Thyroid function in Fabry disease before and after enzyme replacement therapy.

UNLABELLED: AM: Patients with Fabry disease (FD), a genetic disorder caused by lysosomal a-galactosidase-A enzyme deficiency and characterized by a systemic accumulation of globotriaosylceramides, present high prevalence of subclinical hypothyroidism. The pathogenic mechanism is thought not to be related to anti-thyroid autoimmunity and may be dependent by intra-thyroid lipid accumulation. In this study, it was investigated whether thyroid function recovers in FD after long-term enzyme replacement therapy (ERT). METHODS: Study population included 14 FD patients (7 females, 7 males, aged 21-62 years) and 14 sex- and age-matched normal subjects. Thyroid function was evaluated in each patient at baseline and after the beginning of ERT with rh-a-galactosidase-A (1 mg/kg/BW every 2 weeks) for three years. RESULTS: TSH levels were higher in FD patients than in controls (P<0.05). In FD patients, TSH levels were higher before than after ERT (1.9±0.2 vs 1.2±0.2 mU/L, P<0.01) while fT3 and fT4 levels were normal at baseline and unchanged after ERT. At baseline, TSH levels were >3 mU/L in three patients and normalize after ERT. Anti-Tg and/or anti-TPO titres were positive in 14% of patients and 21% of controls. After ERT, the rate of autoimmunity was unchanged. At the thyroid ultrasonography, a slight hypoechoic pattern was found in 71% of patients at baseline and decreased to 43% after ERT. CONCLUSION: Primary hypothyroidism in FD patients is reverted after long-term ERT. A screening of thyroid function and periodical re-evaluation during ERT is mandatory in all FD patients.

[Epidemiology of cardiovascular disease in CKD-MBD]. / Epidemiologia della patologia cardiovascolare nella CKD-MBD.

Evidence has been accumulating in recent years that chronic kidney disease (CKD) is a common disease associated with a high risk of morbidity and mortality. Cardiovascular complications are the leading cause of death in patients with CKD, and the risk of cardiovascular mortality is 10-30-fold higher in dialysis patients than in age-, gender- and race-matched controls. On the basis of this evidence it has been suggested that the cardiovascular risk profile of CKD patients is different from that of the general population, resulting from a complex and peculiar interaction of risk factors. In fact, traditional risk factors such as hypertension, aging, smoking, diabetes, and lipid disorders do not fully explain the high frequency of cardiovascular disease in CKD, so other factors must be involved in the high mortality rate in uremic patients. In this article we will provide an overview of the epidemiology of the cardiovascular risk factors in CKD. Among the non-traditional risk factors we have focused particularly on those related to mineral metabolism, which contribute the high rates of cardiovascular events observed in CKD.

[Renal involvement in Fabry's disease: diagnosis, follow-up and enzyme replacement therapy]. / La nefropatia in corso di malattia di Fabry: diagnosi, follow-up e terapia enzimatica sostitutiva.

Renal involvement in Fabry's disease in males starts at an early age with microalbuminuria and proteinuria and progresses rapidly towards end-stage renal disease requiring dialysis or renal transplantation. Renal involvement, together with cardiac and cerebral damage, is responsible for the severe morbidity and mortality in patients with Fabry's disease. In heterozygous female patients renal involvement has also been documented, but the onset of renal damage occurs later and the progression to end-stage renal disease is slower. Considering the relevance of renal damage in the prognosis of Fabry's disease, it is mandatory to point out the diagnostic criteria of Fabry's nephropathy and the modalities of follow-up of patients with renal involvement. The aim of this study is also to provide recommendations regarding the diagnosis, follow-up and indication for enzyme replacement therapy in patients with Fabry's disease.

ESPEN Guidelines on Parenteral Nutrition: adult renal failure.

Among patients with renal failure, those with ARF and critical illness represent by far the largest group undergoing artificial nutrition. ARF, especially in the ICU, seldom occurs as isolated organ failure but rather is a component of a much more complex metabolic environment, in the setting of the multiple organ failure. Nutritional programs for ARF patients must consider not only the metabolic derangements peculiar to renal failure and with the underlying disease process/associated complications, but also the relevant derangements in nutrient balance due to renal replacement therapies, especially when highly efficient renal replacement therapies (RRT) are used, such as continuous veno-venous hemofiltration (CVVH), or prolonged intermittent modalities such as sustained low-efficiency dialysis (SLED). Finally it is to be taken into account that nutrient requirements can change considerably during the course of illness itself (see also guidelines on PN in intensive care). From a metabolic point of view, patients with CKD or on chronic HD who develop a superimposed acute illness should be considered to be similar to patients with ARF. The same principles in respect of PN should therefore be applied.

