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Chronic kidney disease is acknowledged as one of the most relevant disease for public health. Knowledge of epidemiology of CKD may allow public health interventions both for prevention and treatment in order to limit burden and management costs. Nefrodata is a multicentric, prospective, and observational study conducted in Italy, including patients with CKD followed in a specialist setting. The study uses a web-based data setting; it includes 1263 subjects with an estimate glomerular filtration rate (eGFR) less than 60 ml/min *1,73 sqm, followed in outpatient clinics in Italy. Patients' characteristics analysis evidences that old subjects (mean age of 70.3 13.4 years, 55% of them older than 70 years), with cardiovascular morbidity (50,6%) and diabetics (37%) have a high prevalence. With the reduction of residual renal function, prevalence of hyperphospatemia, metabolic acidosis, use of erythropoiesis-stimulating agents, Vitamin D, and diuretics increases. Also allopurinol and gastric-protective drugs are widely used. Fifty-four and eight % of patients with CKD stage 4 and 65.9% of patients with CKD stage 5 received indication on nutritional therapy.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In recent years, many national and international organizations have developed clinical practice guidelines for the most important areas of nephrology. In 1999, the Italian Society of Nephrology (SIN) was one of the first scientific societies to publish (in Giornale Italiano di Nefrologia) the Guidelines for the Treatment of Chronic Renal Failure. Since then, new evidence has accumulated on several aspects of the conservative treatment of chronic kidney disease (CKD). These new data have been included in the present version of the guidelines. The first section of the new guidelines underline the importance of the early detection of CKD and early referral to a nephrologist. The second and third sections are dedicated to the dietetic treatment of chronic renal failure, even when associated with nephrotic syndrome. The fourth section analyzes the anti-hypertensive treatment of renal failure, focusing on the choice of anti-hypertensive drugs to retard the progression of renal failure and reduce cardiovascular mortality. This section highlights the reno-protective role of ACE inhibitors and of AII receptor antagonists in diabetic and nondiabetic nephropathies. The Appendix describes methods for the evaluation of the patient's nutritional status and for protein intake in chronic renal failure.

Aim of this study was to confirm the initial results of a clinical trial on the treatment of Fabry's disease carried out in 13 Italian Nephrology Units. Fabry's disease is a rare, X-linked inherited disease, characterized by a-galactosidase (a-GAL) deficiency, a lysosomial enzymatic activity that results in the accumulation of neutral glycosphingolipids in the endothelial cells of the whole body, and causes painful crises, acroparesthesiae, angiokeratomas, corneal and lens dystrophy, and progressive damage to kidneys, heart and central nervous system, as well as potentially leading to death. The present availability of the recombinant form of a-GAL allows us to prevent or stop the long-term complications of this disease. A clinical trial, generously supported by Genzyme, was started on February 2001. In this trial 20 patients affected by Fabry's disease were periodically treated with agalsidase-beta, the commercial form of the enzyme. The initial results of the trial have indicated that the drug is capable of reducing both the number and intensity of painful crises, improving the patient's sensation of well-being, thus suggesting that this therapeutic approach might theoretically increase life expectancy in these patients.

The relationship between malnutrition and inflammation is by now well established. IL-6 and, probably, other proinflammatory cytokines (mainly IL-1 and TNF) may represent the link between these two entities since these interleukins may promote loss of appetite, muscle protein breakdown and reduced hepatic synthesis of "negative" acute phase proteins like albumin, prealbumin and transferrin. IL-6 also stimulates up to 1000 fold the hepatic synthesis of "positive" acute phase proteins, mainly C-reactive Protein (CRP) and Serum Amyloid A. The association between CRP and cardiovascular mortality in the general population, as well as in haemodialysed uraemic patients, is well established. These crucial interrelationships have modified the interpretation of serum albumin concentration in the diagnosis of malnutrition; a reduced serum albumin concentration, in fact, in the presence of high CRP values should point towards a diagnosis of inflammation, though the inflammation may often induce weight loss or a condition of malnutrition. After switching most patients to a more biocompatible dialysis membrane and improvement of the quality of the dialysis fluid (by adopting hydrophobic filters at the water entry of dialysis devices and bicarbonate powder cartridges) nephrologists have focused their attention on other sources of inflammation (e.g. artificial vascular protheses, presence of infected thrombi, Clamidiae, Helicobacter Pilori, dental granulomas etc.). Starting from these assumptions the diagnosis of malnutrition, once focused mainly on serum albumin reduction, must be based on other parameters (clinical history of body mass wasting, dietary and anthropometric assessment, subjective global assessment, bioimpedance analysis etc.). All these investigations, however, must be examined together to obtain suitable information on the risk of malnutrition in dialysis patients. A comprehensive approach to malnutrition-inflammation in dialysis patients is the object of the present nephrology conference.