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BACKGROUND Very low-protein intake during chronic kidney disease (CKD) improves metabolic disorders and may delay dialysis start without compromising nutritional status, but concerns have been raised on a possible negative effect on survival during dialysis. This study aimed at evaluating whether a very low-protein diet during CKD is associated with a greater risk of death while on dialysis treatment. METHODS This is an historical, cohort, controlled study, enrolling patients at dialysis start previously treated in a tertiary nephrology clinic with a very low-protein diet supplemented with amino acids and ketoacids (s-VLPD group, n = 184) or without s-VLPD [tertiary nephrology care (TNC) group, n = 334] and unselected patients [control (CON) group, n = 9.092]. The major outcome was survival rate during end-stage renal disease associated to s-VLPD treatment during CKD. The propensity score methods and Cox regression model were used to match groups at the start of dialysis to perform survival analysis and estimate adjusted hazard ratio (HR). RESULTS In s-VLPD, TNC and CON groups, average age was 67.5, 66.0 and 66.3 years, respectively (P = 0.521) and male prevalence was 55, 55 and 62%, respectively (P = 0.004). Diabetes prevalence differed in the three groups (P < 0.001), being 18, 17 and 31% in s-VLPD, CON and TNC, respectively. A different prevalence of cardiovascular (CV) disease was found (P < 0.001), being similar in TNC and CON (31 and 25%) and higher in s-VLPD (41%). Median follow-up during renal replacement therapy (RRT) was 36, 32 and 36 months in the three groups. Adjusted HR estimated on matched propensity patients was 0.59 (0.45-0.78) for s-VLPD versus CON. Subgroup analysis showed a lower mortality risk in s-VLPD versus matched-CON in younger patients (

A 35-year-old woman was admitted to the Nephrology and Dialysis Unit of Pisa University for hypertension, hypokalaemia, renal impairment, proteinuria and hyperglycaemia. plasma renin activity (PRA) and plasma aldosterone were elevated, but Doppler ultrasound and angio-computed tomography (CT) of renal arteries were normal. Abdomen CT revealed only a left adrenal mass, and measurement of catecholamines suggested the diagnosis of pheochromocytoma. Biochemical findings suggestive of hyperparathyroidism were also detected, but a multiple endocrine disorder was excluded by genetic analysis. Pathology examination confirmed the pheochromocytoma and immunohistochemistry also showed positivity for parathyroid hormone. After surgery, disappearance of the symptoms and normalization of all haemodynamic and humoral parameters was observed. This is a rare case of pheochromocytoma responsible for secondary hyperaldosteronism, hyperparathyroidism, proteinuric renal disease and diabetes mellitus.

It is well known that the abnormal accumulation of lipids can occur in kidneys of patients affected by some metabolic disorders due either to inherited enzymatic deficiency or to an acquired lipid alteration as in nephrotic syndrome. Lipoprotein glomerulopathy (LG), briefly described in a patient of Koitabashi in 1987 in a review on renal lipidoses authored by Faraggiana and Churg, represents an emerging novel storage renal disease. This rare and unique nephropathy is characterized by the presence of lipoprotein thrombi in dilated glomerular capillary lumina associated with type III hyperlipoproteinemia, and high serum levels of apolipoprotein E (apo E). Several specific studies conducted by Saito et al on his patients from 1989, revealed that it was an hereditary disease with an autosomal recessive pattern that predominantly affects patients of Asian ancestry, mainly the Japanese population, but which very seldom, can also occur in white subjects. The disorder is probably due to an inherited altered lipid metabolism due to a mutation of the apo E genetic code. Clinically, LG is characterized by proteinuria generally associated with nephrotic syndrome and progressive renal insufficiency. We describe the cases of 2 Italian adult white male patients affected by LG, admitted in our nephrology unit in 2004 and in 2009, respectively.

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Ezetimibe (E) is a new cholesterol adsorption inhibitor which prevents the adsorption of dietary and biliary cholesterol by binding to a recently described cholesterol transporter. This pilot study was performed to evaluate the safety and the low-density lipoprotein (LDL)-C and C-reactive protein lowering efficacy of atorvastatin (A) and of the association of A plus E in five renal transplant patients with hypercholesterolemia and mild renal functional impairment receiving cyclosporine-A (CsA). Patients received for three periods, each of 3 weeks, A at a dose of 20 mg/day; A at a dose of 10 mg/day and finally, A 10 mg plus E 10 mg daily. The medications were well-tolerated and no important clinical or laboratory (muscle enzyme, creatinine clearance and CsA concentration) abnormalities were observed throughout the study period. A alone lead to target LDL-C values only in two of five patients and did not significantly reduce the mean CRP values. The combination of E plus A produced the lowest lipid levels and significantly reduced CRP mean values and allowed all patients to attain target levels of LDL-C: total cholesterol decreased from 240 +/- 42 (mean +/- S.D.) to 171 +/- 34 mg/dl, LDL-C from 129 +/- 32 to 87 +/- 21 mg/dl, plasma triglycerides from 330 +/- 54 to 194 +/- 71 mg/dl and CRP from 6.2 +/- 1.9 to 3.9 +/- 2.4 mg/l (P < 0.05 for all). This pilot study suggests that the co-administration of E and A at 10 mg/day in renal transplant patients receiving CsA is well-tolerated and effective in reducing important cardiovascular risk factors.