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.

[The usefulness of Cochrane systematic reviews in nephrology]. / Le principali revisioni sistematiche Cochrane all'attenzione della Societa' Italiana di Nefrologia: a cosa servono?

Systematic reviews (SRs) of the literature are clinical research studies carried out according to rigorous methodological criteria. They are aimed at searching, critically appraising and summarizing all studies with similar characteristics that address the same research question. The Cochrane Collaboration is the main institution that coordinates the production of SRs. The Cochrane Renal Group is one of the 50 research groups of the Cochrane Collaboration and is in charge of SRs in nephrology. This group compiled the Renal Health Library, an annually updated collection of SRs (Cochrane and not) and randomized controlled trials in nephrology, dialysis and renal transplantation. We searched the Renal Health Library to identify SRs useful to answer clinical questions in patients with renal disease and/or following kidney transplant. The SRs identified were summarized and the results were expressed as relative risk, weighted mean difference, standardized mean difference, and 95% confidence intervals. Since the number of randomized controlled trials is quite large and SRs are a reliable summary of the scientific evidence, their distribution is of paramount importance. Here we show several clinical cases where related SRs in the Renal Health Library provide useful guidance for treatment.

Cardiac performance during exercise in patients with Fabry's disease.

BACKGROUND: Fatigability and dyspnoea on effort are present in many patients with Fabry's disease. We assessed the determinants of cardiac performance during exercise in patients with Fabry's disease and preserved left ventricular ejection fraction at rest. MATERIALS AND METHODS: Sixteen patients with Fabry's disease and 16 control subjects underwent radionuclide angiography at rest and during exercise, tissue Doppler echocardiography and magnetic resonance imaging at rest. RESULTS: The exercise-induced change in stroke volume was +25 +/- 14% in controls and +5.8 +/- 19% in patients with Fabry's disease (P < 0.001). In 10 patients (group 1), the stroke volume increased (+19 +/- 10%), and in 6 patients (group 2) it decreased (-16 +/- 9%) with exercise. Patients of group 2 were older, had worse renal function, higher left ventricular mass and impaired diastolic function compared to group 1. The abnormal stroke volume response to exercise in group 2 was associated with a decrease in end-diastolic volume (P < 0.001) and a lack of reduction of end-systolic volume (P < 0.01) compared with both controls and group 1. The ratio of peak early-diastolic velocity from mitral filling to peak early-diastolic mitral annulus velocity was the only independent predictor of exercise-induced change in stroke volume (B -0.44; SE 0.119; beta-0.70; P < 0.005). CONCLUSIONS: The majority of patients with Fabry's disease were able to augment stroke volume during exercise by increasing end-diastolic volume, whereas patients with more advanced cardiac involvement may experience the inability to increase cardiac output by the Frank Starling mechanism.

[Altered calcium-phosphorus metabolism and low-protein diet]. / Alterazione del metabolismo calcio-fosforo e dieta ipoproteica.

Many metabolic disorders associated with uremia can affect the long-term survival of patients with chronic kidney disease. Such disorders can be defined as: hypocalcemia, increased levels of phosphorus, reduced synthesis of 1,25-dihydroxyvitamin D and serum calcitriol, and reduced expression of vitamin D receptors on parathyroid cells with increased parathyroid hormone levels and secondary hyperparathyroidism. Phosphorus, which plays a crucial role in the progression of progressive renal disease, has been shown to be an independent risk factor for death in hemodialysis patients. Thus, reducing the phosphorus intake by decreasing dietary proteins may slow the progression of renal disease. Hypocalcemia is typically associated with chronic kidney disease. It is due to the reduced intestinal absorption of calcium and the spontaneously reduced protein intake that occur in patients with progressive renal disorders. Activated vitamin D and calcium supplements should be administered to patients who are following low-protein diets to prevent secondary hyperparathyroidism; the doses should be correlated with actual renal function and protein intake.

