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Fabry disease is an X-linked lysosomal disease caused by mutations of the alpha-galactosidase A (GLA) gene at chromosome subband Xq22.1. To date, more than 600 genetic mutations have been identified to determine the nature and frequency of the molecular lesions causing the classical and milder variant phenotypes and for precise carrier detection. We report here a Fabry family (mother, son and daughter) where the alpha-galactosidase A defect was associated with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Mutation analysis revealed for the GLA gene the presence of a new mutation, i.e., a small deletion (c.452delA) on exon 3 and for the G6PD gene the presence of 2 mutations, p.V68M (G6PD Asahi, G6PD A+) and p.N126D (G6PD A+) on exon 3 and exon 4, respectively.

We present the case of a 54-year-old man with multicystic kidney and concomitant Anderson-Fabry disease. He was referred to our hospital with multiple renal and hepatic cysts, without apparent family history of autosomal dominant polycystic kidney disease. His clinical history suggested Anderson-Fabry disease, so an extensive work-up for Anderson-Fabry disease was subsequently undertaken. The alpha-galactosidase activity in his serum was low, and a final diagnosis of Anderson-Fabry disease with concomitant multicystic kidney was confirmed by genetic analysis.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the lysosomal enzyme a-galactosidase A (a-GalA). The resulting deficiency in a-GalA activity leads to intra-lysosomal accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organ systems. As a consequence, a multisystem disorder develops, culminating in strokes and progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though monitoring treatment is hampered by a lack of surrogate markers of response. Furthermore, even if signs and symptoms of the disease become manifest in childhood, its diagnosis is often delayed. Biomarkers that predict disease progression and respond relatively quickly to effective therapy may be useful to follow individual patients or groups of patients. Here we report the use of 2 different mass spectrometry-based proteomic techniques to identify disease-associated compositional changes that can be used as early biomarkers of the pathology, as well as for monitoring the effectiveness of ERT. To this purpose, we compared the renal Fabry urinary proteome with normal (control) urine using, respectively, 2-dimensional gel electrophoresis and label-free quantification. Our preliminary results show that the urinary protein pattern of affected patients can be easily distinguished from that of healthy subjects both qualitatively and quantitatively, thus encouraging further studies in the search for FD-specific biomarkers using this proteomic approach.

Renal transplantation is associated with better survival and improved quality of life compared to maintenance dialysis. Although many sleep disorders improve or even disappear after a successful transplantation, sleep quality remains low, and the prevalence of sleep complaints, although lower than in dialysis patients, is much higher than in the general population. Few studies have dealt with sleep problems of renal transplant patients: despite reporting obvious differences in the prevalence of the single sleep disorders, all underline the importance of psychological problems in conditioning sleep. In the diagnosis of sleep disorders, the nephrologist must learn to distinguish medical risk factors (pain, pruritus, tremors, drugs) and psychological aspects (depression, anxiety, fear), since they are potentially modifiable with the appropriate treatment.

Background: A variable inhibition of erythropoiesis has been reported in uremic patients with renal anemia receiving anti-renin-angiotensin-system (RAS) drugs (angiotensin-converting-enzyme inhibitors, and angiotensin-receptor-antagonists). The time to development of renal anemia before dialysis is still unknown., Methods: A retrospective cohort study (1 to 15 years) on records of 327 out-patients (217 males, 110 females) without anemia and with chronic renal insufficiency (creatinine clearance 16 to 75 mL/min) was conducted to estimate the time to development of renal anemia (Hb < 11.5 g/dL in females and Hb < 12.5 g/dL in men), and the time to decrease of Hb by 1 and 2 g/dL or more, irrespective of anemia development. Two treatment groups were analyzed: 142 patients with, and 185 without anti-RAS drugs., Results: Median survival time to development of anemia was 81 months, 59 months to the loss of Hb > 1 g/dL, and 94 months for the loss of Hb > 2 g/dL. Anemia developed significantly earlier in patients with initial Ccr < 40 mL/min and in those with initial Hb < 14 g/dL. In the multivariate analysis (Cox model), male gender, Ccr < 40 mL/min, and Hb < 14 g/dL, in increasing order of relative risk, significantly contributed to prediction of anemia development without any influence of the treatment with anti-RAS drugs. The same results were obtained considering survival to the loss of either Hb > 1 g/dL or Hb > 2 g/dL., Conclusions: Development of renal anemia in mild to severe chronic kidney disease is not influenced by treatment with anti-RAS drugs.

Background: Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of these recommendations in clinical practice is unknown., Methods: We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months., Results: Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%)., Conclusions: BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.