Objective Dietary phosphate restriction is one of the means of phosphatemia control in dialysis patients. To limit dietary phosphate intake, appropriate food choices are recommended, but this often creates a conflict with the high-normal protein requirement of dialysis patients. Although food processing by boiling may be a safe tool for eliminating many minerals, this method poses a risk for loss of important nutrients, including proteins. The goal of this study was to assess the effect of boiling on phosphate and protein nitrogen changes in commonly used foods that contain proteins of high biological value. Methods We evaluated the true retention values of dry matter, crude protein, and total phosphorus in fresh beef and chicken breast before and after 10, 20, and 30 minutes of boiling; the reported values represent the average of five determinations. Results Compared with crude raw samples, dry matter retention in cooked beef was reduced up to 92% ± 6%, crude protein retention was reduced up to 87% ± 10%, and phosphorous retention was reduced up to 42% ± 13%; similar data were obtained when boiling the chicken breast, 93% ± 3%, 81% ± 4%, and 63% ± 6%, respectively. Conclusions Our results show that consuming boiled foods can significantly reduce dietary phosphate while preserving protein intake, namely reducing the effective phosphate intake per gram of dietary protein. This can represent additional advice to the patient for limiting the dietary phosphorus load at the same protein intake, leading to a better control of phosphate balance together with a lower risk of protein malnutrition.

Background: Cohort studies have demonstrated an association between C-reactive protein (CRP) and interleukin-6 (IL-6) and all-cause and cardiovascular mortality in end-stage renal disease (ESRD) patients. Interleukin-8 (IL-8) appears to be not only the plasma expression of the acute-phase response but also a direct pathogenetic mediator of the atherosclerotic process. Methods: To evaluate the role of IL-8 in predicting outcome, 76 chronic dialytic patients were prospectively followed for 18 months. At baseline, blood samples were taken for analysis of high-sensitivity CRP, IL-6, IL-8 and other standard laboratory analyses. Results: Median IL-8 was 5.2 mg/l, therefore near half of the patients had IL-8 values within the range of ‘normal limits’. IL-6 and CRP were significantly correlated (r = 0.45, p < 0.001) and a positive correlation was also found between IL-6 and IL-8 (r = 0.39, p < 0.001). The correlation coefficient between IL-6 and CRP was 0.43 (p < 0.001) and 0.50 (p < 0.001) in patients without and with history and/or clinical signs of cardiovascular disease, respectively. After a follow-up of 1.5 years, 8 patients had died from cardiovascular causes and another 7 patients for other reasons; furthermore 9 major nonfatal cardiovascular events were recorded. Stepwise regression analysis showed IL-8 as the strongest independent predictor of all-cause and cardiovascular events (p = 0.0025) even after adjustment for age and dialytic age, followed by IL-6 and CRP (p < 0.01). Conclusion: Despite a small population and a relatively short follow-up period, this study firstly demonstrated that IL-8 is a powerful independent predictive factor for cardiovascular and overall mortality cause in ESRD patients.

Lipoprotein abnormalities and increased oxidized LDL (OxLDL) are often observed in uremia and are reported to play a central role in the development of cardiovascular disease (CVD). Vegan diet, known for its better lipoprotein profile and antioxidant vitamins content, could protect against CVD. Aim of this study was to investigate the influence of vegan diet supplemented with essential amino acids (EAA) and ketoanalogues (VSD) on both traditional and non-traditional cardiovascular risk factors (CVRF).Twenty-nine patients (18 M, 11 F) aged 55 years (range 29-79 years) with advanced chronic renal failure (median sCr: 5.6 mg/dl) on very low protein vegetarian diet (0.3 g/kg/day) supplemented with a mixture of EAA and ketoacids (VSD) and 31 patients (20 M, 11 F) aged 65 years (range 29 - 82 years) on conventional low-protein diet (CD: 0.6 g/kg/day) with a similar renal function (median sCr: 5.2 mg/dl), were investigated for lipids and apolipoprotein parameters (traditional CVRF) as well as for oxidative stress (oxidized LDL, antibodies against OxLDL and thiobarbituric acid-reactive substances (TBARS)), total homocysteine (tHcy), lipoprotein(a) (Lp(a)), albumin and c-reactive protein (CRP) (non-traditional CVRF) including vitamins A, E, B12 and folic acid.Compared to patients on CD, those on VSD showed increased HDL cholesterol levels (p0.005) with a reduction of LDL cholesterol (p0.01) and an increase of apoA1/apoB ratio (p0.02). Among non-traditional CVRF, a mild but significant reduction of OxLDL (p0.05) with lower TBARS concentrations (p0.01) and a significant reduction of total homocysteine (p0.002), Lp(a) (p0.002) and CRP levels (p0.05) were also observed in these patients. Concentrations of vitamin E and A were not different between the two groups while vitamin B12 and folic acid resulted markedly increased in patients on VSD. OxLDL significantly correlated with total and LDL cholesterol, triglycerides and Apo B in CD but not in VSD patients. Patients on CD also showed a significant correlation between urea and CRP. After a multivariate analysis, only urea (p0.001) and OxLDL (p0.006) were associated to a risk of CRP0.3 mg/dl.These results indicate a better lipoprotein profile in patients on vegan diet including non-traditional CVRF. In particular, these patients show a reduced oxidative stress with a reduced acute-phase response (CRP) as compared to patients on conventional diet. We hypothesize that urea, significantly lower in patients on VSD, may account, possibly together with the reduction of other protein breakdown products, for the decreased acute-phase response observed in these patients. Our findings suggest that low-protein diets, and vegan in particular, may exert a beneficial effect on the development of cardiovascular disease in patients with end-stage renal disease (ESRD).