[Relationship between low-protein diet and hypertension control]. / Rapporto tra dieta ipoproteica e controllo dell'ipertensione arteriosa.

Arterial hypertension is found in almost all patients with chronic kidney disease. The US Kidney Foundation guidelines recommend a pressure target for chronic kidney disease patients (130/80 mmHg) that may be difficult to reach because of the reduced sodium excretion in these patients and the widespread use of vasodilator drugs. Reducing the dietary protein intake may help to lower the dietary sodium load. The 130/80 mmHg target has been reached in 30% of stage 4 and 5 patients only after six months of a very low-protein diet supplemented with keto-analogues and essential amino acids. However, even moderate reductions of dietary sodium intake are useful in patients with compromised renal function, as was shown by Koomans et al more than 20 years ago. Blood pressure levels are lower in vegetarians, possibly also because of the reduced sodium content of potassium-rich vegetarian diets. Diets rich in unrefined cereals, vegetables, fruit and low-fat cheese may be useful in patients with chronic kidney disease. Commercial low-protein preparations may help to design diets that are both low in sodium, potassium and phosphorus and adequate for caloric needs.

[Low-protein dietary therapy in patients with chronic kidney disease]. / Terapia dietetica ipoproteica del paziente con IRC.

Several prospective studies and meta-analyses including the recent Cochrane meta-analysis have demonstrated that reducing the protein content in the diet delays renal death and the start of dialysis in patients with chronic kidney disease (CKD). Reducing the dietary protein intake offers other benefits such as lowering accumulation of uremic toxins and circulating phosphates and improving symptoms and metabolic derangements. Following the publication of the Cochrane meta-analysis, some of the most renowned experts in Italy on dietary therapy in the CKD patient established a working group within the Italian Society of Nephrology (SIN), the ''Nephrontieres'' project. The current supplement of GIN presents the views of the members of the ''Nephrontieres'' group on a range of issues related to dietary therapy in CKD. A CME program for Italian nephrologists also originated from the collaborative work of the group.

[Low-protein diet in Italy today: the conclusions of the Working Group from the Italian Society of Nephrology]. / La dieta ipoproteica oggi in Italia: le conclusioni del Gruppo di Lavoro SIN.

The high estimated prevalence of chronic kidney disease (CKD) forcefully supports the need for collaboration among nephrologists, cardiologists, diabetologists and general practitioners, to reduce the cardiovascular risk of CKD patients and delay the start of dialysis. Many studies confirm that reducing the dietary intake of proteins improves uremia as well as acid-base and phosphorus disorders without exposing the CKD patient to the risk of malnutrition. The possibility of delaying renal death and the start of dialysis by almost one to two years is also recognized, thanks in part to the antiproteinuric effect of low-protein diets supplemented with keto acids and essential amino acids. Reducing the dietary protein intake delays the start of dialysis independently of the effect of renin-angiotensin system (RAS)-active antihypertensive drugs. Reduction of the dietary protein intake is indicated in patients with a glomerular filtration rate <25 mL/min (CKD stages 4 and 5). Some situations may, however, require an earlier switch to a low-protein diet, e.g., high proteinuria, renal function worsening at more than 5 mL/min/year, diabetes, and metabolic decompensation. If well designed and properly carried out, reduction of the dietary intake of proteins is not associated with low serum albumin levels or malnutrition, and does not affect patients death. Today, highly palatable, high-quality reduced protein preparations are widely available to reduce the protein intake of CKD patients.

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.

[Antihypertensive agents for the prevention of chronic kidney disease progression: guideline from the Italian Society of Nephrology]. / Farmaci antipertensivi per la prevenzione della progressione delle nefropatie croniche: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the use of antihypertensive agents to prevent chronic kidney disease progression (CKD) is presented. METHODS: SR of RCT and RCT on antihypertensive agents used to prevent CKD progression were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Seven SR and 26 further RCT were found addressing this intervention issue. Methodological quality of available RCT was suboptimal according to current methodological standards. Angiotensin converting enzyme inhibitors (ACE-I) are associated with significant effects on the prevention of CKD progression in non-diabetic and diabetic patients (evidence from SR). Angiotensin receptor blockers (ARB) are as effective as ACE-I in delaying CKD progression in diabetic and non-diabetic patients (evidence from SR). Dihydropyridine and non-dihydropyridine calcium antagonists have not been found to significantly affect proteinuria and CKD progression (evidence from SR). Combination therapy with ACE-I and ARB is associated with a significant reduction in the risk of CKD progression and proteinuria, but long term data are only available in patients with non-diabetic nephropathy (evidence from RCT). CONCLUSION: Available evidence of renal protection suggest that ACE-I and ARB should be recommended in CKD patients (diabetic and non-diabetic nephropathy). Further studies are necessary to test the effectiveness of other antihypertensive agents or combination therapy.

