assessed using magnetic resonance imaging. Results showed that renal function was normal (estimated glomerular filtration rate ≥90 mL/min/1.73 m(2)) in 8 of 10 patients prior to agalsidase alfa and generally remained stable after the switch. Cardiac mass decreased significantly (p < 0.05 vs pre-ERT) after agalsidase beta and remained unchanged after switching to agalsidase alfa. Symptoms of pain and health status scores did not deteriorate during agalsidase alfa therapy. Adverse events were mostly mild and infusion related. In conclusion, switching to agalsidase alfa was relatively well tolerated and associated with stable clinical status and preserved renal and cardiac function.

Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.

BACKGROUND: Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. OBJECTIVE: This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. PATIENTS: Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). RESULTS: At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. CONCLUSIONS: Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.

Hepatitis C and kidney disease.

Hepatitis C virus (HCV) infection is often associated with kidney diseases such as membranoproliferative glomerulonephritis (MPGN), with and without cryoglobulinemia, membranous glomerulonephritis (MGN) or glomerulosclerosis (FSGN). The aim of our study was to determine the frequency of HCV with or without hypertransaminasemia in patients with chronic nephropathy in the predialytic phase. We tested 340 subjects with chronic renal insufficiency (CRI) from our hospital's nephrology outpatient clinic for anti-HCV antibodies. In positive subjects we tested for HCV RNA by PCR method, monitoring, for at least 4 months, common biohumoral parameters including transaminases (AST, ALT). Of the 340 subjects, 46 (13.5%) were positive for HCV RNA, and 8 of these (17%) showed constant alteration of transaminases. HBsAg was found in 8 of the total study population (2.3%), and none of these showed altered transaminases. Type II diabetes mellitus was found in 26% (12/46) of the HCV-RNA positive patients, and in only 12.5% (37/294) of the negative ones. The kidney diseases we found in the 46 HCV-RNA positive patients were: diabetic nephropathy in 11 (23.9%), MPGN in 7 (15.2%), MPGN + cryoglobulinemia in 2 (4.3%), interstitial nephropathy in 4 (8.7%), IgA mesangial GN in 3 (6.5%), hypertensive nephropathy in 2 (4.3%), focal and segmental GN in 1 (2.2%), urologic disease in 4 (8.7%), other (hematological, genetic, iatrogenic) in 3 (6.6%), unknown in 9 (19.6%). Our data show that the most frequent kidney diseases associated with HCV infection were diabetic related nephropathy and MPGN with and without cryoglobulinemia. HCV infection had a positive association with diabetes. It is interesting to note that in this study population the hepatitis C concomitant to kidney disease was unusually mild: only 4 of the 46 subjects (9%) showed clinical, biohumoral and ultrasound evidence of cirrhosis.