Evidence exists that phosphate retention plays a major role in causing secondary hyperparathyroidism, cardiovascular morbidity, and loss of residual renal function in chronic renal disease patients, and that a subtle elevation in serum phosphate occurs at early stages in the course of renal insufficiency. The implementation of a low-phosphorus, low-protein dietary regimen plays a special role in the conservative management of chronic renal disease patients, for the prevention and correction of secondary hyperparathyroidism and for the renal and cardiovascular protection. However, the success and safety of dietary phosphate restriction largely depends on good compliance with dietary recommendations, which must represent a major goal to be regularly pursued in the clinical practice. To this aim, it is crucial that dietitians expert in renal nutrition give education and personalized dietary advice, with the aim of enhancing the patient's adherence to nutritional prescriptions.

A dietary management program, consisting of the alternation between a vegetarian low-protein diet (VD) and an animal-based conventional low-protein diet (CLPD), aims to increase foods choices and to improve compliance with dietary prescriptions, psychologic aspects, and the quality of life of renal patients. The present study investigates the subjective effects and the practical consequences of this dietary approach in patients with chronic renal failure.Twenty patients (13 men, 7 women, 53 +/- 10 years) with chronic renal failure (creatinine clearance,45 mL/min) were given the possibility to alternate (at their own convenience) the CLPD with the VD. After a follow-up period of 9 +/- 8 months, biochemistries were drawn and a questionnaire was mailed to asses the patients' subjective remarks about the proposed dietary management.Most of the patients (90%) favorably accepted this dietary schedule because it provided more variety, it was less repetitive, and it was more suitable for those leading an active life. In many cases, patients reported that their quality of life and some psychologic problems were improved, as well as the palatability of the diet. On this dietary regimen, monthly demands of starch-made foods can be reduced and, hence, the social and/or individual costs. These features contributed to better compliance with dietary prescriptions. Nutritional parameters did not change significantly, and a decrease in total and low-density lipoprotein cholesterol levels were observed.Our observations suggest that alternating between an animal-based CLPD and a vegetable-based VD can provide a useful dietary management for renal patients, giving them more chances for long-lasting dietary compliance.

In kidney stone patients, high protein intake and calcitriol overproduction are factors leading to hypercalciuria, but there are conflicting reports on the effects of dietary protein on calcitriol production. To investigate the relationships between serum calcitriol, dietary protein intake, and urinary calcium excretion, 33 male idiopathic calcium stone formers (aged 20-60 years), with normal renal function and on unrestricted diet, have been studied. Dietary protein intake was estimated by the protein catabolic rate determination. Abnormally elevated calcitriol levels were found in 16 patients (48.5%) who had similar levels of serum intact parathyroid hormone and phosphate, creatinine clearance, and calcium and phosphate urinary excretion, but lower protein catabolic rate (82+/-16 vs. 97+/-20 g/day, P0.05) than the patients with normal calcitriol levels. The calcitriol to intact parathyroid hormone ratio was higher in hypercalciuric than in normocalciuric patients (2.4+/-1.1 vs. 1.6+/-0.8, P0.05). Calcitriol was positively correlated with plasma calcium (r=0.41, P0.01) and inversely with protein catabolic rate (r=-0.42, P0.01). Protein catabolic rate was positively correlated with creatinine clearance (r=0.69, P0.001) and urinary phosphate excretion (r=0.72, P0.001). No relationship was observed between calcitriol and creatinine clearance. These results confirm the calcitriol overproduction in calcium stone disease and that the high calcitriol to intact parathyroid hormone ratio is the main feature associated with hypercalciuria. Calcitriol serum levels appear to be unrelated to creatinine clearance, whereas there is an inverse relationship with protein catabolic rate. This suggests that low rather than high dietary protein intake may favor the increase of calcitriol synthesis in male calcium stone formers with normal renal function.

In the course of chronic renal failure, low protein-diets allow better control of metabolic disorders and may delay the start of renal replacement therapy (RRT). However, concerns exist that a very low protein diet supplemented with ketoacids (sVLPD) worsens survival after starting RRT. To evaluate whether a prolonged sVLPD regimen may affect all-cause mortality during the following RRT period, we studied time to all-cause death during RRT in patients previously followed in renal clinics either treated with sVLPD (sVLPD group, n=184, age 67±18 yrs) or not (CKD group, n=334, age 66±14 yrs). A Control group including 9,092 patients (age 66±14 yrs) was selected from the Italian dialysis & transplantation registry (RIDT). In sVLPD, CKD and Control groups, the prevalence of an history of cardiovascular disease was 41, 31, 25% and of diabetes was 18%, 31%, 17%, respectively; the median follow-up time in RRT (36, 32, 36 months) did not differ among groups.Cumulative survival was similar in sVLPD and CKD groups (p=0.638), but significantly higher than in the Control group (Long-rank test, 20,62; p

Background: Proteinuria is a risk factor for end-stage renal disease (ESRD). Creatinine clearance (CrCl) is usually used as a marker to monitor the progression of ESRD, while cystatin C (CYST) has also been considered as a marker of renal function. Tumor-associated trypsin inhibitor (TATI) has been shown to be a promising marker of renal function. The aim of this study was to examine the relationship between CrCl, CYST, s2-microglobulin (B2M) and TATI, with glomerular filtration rate (GFR) in patients with different levels of proteinuria. Methods: Seventy-one patients (37 males, 34 females, mean age 53 ± 15 years) were included in the study. GFR was measured by the bladder cumulative method using 99mTc-DTPA. Blood levels of CYST, B2M and TATI were also measured. CrCl and proteinuria were determined by 24-hour urine collection. Statistical analysis was performed with multivariate analysis. Results: The results are expressed as the ratio to GFR of CrCl and reciprocals of CYST (100/CYST), B2M (100/B2M) and TATI (100/TATI). The ratio CrCl/GFR increased from 1.41 in patients with proteinuria 3 g/day. The ratio 100/CYST/GFR was 1.67 and 2.28 (p