[Erythropoietins and haemoglobin targets to prevent the progression of chronic kidney disease: guideline from the Italian Society of Nephrology]. / Utilizzo di eritropoietina e targets di emoglobina e progressione del danno renale: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of Systematic Reviews (SR) of Randomized Trials (RCT) or RCT data only. The present guideline reports evidence of the use of Erythropoietins (EPO) and/or optimal haemoglobin (Hgb) targets to delay Chronic Kidney Disease (CKD) progression. METHODS: SR of RCT and RCT on EPO and different Hgb targets in CKD (pre-dialysis) were identified searching in the Cochrane Library and Renal Health Library (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Two SR (15 RCT) and 5 further RCT were found addressing the intervention issue. No significant evidence supporting the use of EPO compared with placebo/no treatment to prevent or delay CKD progression was found (evidence from SR). Progression rates do not appear to be affected by Hgb targets (evidence from SR). Methodological quality of included RCT was suboptimal. In diabetic patients not receiving renin-angiotensin-system inhibitors, early EPO treatment (when Hgb ≥9 g/dL) with target Hgb ≥13 g/dL as compared to delayed treatment initiation (Hgb < 9 g/dL) is associated with reduced risk of disease progression, end-stage renal disease and death (evidence from RCT). CONCLUSION: In CKD patients not undergoing dialysis current evidence does not support the hypothesis that EPO treatment or optimal Hgb targets reduce the progression rate of the disease. Further studies are necessary to test this hypothesis in selected patient populations.

[Use of statins for preventing cardiovascular and renal outcomes in patients with chronic kidney disease excluding dialysis: guideline from the Italian Society of Nephrology]. / Statine per la prevenzione della progressione del danno renale: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the efficacy of statins in chronic kidney disease patients (CKD, non-dialysis patients) is presented. METHODS: SR of RCT and RCT on statins in CKD (non-dialysis) patients were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Three SR and 36 RCT were found addressing this intervention issue. Methodological quality of the relevant RCT was suboptimal. There is no enough evidence to suggest that statins are associated with a significant reduction in the risk of serum creatinine doubling or of end-stage renal disease in CKD patients (evidence from SR and RCT). Statins compared to placebo or no treatment are associated with significant improvements in proteinuria (evidence from SR). Statins are also associated with significant reduction in the risk of cardiovascular events and mortality in CKD patients (evidence from SR and RCT) and in renal transplant recipients (evidence from RCT), and no significant increases in the risk of rhabdomyolysis and hepatotoxicity in CKD patients. CONCLUSION: Available evidence supports the hypothesis that statins should be recommended in CKD patients (non-dialysis patients) on the basis of significant evidence of cardiac and renal protection and no evidence of significant harms. Further studies are necessary to test this hypothesis in selected patient populations.

