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The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

BACKGROUND: Recent studies have indicated that the implementation of international guidelines for the management of renal patients is suboptimal in Italy. The Italian Society of Nephrology (SIN) decided to undertake a multicentre study to obtain a clear picture of clinical policies on chronic kidney disease (CKD) in Italy. METHODS: A 76-item structured questionnaire, designed to evaluate the organization of clinical care, was administered to the director of each participating centre, within the context of a large observational trial in 100 Italian nephrology centres, collecting information on newly diagnosed CKD patients (K/DOQI stage 3-5) on conservative treatment. This paper reports the questionnaire results related to management of anaemia and bone metabolism disorders; assessment of renal function; creation of a vascular access for dialysis and referral of patients to a nephrologist. RESULTS: Clinical policies at the centre level deviated from guideline recommendations in 70% (timing of vascular access creation) to 25% (assessment of iron deficiency) of centres. Assessment of renal function differed from the recommended approach in 30% of centres; clinical policies related to anaemia and bone disease did not coincide with guideline standards in 50 and 40% of centres, respectively. Directors of renal unit estimates indicate that the creation of a vascular access occurs very late in 38% of patients and that referral to a nephrologist is late in approximately 40% of cases. CONCLUSION: This survey in Italy highlights important deviations of clinical policies at the centre level from guideline recommendations.

Nowadays, there is a renewed interest in bone changes in experimental and clinical nephrology. However, the need for understanding the peculiarity of bone can be traced back to the 5th century BC, when Empedocles of Acragas put forward a theory of a world made of air, water, fire, and earth governed by love and hate. By observing the various body tissues, he strove to demonstrate that they consisted of 4 elements assembled with different mathematical ratios (logos). Blood is considered the most perfect tissue, because the ratio between elements is one. Bone is a very unusual tissue because it is made of 2 parts of earth, 2 parts of water, and 4 parts of fire. This kind of reasoning could be considered the first cry in the birth of quantitative chemistry. Nowadays, there is a renewed interest in bone changes in experimental and clinical nephrology. However, the need for understanding the peculiarity of bone can be traced back to the 5th century BC, when Empedocles of Acragas put forward a theory of a world made of air, water, fire, and earth governed by love and hate. By observing the various body tissues, he strove to demonstrate that they consisted of 4 elements assembled with different mathematical ratios (logos). Blood is considered the most perfect tissue, because the ratio between elements is one. Bone is a very unusual tissue because it is made of 2 parts of earth, 2 parts of water, and 4 parts of fire. This kind of reasoning could be considered the first cry in the birth of quantitative chemistry.

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-dietlyl-enetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR > 100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTcDTPA, respectively. In patients with GFR < 25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.

Background and aims The prognostic role of LDL in non-dialysis chronic kidney disease (CKD) is still undefined. We addressed this question in a multicenter prospective study including patients referred to nephrologist for management. Methods and results 1306 patients with CKD stage III–V were studied at basal visit in 79 Italian nephrology clinics in 2004–2006, and then followed for survival analyses. Study endpoints were incident cardiovascular -CV events (fatal and major non-fatal) and renal events (start of renal replacement therapy or eGFR halving). Mean age was 67.6 ± 11.8 years, male 65%, diabetes 25%, CV disease 27%, and eGFR 35.8 ± 12.5 mL/min/1.73 m 2 . LDL was 119 ± 40 mg/dL, with high levels in 50.1% and 82.8% defined on the basis of the individual CV risk profile estimated according to ATPIII 2001 and ESC 2012 guidelines (LDL 100 to 160, and >70 or >100 mg/dL, respectively). Over a median follow up of 2.87 years, 178 CV and 181 renal events occurred. At multivariable Cox analyses, CV risk linearly increased with higher LDL (hazard ratio-HR per 40 mg/dL higher LDL: 1.20, 95% confidence intervals-CI 1.03–1.39); risk doubled when considering high LDL defined according to ESC 2012 (HR 2.37, 95%CI 1.39–4.03) while this association was not significant when considering the higher threshold levels of ATPIII 2001 (HR 1.10, 95%CI 0.82–1.49). No association emerged between LDL and renal risk. Conclusion In non-dialysis CKD patients, CV risk increases linearly with higher LDL and is more than doubled when considering the lower threshold values currently indicated for defining optimal LDL level.

Background: Urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) have been used separately to provide information about cardiovascular risk. We analyzed whether UAE and eGFR used together provide complementary information. Methods: We analyzed UAE, eGFR, cardiovascular risk factors, and incidence of cardiovascular disease in 1665men and women of the Gubbio Population Study (aged 45-64 years). We designated UAE in the highest decile as high (18.6 μg/min in men and15.7 μg/min in women) and eGFR in the lowest decile as low (64.20 mL/min/1.73m2 in men and 57.90 mL/min/1.73 m2 in women). Results: Kidney dysfunction defined using both markers was more frequent than using 1 marker (UAE alone or eGFR alone) (P.001) because high UAE and low eGFR clustered in different individuals and were weakly associated with each other (P=.12). The hazard ratio (HR) for incident cardiovascular disease was elevated for both markers, independently of each other (HR for high UAE, 2.15; 95% confidence interval [CI], 1.33-3.49; HR for low eGFR, 2.14; 95% CI, 1.32-3.48). Kidney dysfunction defined by both markers predicted cardiovascular disease independently of sex, age, hypertension, hypercholesterolemia, smoking, diabetes mellitus, prior cardiovascular disease, left ventricular hypertrophy, and obesity (HR, 1.50; 95% CI, 1.05-2.14). The discriminant power of dysfunction defined by both markers was statistically significant (area under the receiver operating characteristic curve, 0.569 [P=.02]) and slightly higher than what was found with 1 marker of diabetes mellitus, prior cardiovascular disease, left ventricular hypertrophy, and obesity. Conclusions: High UAE and low eGFR provide complementary information in defining kidney dysfunction because they cluster in different individuals. Concomitant evaluation of both markers should be considered to adequately assess kidney dysfunction and cardiovascular risk.