Thirst and hyperdipsia of anuric chronic uremics on maintenance hemodialysis and the possible dipsogenic factors were studied. Exaggerated thirst was present in 213 (86%) of the 247 studied patients. It usually started 4-6 h after the end of the dialysis session, persisted during the whole interdialytic period and often disappeared during the subsequent dialysis. Hyperdipsia, as indicated by the high body weight gain (4%) in the interdialytic periods, was present in 33.6% of patients. The highest rate of increase of body weight occurred in the first hours following the end of dialysis sessions. Hypernatremia, potassium depletion, increasing plasma urea levels and elevated plasma angiotensin II levels were considered as the possible dipsogenic factors of a nonpsychic nature. Sodium is certainly of paramount importance for its obliged extracellular position, and when sodium intake is elevated, hypernatremia is very likely the cause of exaggerated thirst and weight gain in patients on hemodialysis. Potassium depletion may cause thirst in animals, but this condition is extremely rare in patients on maintenance hemodialysis, who often accumulate it. In these patients it is, therefore, unlikely that potassium depletion is a dipsogenic factor. Increasing serum urea levels exert an evident dipsogenic effect in anephric rats and urea, when infused into normal volunteers, stimulates thirst. The extracellular urea levels in the interdialytic period are certainly higher than the intracellular ones, as a consequence of its continuous accumulation, and this creates an osmotic gradient with a dipsogenic effect. When this gradient is reversed, following hemodialysis (which removes first the extracellular urea), the dipsogenic effect disappears.(ABSTRACT TRUNCATED AT 250 WORDS)

Resistance to erythropoiesis-stimulating agents (ESAs) is often associated with chronic inflammation. Here, we investigated how anaemia, ESA resistance and the plasma levels of biological markers of inflammation could influence all-cause and cardiovascular disease morbidity and mortality.Seven hundred and fifty-three haemodialysis (HD) patients (mean age 66 ± 14.2 years, mean dialytic age 70 ± 77 months and diabetes 18.8%) were enrolled and followed-up for 36 months. Demographic, clinical and laboratory data, co-morbidity conditions, administered drugs, all-cause mortality and fatal/non-fatal cardiovascular (CV) events were recorded. We measured ESA resistance index, C-reactive protein (CRP) and interleukin-6 (IL-6).Six hundred and fifty-one patients (86.4%) received ESAs. Patients with haemoglobin level11 g/dL (n = 225) showed increased risk of CV [relative risk (RR) 1.415, 95% confidence interval (CI) 1.046-1.914] and overall mortality (RR 1.897, 95% CI 1.423-2.530) versus patients with haemoglobin levels11 g/dL. ESA resistance values categorized into quartiles (Quartile I5.6, Quartile II 5.7-9.6, Quartile III 9.7-15.4 and Quartile IV15.4) correlated with all-cause mortality and fatal/non-fatal CV events (RR 1.97, 95% CI 1.392-2.786; RR 1.619, 95% CI 1.123-2.332, respectively). Furthermore, albumin was significantly reduced versus reference patients and correlated with all-cause mortality and CV events; CRP levels were higher in hyporesponders (Quartile IV) (P0.001) and predicted all-cause mortality and CV events. IL-6 but not CRP was a strong predictor of ESA resistance.ESA responsiveness can be considered a strong prognostic factor in HD patients and seems to be tightly related to protein-energy wasting and inflammation.

Purpose High-resolution sonography (US) with color Doppler imaging (CDI) is a simple, noninvasive, safe and repeatable technique able to highlight the presence of hyperplastic parathyroid glands and changes in their volume, structure, and vascularization during uremia. The primary aim of this study was to assess the diagnostic accuracy of US and the sensitivity for localizing parathyroid glands with a volume ≥ 500 mm(3). The secondary aim was to assess the parameters that define parathyroid glandular perfusion. Materials and methods The diagnostic use of US was assessed in 40 consecutive uremic patients with severe secondary hyperparathyroidism (sHPT) who were receiving maintenance hemodialysis or conservative therapy with a hypoproteic-hypophosphoric diet and had undergone parathyroidectomy. Prior to surgery (99m)TC-sestamibi scintigraphy (SM) was performed in all patients. Results The sensitivity, specificity, positive predictive value and accuracy of US were 74 %, 75 %, 98 %, and 74 %, respectively. The sensitivity for localizing glands with a volume ≥ 500 mm(3) was 90 %. US and SM had a combined sensitivity of 83 %. The vascularization of parathyroid glands became more evident with increasing glandular volume. With CDI, the signs of hypervascularization (i. e. an enlarged feeding artery at the hilum, a peripheral arc of vascularity and/or ray-like endonodular vessels) were present in 77 % of glands with a volume ≥ 500 mm(3). Conclusion The sensitivity of US is higher than that of SM, but it cannot be compared with that of parathyroidectomy (74 vs. 95 %). However, US/CDI is able to characterize glands with different volumes and vascular patterns. Since glandular volume and vascularization are indicative of the severity of sHPT, this study suggests that the main role of US/CDI in the setting of sHPT should be to complete the diagnosis and to evaluate the morphological changes of enlarged glands during uremia in order to define surgical timing, rather than to assess the presurgical location of glands.

BACKGROUND AND AIM Assessment of physical activity level and of energy expenditure is important in the clinical and nutritional care of dialysis patients, but it is not so easy to accomplish. The SenseWear™ Armband (SWA) is a novel multisensory device that is worn on the upper arm and collects a variety of physiologic data related to physical activity. Thus, duration and intensity of physical activity is recorded and expressed as METs (Metabolic Equivalent Task), and energy expenditure is estimated. The aim of our study was to assess interdialytic spontaneous physical activity in stable chronic hemodialysis (HD) patients and the relation to nutritional status and dietary nutrient intake. PATIENTS AND METHODS In 50 stable patients on maintenance hemodialysis treatment and 33 normal subjects (control group), level of spontaneous physical activity and estimated daily energy expenditure was assessed by SWA and related to biochemistry and anthropometry data, bioelectric impedance vector analysis, and energy and nutrient intake information coming from a 3-day food recall. RESULTS In respect to controls, HD patients showed lower mean daily METs value (1.3 ± 0.3 vs. 1.5 ± 0.2, p 3 METs (89 ± 85 vs. 143 ± 104 min/day, p < 0.05), lower number of steps per day (5,584 ± 3,734 vs. 11,735 ± 5,130, p < 0.001), resulting in a lower estimated energy expenditure (2,190 ± 629 vs. 2,462 ± 443 Kcal/day, p < 0.05). 31 out of the 50 HD patients (62%) had a mean daily value < 1.4 METs and hence were defined as sedentary. They differed from the active patients for higher age (63 ± 12 vs. 54 ± 12 y, p < 0.01), lower energy intake (26.1 ± 6.4 vs. 32.4 ± 11.3 Kcal/day, p < 0.05) and lower phase angle (5.5 ± 1.0 vs. 6.3 ± 0.9, p < 0.05). SWA-based estimation of daily energy expenditure was negatively related to age (r = -0.31, p < 0.05), whereas positive relations were observed with BMI (r = 0.51, p < 0.001), phase angle (r = 0.40, p < 0.01), serum phosphate (r = 0.49, p < 0.001) and albumin (r = 0.41, p < 0.01). The mean daily METs values were strongly related to normalized energy intake (r = 0.47, p < 0.001) and also to protein intake (r = 0.33, p < 0.05) and to phase angle (r = 0.38, p < 0.01). Multiple regression analysis showed that energy intake and dietary protein intake were independently related to the intensity of physical activity. CONCLUSION Our findings indicate that poor physical activity is highly prevalent in stable dialysis patients even when free from physical or neurological disabilities or severe comorbid conditions. The level and intensity of physical activity is positively related to body composition and to dietary nutrient intake. This confirms the strong interrelationship between exercise and nutrition, which in turn are associated with survival, rehabilitation and quality of life in dialysis patients.

Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease. In SHPT, the biology of parathyroid cells changes significantly toward diffuse nodular hyperplasia. Currently, diagnosis of SHPT is based on intact parathyroid hormone serum levels and parameters of mineral metabolism. The morphologic diagnosis of SHPT relies on high-resolution ultrasonography with color Doppler imaging. This report describes a maintenance hemodialysis patient with severe SHPT treated using conventional therapy (phosphate binders and oral/intravenous vitamin D or analogues) and the subsequent addition of a calcimimetic. The role of color Doppler ultrasonography in the diagnosis, clinical follow-up, and assessment of therapeutic response of SHPT is discussed. This case suggests that the availability of calcimimetics has changed the natural history of clinical SHPT and may change the therapeutic utility of parathyroidectomy. Use of color Doppler ultrasonography further supports these therapeutic advances, allowing evaluation of the morphologic and vascular changes in hyperplastic parathyroid glands and aiding clinical, pharmacologic, and surgical strategies.

Background: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia. Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species. The aim of this cross-over randomized study was to compare the effects of a vitamin E-coated polysulfone (Vit E PS) membrane and a non-vitamin E-coated polysulfone (PS) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents (ESAs). Methods: After a 1-month run-in period of standard bicarbonate dialysis with a synthetic membrane, 62 patients of both genders, and older than 18 years, dialysis vintage 48 ± 27 months, BMI 22 ± 3 (from 13 different dialysis units) were randomized (A-B or B-A) in a cross-over design to Vit E PS (treatment A) and to PS (treatment B) both for 6 months. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were determined by a sandwich enzyme immunoassay at baseline and every 2 months; red blood cell count, ESA dose and ESA resistance index (ERI) were assessed monthly. Results: Hemoglobin (Hb) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months (p < 0.001) and remained unchanged in the PS group. Although ESA dosage remained stable during the observation periods in both groups, ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months (p < 0.001). No significant variation of ERI was observed in the PS group. A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS group: CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l (p < 0.001) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml (p < 0.05). In the PS group, CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7, and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 (p = n.s.). Conclusions: Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients; in addition, a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements.

This is a cross-sectional, multicenter, controlled study aiming to evaluate changes of actual dietary nutrient intake in 94 stable hemodialysis patients in respect to 52 normal subjects and guideline recommendations, and to assess the prevalence of signs of malnutrition. Energy and nutrients intake assessment was obtained by a three-day period food recall. Anthropometric and biochemical parameters of nutrition, bioelectric impedance vector analysis, and subjective global assessment (SGA) have been performed to assess nutritional status. SGA-B was scored in 5% of the patients. Body mass index20 Kg/m(2), serum albumin35 g/L, nPNA1.0 g/Kg, and phase angle4.0 degrees were detected in 16.3%, 16%, 23%, and 8.0 % of patients, respectively. HD patients showed a lower energy and protein intake in respect to controls, but no difference occurred when normalized per ideal body weight (29.3 +/- 8.4 vs. 29.5 +/- 8.4 Kcal/Kg i.b.w./d and 1.08 +/- 0.35 vs. 1.12 +/- 0.32 Kcal/Kg i.b.w. /d, respectively). Age was the only parameter that inversely correlates with energy (r = -0.35, p0.001) and protein intake (r = -0.34, p0.001). This study shows that in stable dialysis patients, abnormalities of nutritional parameters are less prevalent than expected by analysis of dietary food intake. Age is the best predictor of energy and protein intake in the dialysis patients who ate less than normal people, but no difference emerged when energy and protein intakes were normalized for body weight. These results recall the attention for individual dietetic counseling in HD patients, and also for a critical re-evaluation of their dietary protein and energy requirements.

Background. The effect of cinacalcet on the structural pattern of hyperplastic parathyroid glands was evaluated, using high-resolution colour Doppler (CD) sonography, in haemodialysis patients with severe, inadequately controlled, secondary hyperparathyroidism (sHPT). Methods. Nine patients (6 males, 3 females; mean age ± SD, 55.5 ± 12.6 years) received cinacalcet, with adaptation of existing concomitant therapies. Biochemical parametersandthemorphologyandvascularpatternofhyperplastic parathyroid glands were measured at baseline and every 6 months thereafter, for a follow-up period of 24–30 months. Results. At baseline, 28 hyperplastic glands were identified. Cinacalcet led to a reduction in glandular volume during the course of the study: 68% in glands with a baseline volume

Dietary manipulation, including protein, phosphorus, and sodium restriction, when coupled with the vegetarian nature of the renal diet and ketoacid supplementation can potentially exert a cardiovascular protective effect in chronic renal failure patients by acting on both traditional and nontraditional cardiovascular risk factors. Blood pressure control may be favored by the reduction of sodium intake and by the vegetarian nature of the diet, which is very important also for lowering serum cholesterol and improving plasma lipid profile. The low protein and phosphorus intake has a crucial role for reducing proteinuria and preventing and reversing hyperphosphatemia and secondary hyperparathyroidism, which are major causes of the vascular calcifications, cardiac damage, and mortality risk of uremic patients. The reduction of nitrogenous waste products and lowering of serum PTH levels may also help ameliorate insulin sensitivity and metabolic control in diabetic patients, as well as increase the responsiveness to erythropoietin therapy, thus allowing greater control of anemia. Protein-restricted diets may have also anti-inflammatory and anti-oxidant properties. Thus, putting aside the still debatable effects on the progression of renal disease and the more admitted effects on uremic signs and symptoms, it is possible that a proper nutritional treatment early in the course of renal disease may be useful also to reduce the cardiovascular risk in the renal patient. However, conclusive data cannot yet be drawn because quality studies are lacking in this field; future studies should be planned to assess the effect of renal diets on hard outcomes, as cardiovascular events or mortality.

Although several registries collecting data of patients with kidney diseases exist, only a few specifically collect data relating to renal biopsy. Kidney biopsy has been performed routinely in Pisa since 1977; the aim of this study was to report the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on histological diagnoses during the years 1977 through 2005. During this time, 3,810 kidney biopsies were performed, of which 89.3% were from native (n=3,446) and 10.7% from transplant kidneys. Throughout this period, 5% of renal biopsies were not diagnostic, so in this paper we report data regarding 3,269 native kidney nephropathies.During the years 1977 through 2005, data for renal biopsies were collected on specific registers filled out by clinicians. Information collected in the database included a variety of indicators, such as clinical anamnesis, creatinine clearance, daily proteinuria, hemoglobin levels, blood pressure, height and weight, clinical presentation, and current medications. Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS) and acute nephritic syndrome (ANS). Renal diseases were divided into 4 major categories: primary glomerulonephritis (GN), secondary GN, tubulointerstitial nephropathies (TIN) and vascular nephropathies (VN).From 1977 up to 1987, a mean of 95 +/- 18 renal biopsies/year were performed; this number significantly increased to 185 +/- 22 renal biopsies/year (range 138-200) (p0.001) in the following period (1988-2005). Renal biopsy was more frequently performed in males (59%) compared with females (41%). Of all diseases of the native kidney, primary GN was the most frequent (66%), followed by secondary GN (25.6%), TIN (4.2%) and VN (4.2%). The type of primary GN with the highest frequency was mesangial GN (both IgA and non-IgA) (45.7%), followed by membranous GN (23%), focal segmental glomerulosclerosis (19.8%), minimal change disease (5.3%), crescentic GN (4.2%) and postinfectious GN (2%). In terms of age, renal biopsy was more frequently performed in patients aged 20 to 60 years, and nearly 60% of patients presented a glomerular filtration rate (GFR)60 ml/min at the time of biopsy. The main clinical reason for performing renal biopsy was UA, in all the types of nephropathies.We confirm data that renal diseases are more frequent in men, with the exception of secondary GN. The mean age at diagnosis was 42 years resulting from the tendency not to perform renal biopsies in children and in elderly patients. Renal biopsy was mainly performed in patients with GFR60 ml/min and asymptomatic urinary abnormalities suggesting concern on the part of clinicians regarding glomerular diseases. The tendency to perform renal biopsies has been significantly increasing throughout our follow-up period.

With the aim to investigate microvascular endothelial function in chronic kidney disease (CKD) patients on conservative treatment, skin blood flowmotion (SBF) was explored by spectral Fourier analysis of skin forearm laser Doppler tracing, registered before and following forearm ischemia in 32 III to V stage CKD patients (23 males, mean age: 52+/-12 years), without diabetes or cardiovascular disease, and in 32 age and sex matched healthy subjects. The power spectral density (PSD) of the 0.009-1.6 Hz total spectrum SBF, as well as of five sub-intervals, each of them related to endothelial (0.009-0.02 Hz), sympathetic (0.02-0.06 Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6 Hz) or cardiac (0.6-1.6 Hz) activity, was measured in PU(2)/Hz (PU=perfusion unit; 1 PU=10 mV). Under basal conditions CKD patients and controls did not differ in skin perfusion or in PSD of total spectrum SBF, as well as of each of the five subintervals considered. No substantial difference was also observed in skin post-ischemic hyperemia between patients and controls. A significant post-ischemic increase in the normalized value of endothelial sub-interval was observed in controls (p0.05, GLM ANOVA analysis of variance), but not in CKD patients. A lower per cent increase in absolute PSD value of endothelial sub-interval was also observed in CKD patients compared to controls (185+/-98 % vs 279+/-243 %, p0.05). The post-ischemic per cent increase in absolute PSD of endothelial sub-interval was negatively related to the systolic blood pressure (r=-0.45, p0.01), to the mean arterial blood pressure (r=-0.40, p0.05) and to the PTH serum levels (r=-0.38, p0.05) in CKD patients. The blunted post-ischemic increase of the endothelial SBF sub-interval can be considered an early sign of microvascular endothelial dysfunction in the CKD studied patients. Arterial hypertension seems to be the main factor related to this SBF abnormality, together with the hormonal CKD related abnormalities.