Endocrine dysfunction in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is a genetic disorder caused by lysosomal alpha-galactosidase-A deficiency and is characterized by the systemic accumulation of globotriaosylceramide. All endocrine glands are susceptible to globotriaosylceramide accumulation because of their high vascularization and low cellular proliferation rate. Nevertheless, this endocrine system has never been investigated in detail. OBJECTIVE: We aimed to investigate the function and morphology of the endocrine glands in FD. PATIENTS: The thyroid, gonadal, adrenal, and GH/IGF-I axes were evaluated in 18 FD patients (nine females and nine males, aged 21-64 yr) and 18 sex- and age-matched healthy subjects. STUDY DESIGN: We conducted an observational, analytical, open, prospective study. INTERVENTIONS: Ten of the 18 patients received enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase-A (agalsidase beta) at a dose of 1 mg/kg body weight every 2 wk. RESULTS: FD patients had higher baseline TSH levels than controls (P < 0.01). Three subjects were diagnosed with an early stage of subclinical primary hypothyroidism associated with negative antithyroid antibodies. A history of menses abnormalities, miscarriage, or assisted delivery was found in 89% of FD women. Asthenozoospermia, oligozoospermia, or both were found in all FD men through seminal fluid analysis. FD patients had significantly higher circulating ACTH and lower cortisol levels than controls (P < 0.05). In patients under ERT, a suboptimal cortisol response to the 250-microg ACTH test was found in 10%, and the ACTH-stimulated cortisol peak was significantly correlated to the health status profile (P < 0.05). CONCLUSION: A variety of latent endocrine dysfunctions, including life-threatening conditions, occur in patients with FD. Endocrine dysfunctions are also present in patients already receiving ERT and are in part related to their persistent poor quality of life. An endocrine work-up should be recommended in all FD patients. Adequate monitoring and hormonal therapy, when required, have to be performed in cases of subclinical endocrine dysfunction to avoid life-threatening events.

[The Italian Society of Nephrology Guidelines (3rd Edition): principles and methods]. / I principi ed i metodi della III edizione delle Linee Guida della Società Italiana di Nefrologia (2005-2006).

Scientific Societies at both a local and international level are making big effort to prepare their clinical practice guidelines. The Italian Society of Nephrology has already published in two previous editions a series of guidelines relating to various aspects of management and diagnosis of different renal diseases. In this review we present the criteria of the 3(rd) edition of the Italian Society of Nephrology guidelines. This 3(rd) edition of guidelines will be based on the availability of scientific evidence in different areas of nephrology, dialysis and transplantation. Ten key intervention questions have been identified, based on the availability of systematic reviews of randomized trials or individual randomized address them. Systematic reviews and randomized trials are the optimal study design to address intervention questions. These have been summarized based upon rigid methodological criteria and strictly reflect the evidence basis. The different phases of development and publication of the 3(rd) edition of the Italian Society of Nephrology guidelines are presented.

[Fabry nephropathy in a female with superposed IgA glomerulonephritis]. / Nefropatia da malattia di Fabry in donna eterozigote con sovraimposta glomerulonefrite da IgA.

BACKGROUND: In Anderson-Fabry disease (AFd), the kidney is affected in all hemizygous males and in some heterozygous females. Female carriers can present subtle renal abnormalities due to glycosphingolipid (GSL) accumulation within renal cells. Renal biopsy is rarely performed in female Fabry patients because clinical renal manifestations are usually lacking. However, female carriers can accumulate GSL in their renal cells despite the absence of clinically evident kidney disease. CASE REPORT: We performed a kidney biopsy in a 52-year-old female patient, a Fabry disease carrier. The patient showed normal glomerular filtration rate, persistent microhematuria and proteinuria (about 1.7 g/24 hr), cornea "verticillata", and evident left ventricular hypertrophy. The molecular study documented a missense mutation R227Q in exon 5 of the alpha-galactosidase A gene. Optical microscopy showed electron-dense mesangial deposits due IgA glomerulonephritis, as confirmed by immunofluorescence. We decided to start therapy with angiotensin-converting enzyme inhibitors (ACE-I). After 8 months of treatment, the patient demonstrated proteinuria of 0.9 g/24 hr. To decide when to start treatment using enzyme replacement therapy (ERT) with human recombinant GAL A (Fabrazyme), we decided to perform an electron microscopy study of the renal biopsy. The renal ultrastructural findings were typical GSL inclusions in all kinds of glomerular cells, in tubular epithelial cells and in endothelial cells of interstitial capillaries, confirming the hypothesis of Fabry nephropathy. Consequently, Fabrazyme was given at a standard dose of 1 mg/kg every 2 weeks. After 24 months of combined treatment (ACE-I-Fabrazyme), proteinuria decreased to 0.2 g/24 hr. CONCLUSIONS: The importance of performing the ultrastructural examination of the kidney biopsy is stressed, especially in heterozygous Fabry patients to evaluate the need to treat them with ERT and to evaluate the degree of renal involvement.

Management of hypertension in chronic kidney disease: the Italian multicentric study.

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.

Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry's disease.

Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness.