The use of lanreotide in polycystic kidney disease: a single-centre experience.

The secretion of large volumes of fluid into cysts and changes in the structure and mobility of the cilia of the renal tubular epithelium can lead to nephromegaly. This in turn often causes a deterioration of kidney function and arterial hypertension. In recent clinical studies, somatostatin analogues have demonstrated efficacy in isolated polycystic liver disease and, to a lesser extent, in polycystic kidney disease. Since the publication of these clinical studies, several patients have been referred to us for somatostatin analogue treatment. Here, we report our experience with 6 patients who were treated with lanreotide autogel 120 mg every 4 weeks over 6, 12 or 18 months and were longitudinally followed using CT scans without contrast agents, to evaluate the total bilateral kidney volume. We observed a mean decrease in volume of 4%, with mild to moderate side effects.

Enzyme replacement therapy and renal function in 201 patients with Fabry disease.

AIM: Fabry disease is a rare lysosomal storage disorder caused by deficient activity of alpha-galactosidase A, resulting in progressive cellular accumulation of glycolipids, which may ultimately result in endstage renal disease. We examined the effects of enzyme replacement therapy (ERT) with Agalsidase-alpha on renal function using data from a large international database, the Fabry Outcome Survey (FOS). METHODS: This analysis was based on 1,040 serum creatinine measurements in 201 patients with Fabry disease, aged 20 - 60 years, with serum creatinine concentrations of less than 2 mg/dl and duration of ERT of up to 4.7 years. Both pretreatment and treatment data were used to examine independent predictors of changes in serum creatinine. In a second approach longitudinal serum creatinine measurements from 1 year before treatment, at baseline and 1 and 2 years after the start of treatment were analyzed in 20 patients with chronic kidney disease (CKD) Stage 2 and 3. RESULTS: We found an independent negative association between serum creatinine and time on Agalsidase-alpha treatment (p < 0.05). Renal function declined significantly (p < 0.05) in the year before treatment. After 1 year of treatment, however, the decline in estimated glomerular filtration rate had been halted, and renal function was preserved for up to 2 years. CONCLUSIONS: In conclusion, ERT with Agalsidase-alpha is associated with decrease of serum creatinine and may prevent the deterioration of renal function in patients with Fabry disease.

Fabry disease: overall effects of agalsidase alfa treatment.

BACKGROUND: Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. The Fabry Outcome Survey (FOS) is a European outcomes database which was established to collect data on the natural history of this little-known disease and to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. This paper presents the first analysis of the FOS database on the effects of ERT on renal function, heart size, pain and quality of life. DESIGN: The effects of 1 and 2 years of ERT with agalsidase alfa on renal function (assessed by estimated glomerular filtration rate), heart size (assessed by echocardiography), pain (assessed by the Brief Pain Inventory) and quality of life (assessed by the European Quality of Life Questionnaire EQ-5D) were analyzed in a cohort of 545 patients, 314 of whom were receiving treatment (188 for at least 12 months and 92 for at least 24 months; mean duration of treatment, 17 months; maximum duration, 56 months). RESULTS: Treatment with agalsidase alfa stabilized renal function in patients with a mild or moderate deterioration in renal function at baseline, reduced left ventricular size in patients who had an enlarged heart at baseline, and improved pain scores and quality of life. These improvements were similar in hemizygous men and heterozygous women with Fabry disease. CONCLUSIONS: Enzyme replacement therapy with agalsidase alfa leads to significant clinical benefits in patients with Fabry disease, and treatment is likely to alter the natural history of this disorder.

Relief of gastrointestinal symptoms under enzyme replacement therapy [corrected] in patients with Fabry disease.

Gastrointestinal symptoms, including diarrhoea and abdominal pain, are one of the earliest and most frequently reported signs of Fabry disease, a rare X-linked lipid storage disorder. As the disease progresses, renal, cardiac and cerebrovascular complications develop, resulting in more serious symptoms and early mortality. The present study evaluated the effects of enzyme replacement therapy (ERT) with agalsidase alfa on the gastrointestinal symptoms of Fabry disease. Following 6 months of treatment, both the severity ( p < 0.02) and frequency ( p < 0.02) of abdominal pain decreased. For those patients who had received agalsidase alfa for more than 6 months, the observed improvement was generally maintained. This is the first study indicating a significant beneficial effect of ERT on gastrointestinal symptoms in a group of patients treated for Fabry disease.

Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey.

BACKGROUND: Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. In response to the recent introduction of enzyme replacement therapy, the Fabry Outcome Survey (FOS) was established to pool data from European clinics on the natural history of this little-known disease and to monitor the long-term efficacy and safety of treatment. This paper presents the first analysis of the FOS database and provides essential baseline data against which the effects of enzyme replacement can be measured. DESIGN: Baseline data from a cohort of 366 patients from 11 European countries were analysed in terms of demography and clinical manifestations of Fabry disease. RESULTS: Misdiagnosis of Fabry disease is common, and the mean delay from onset of symptoms to correct diagnosis was 13.7 and 16.3 years in males and females, respectively. Although previously thought to have serious manifestations only in hemizygous men, the FOS database has confirmed that females heterozygous for Fabry disease are similarly affected. Furthermore, signs and symptoms of Fabry disease may be present from early childhood. CONCLUSIONS: With the advent of enzyme replacement therapy, it is important that general practitioners and physicians in a range of specialties recognize the signs and symptoms of Fabry disease so that effective treatment can be given. Baseline data from FOS demonstrate that enzyme replacement therapy should not be restricted to hemizygous men, but should be considered for both heterozygous females and children.

Effects of enzyme replacement therapy with agalsidase alfa on glomerular filtration rate in patients with Fabry disease: preliminary data.

UNLABELLED: Progressive deposition of globotriaosylceramide results in severe complications involving the kidney, heart and brain in both hemizygous male and heterozygous female patients with Fabry disease. Analysis of renal data from FOS--the Fabry Outcome Survey--suggests that enzyme replacement therapy with agalsidase alfa can significantly improve renal function in patients with Fabry disease, at least in those with a mild decrease in glomerular filtration rate, and may also be able to slow down the natural decline in renal function in patients with a moderate reduction in glomerular filtration rate. CONCLUSION: Initial results from the large cohort of patients within FOS indicate that treatment with agalsidase alfa has beneficial effects on kidney function in patients with Fabry disease.

B-cell response to a standardized breakfast in end-stage renal failure.

Twelve uremic patients (U) on regular hemodialysis were submitted to a standardized test meal. In comparison with normal controls (C), U patients demonstrated a slight increase of HbA1 level and a definite elevation of fasting plasma C-peptide immunoreactivity. They showed glucose intolerance at 60 and 120 min. This was associated with an inappropriate insulin response as evidenced by a significantly lower insulin/glucose index at 60 min. U patients were tested again during a hemodialysis session in order to reduce the 60-min glucose intolerance. Six patients (U1) were selected because they exhibited mean fasting and 60-min glucose values similar to those of the controls. In these conditions, the insulin response at 60 min was significantly decreased in comparison to basal conditions and this could not be accounted for by a concomitant decrease of plasma alpha-aminonitrogen values. It is concluded that, in uremic patients, glucose intolerance is associated with an inappropriately low B-cell response.

Comparison of three hemodialysis procedures with unipuncture.

Dialysis efficiency estimated by the decrease in urea, creatinine and phosphorus serum concentrations is higher with the double-lumen single-needle method, compared to the single-lumen needle unipuncture methods. This increased efficiency is related to a higher blood flow rate through the dialyser. Provided the superficial veins are not too small and/or tortuous, the double-lumen needle appears as a safe, simple and rewarding device and may be used in most patients on regular dialysis treatment.