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p

BACKGROUND HFR [double chamber haemodiafiltration (HDF) with reinfusion of regenerated ultrafiltrate] is a novel dialytic method which combines the processes of diffusion, convection and adsorbance. In this technique an adsorbent cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The aim of this multicentre randomized cross-over study was to compare HFR to online HDF in terms of inflammatory and nutritional parameters. METHODS After a 1 month run-in period of standard bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter (SG 8 Plus - high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco, Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4 months was separated by 1 month of HD and the entire length of the study was 10 months. CRP levels were measured by a highly sensitive nephelometric assay (Dade, Behring) with a sensitivity of 0.1 microg/ml. Cytokine concentrations were determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED-Systems, Vienna]. The sensitivity thresholds were < 5 pg/ml for IL-6 and < 8 pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource, USA). All parameters were determined monthly in patients starting a midweek dialytic session. RESULTS Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0 +/- 3.2 to 5.6 +/- 3.4 mg/l with HFR (P < 0.05) and from 9.4 +/- 4.3 to 5.9 +/- 3.9 mg/l with HDF (P < 0.05). IL-6 decreased from 14.8 +/- 6.3 to 10.1 +/- 3.2 with HFR (P < 0.02) and from 12.1 +/- 4.2 to 9.6 +/- 3.7 with HDF (P = ns) with a percentage decrease after 4 months of 32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP increased from 5.7 +/- 3.6 to 8.7 +/- 3.9 mg/l (P < 0.01) and IL-6 from 10 +/- 3.4 to 13.5 +/- 5.2 pg/ml (P < 0.01). A significant increase in IL-10 was detected either in HFR (from 4.8 +/- 2.1 to 6.89 +/- 1.7 pg/ml) and in HDF (from 3.3 +/- 1.7 to 8.95 +/- 4.3 pg/ml; P < 0.05) after 4 months. No significant variation in serum leptin levels were observed during the study. CRP and IL-6 were highly correlated (r = 0.54; P < 0.001) as was serum albumin and prealbumin (r = 0.39; P < 0.001). Serum albumin was negatively correlated with CRP (r = -0.26; P < 0.01) and IL-6 (r = -0.19; P < 0.05); serum prealbumin was correlated with IL-6 (r = 0.37; P < 0.001) and with CRP (r = 0.24; P < 0.01). CONCLUSIONS Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous reinfusion to counteract the chronic inflammatory state of the uraemic patient.

Background. The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients. Methods. Our clinical study has been designed as a randomized double-blind placebo controlled study. A total of 55 chronic kidney disease (CKD) patients at stages 3 and 4 (mean creatinine clearance 45 ml/min, range 15-60) were randomly assigned to receive simvastatin 40 mg/day or placebo, added to their ongoing treatment, for 6 months. Blood samples were obtained at baseline, and after 3 and 6 months of observation for the determination of lipids, inflammatory markers and renal function. For the in vitro studies, the effect of increasing doses of simvastatin on cytokine production [namely interleukin (IL)-6 and IL-8] in human cultured monocytes from 10 healthy subjects (HS) and 15 CKD patients stimulated by lipopolysaccharide (LPS) was investigated. Results. A significant reduction in total cholesterol from 221 ± 44 mg/dl to 184 ± 41 mg/dl (3 months) and to 186 ± 39 mg/dl (6 months) (P < 0.02) and low-density lipoprotein cholesterol from 139 ± 40 mg/dl to 104 ± 29 mg/dl (3 months) and to 100 ±31 mg/dl (6 months) (P < 0.001) was observed in the 28 patients treated with simvastatin. In this group, C-reactive protein (CRP) levels significantly decreased from 2.6 mg/l [interquartile range (IQR 4.9)] to 2.0 mg/l (IQR 1.9) (P= 0.03) at 6 months (P < 0.05). A parallel reduction of IL-6 levels from 5.1 pg/ml (IQR 3.8) to 3.5pg/ml (IQR 3.1) (P=0.001) at 6 months was also observed. No significant reduction in inflammatory markers [CRP from 5.1 mg/l (IQR 1.9) to 5.4mg/l (IQR 1.3) (P=NS) at 6 months] or plasma lipids [LDL-cholesterol from 127 ± 32 mg/dl to 131 ± 21 mg/dl (6 months)] was observed in the 27 patients of the placebo group. In the in vitro studies, the average value for cell-associated IL-6 and IL-8 was higher in CKD (155 ± 95 pg/ml monocytes for IL-6 and 722 ± 921 pg/ml monocytes for IL-8) vs HS (137 ± 87 pg/ml monocytes and 186 ± 125pg/ml monocytes) (P < 0.01) and was not affected by simvastatin alone. LPS resulted in a significant increase in cytokine production (IL-6: 1954 ± 321 pg/ml monocytes for CKD and 1451 ± 237 pg/ml monocytes for HS; P < 0.001); the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups. Conclusions. These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.

Evidence exists that left ventricular function is impaired in chronic uremic patients. During hemodialysis (HD) treatment, myocardium undergoes electrolyte, hemodynamic and neuro-humoral stress; however, data about the acute changes on ventricular function are controversial. Aim of the present study was to evaluate the effect of a single hemodialysis session on left ventricular (LV) systolic and diastolic function using pulsed tissue Doppler imaging (TDI) sampled by echocardiography. The study group included 20 uremic patients (17 males, aged 51+/-13 yrs) on maintenance HD, free from clinically overt cardiac dysfunction who underwent echocardiography with pulsed TDI 30 min prior and 30 min after a HD session. TDI was performed by placing the sample volume in the center of the basal lateral segment and the basal interventricular septum in the apical four-chamber view. Myocardial systolic wave (S(m)) and early (E(m)) and atrial (A(m)) diastolic waves were measured. On standard sonography examination, no significant changes in LV systolic function parameters were observed after HD, but the indices for LV diastolic function deteriorated significantly (peak E, 75.4+/-11.2 vs. 58.8+/-12.5 cm/s, P0.01; E/A ratio, 1.0+/-0.3 vs. 0.8+/-0.2, P0.01). However, regarding TDI measures following HD, the patients exhibited a lower S(m) peak (septum: 7.6+/-1.1 vs. 5.9+/-0.8 cm/s; lateral wall: 7.7+/-1.7 vs. 6.8+/-1.2 cm/s, P0.001), a lower E(m) peak (septum: 8.3+/-1.6 vs. 6.3+/-1.7 cm/s; lateral wall: 10.2+/-2.4 vs. 7.1+/-1.9 cm/s, P0.001), and a reduced E(m)/A(m) ratio (septum: 1.0+/-0.4 vs. 0.7+/-0.2; lateral wall: 1.2+/-0.5 vs. 0.7+/-0.2, P0.001, respectively), as compared to pre-HD parameters. Of interest, peak E(m), and E(m)/A(m) ratio of the lateral wall were negatively related to ultrafiltration rate (r = -0.60, P0.05 and -0.69, P0.01, respectively). Our data indicate that a single hemodialysis session is associated with acute deterioration of diastolic and systolic parameters of myocardial function, as assessed by TDI. These reversible changes could be considered as a cardiac stunning that seems to be related to the ultrafiltration rate and then to the interdialysis weight gain. These findings suggest that low ultrafiltration volume and/or limited interdialytic weight gain are cardioprotective measures in hemodialysis patients.

Patients with chronic renal failure, especially those treated with haemodialysis, have an increased risk of developing atherosclerotic vascular disease probably as a result of enhanced oxidative stress. The human cell membrane possesses electron transfer systems which protect against extracellular pro-oxidant challenge. We evaluated (1) the erythrocyte velocity of ferricyanide reduction (RBC vfcy) in 25 uraemic patients (aged 25-71 years; 14 males), (2) the changes induced by a single haemodialysis session and (3) biomarkers of oxidative stress.Before and after a mid-week dialysis session, we measured RBC vfcy, erythrocyte glutathione (RBC GSH), plasma and red cell membrane malondialdehyde (P and RBC MDA), plasma sulphydryl groups (P SH), plasma vitamin C levels and haemolysis percentage. Pre-dialysis RBC GSH (0.68+/-0.13 vs 0.80+/-0.13 mg/mL, p0.01), P SH (266+/-74 vs 406+/-78 micromol/L, p0.01) and plasma vitamin C (7.0+/-5.1 vs 21.5+/-8.5mg/L, p0.001) were lower than in 25 age-sex-matched healthy controls; P MDA (1.57+/-0.52 vs 0.54+/-0.29 nmol/mL, p0.001), RBC MDA (0.42+/-0.13 vs 0.34+/-0.16 nmol/mL, p0.05) and haemolysis (1.2+/-0.3 vs 0.7+/-0.3%, p0.001) were increased. Baseline RBC vfcy did not differ from normals (13.1+/-5.2 vs 12.9+/-3.2 mmol/mL/h). Following dialysis, RBC vfcy (to 8.9+/-4.5 mmol/mL/h, p0.001) decreased, as well as P MDA, RBC MDA and plasma vitamin C (to 2.5+/-1.4 mg/L, p0.001), whereas P SH groups increased (to 413+/-99 micromol/L, p0.001); haemolysis percentage remained high. RBC vfcy values were correlated to RBC GSH and vitamin C levels.Uraemic patients showed signs of oxidative stress. Pre-dialysis RBC vfcy is maintained in the normal range on account of a reduced intracellular content of GSH and in spite of low plasma ascorbate. A single haemodialysis treatment reduced biomarkers of protein and lipid oxidation but markedly impaired transmembrane electron transfer, which could be explained by acute depletion of electron donors.

Background. Recent investigations have focused on the pathogenetic role of disturbances of calcium phosphate metabolism in causing cardiovascular morbidity and mortality in haemodialysis patients. The aim of the present study was to assess left ventricular function and its relationship to phosphate and calcium plasma levels in stable uraemic patients on haemodialysis treatment. Methods. Twenty uraemic patients (mean age 51 ± 13 years) on maintenance haemodialysis and free from overt cardiac dysfunction, and 20 healthy volunteers underwent standard echocardiography, tissue Doppler-derived early (Em) and late (Am) diastolic velocities, tissue characterization with cyclic variations of integrated backscatter (CV-IBS), and serum biochemistry. Results. With respect to tissue Doppler imaging (TDI), uraemic patients showed a lower Em peak, a higher Am peak, and a reduced Em/Am ratio of both interventricular septum and lateral wall (0.01 > P