Patients with advanced heart failure commonly develop simple or mixed acid-base disturbances. The altered acid-base homeostasis can occur as a consequence of the heart failure itself, the therapeutic interventions, or associated conditions. The present study examined acid-base disorders in patients with heart failure who received successful heart transplantation. The information collected should provide light on the determinants of acid-base disorders in this patient population. Seventy status 2 UNOS (United Network Organ Sharing) patients listed for heart transplantation were enrolled in this study. All patients received loop diuretics, spironolactone, ACE inhibitors, carvedilol and digitalis as needed. Patients were studied again at discharge after transplantation, under cyclosporine, azathioprine, steroids, loop diuretics and ACE inhibitors. After heart transplantation, a significant increase of ejection fraction from 19.7 ± 0.63 to 53.6 ± 0.9% (p < 0.0001) occurred along with a concomitant reduction of central venous pressure (p < 0.0001) from 12.6 ± 0.20 to 6.9 ± 0.21 mm Hg. Before heart transplantation there was high-normal pH (7.43 ± 0.009), slight loss of hydrogen ions (35.4 ± 0.4 nmol/l), slightly reduced pCO2 (37.6 ± 1.1 mm Hg). After heart transplantation a stability of blood pH and hydrogen ion concentrations was found but bicarbonate increased significantly (p < 0.02) from 24.2 ± 0.61 to 26.2 ± 0.51 mmol/l and pCO2 from 37.6 ± 1.1 to 39.3 ± 0.7 mm Hg (p < 0.05). Plasma renin activity averaged 3.80 ± 0.6 pg/ml before heart transplantation and 2.82 ± 0.4 pg/ml after (p < 0.01). Aldosterone concentration averaged 380 ±15 pg/ml before heart transplantation and 280 ± 10 pg/ml after (p < 0.01). These data suggest that in patients before heart transplantation there is a mixed acid-base imbalance that includes respiratory alkalosis and metabolic alkalosis. After transplantation the recovery of the abnormal circulatory status erased the initial respiratory alkalosis but metabolic alkalosis persisted and accounted for a further rise in plasma bicarbonate.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting. Copyright © 2001 by W.B. Saunders Company.

The long-term risk of end-stage renal disease is high in persons with isolated systolic hypertension, that is, those with an elevation of pulse pressure and not of diastolic pressure. Other data suggest that pulse pressure is a predictor of the hypertension-induced organ damage. Microalbuminuria is considered an early sign of glomerular damage caused by hypertension. The study shows the relationship of pulse pressure and isolated systolic hypertension to microalbuminuria in nondiabetic subjects.This is a cross sectional analysis for a population sample of 677 men and 890 women, aged 45 to 64 years, who were without diabetes mellitus and macroalbuminuria. Data collection included: overnight urinary albumin and creatinine excretion; fasting plasma glucose, cholesterol, and creatinine; creatinine clearance; and blood pressure, weight, height, medical history, and smoking habit. Pulse pressure was calculated as systolic minus diastolic pressure. Isolated systolic hypertension was defined as systolic pressureor =140 mm Hg in persons not on antihypertensive drugs and with diastolic pressure90 mm Hg. Microalbuminuria was defined as urinary albumin excretionor =20 microg/min.Pulse pressure and isolated systolic hypertension were significantly related to urinary albumin excretion and the prevalence of microalbuminuria in univariate and multivariate analyses. Controlling for gender and other variables, the risk of microalbuminuria was 1.71 with a 15 mm Hg higher pulse pressure (95% CI, 1.31 to 2.22) and 4.95 in the presence of isolated systolic hypertension (95% CI, 3.15 to 7.76).In nondiabetic, middle-aged adults, pulse pressure and isolated systolic hypertension are directly related to microalbuminuria, independent of diastolic pressure and other correlates.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p

Dialysis for octogenarian and nonagenarian patients has increased dramatically in recent decades. Worldwide Registries of dialysis and transplantations show how the incidence rate of patients older than 80 years of age is almost doubled. This increase is probably due to liberalisation of acceptance criteria for dialysis, together with the ageing population. In recent years, the Sicilian and Campanian Registries of dialysis and transplantations have also observed a progressive increase in the elderly population. In order to study survival in this class of patients, we performed a study on a sample of Sicilian and Campanian patients. Regarding Sicilian patients, we considered a sample of 497 patients and grouped them into 3 categories of risk: in the first group (low risk) patients included were70 years old without any co-morbidities; in the second group (average risk), we selected patients between 70 and 80 years old with one or more co-morbidities: in the third group (high risk patients), we included patients aged more than 80 years or with a high number of co-morbidities. The probabilities of survival in the low risk patients after 48 months of treatment was 96.1%; this probability fell to 82.9% for patients included in the high risk group; while the probability of survival for average risk patients was 91.7%. Given the high risk presented by older patients, we focused the second part of our analysis only on octogenarians, studying both Sicilian and Campanian patients. 64 Sicilian patients (33 males and 31 females--51.56% and 48.43% respectively) were observed: and their survival was 81.25% after 48 months. The sample of Campanian octogenarian patients considered for this study included 26 patients (12 males--53.85%--and 14 females--46.15%), observed for a shorter period (36 months). The probabilities of survival after 36 months was 84.61%. To sum up, elderly patients represent a growing reality on dialysis registries in Sicily and Campania. Future research concerning this class of patients should be developed in order to individualize suitable stratification risk indices; knowing patterns and probability of survival might help physicians in the dialysis decision-making process.

Several studies have reported that high sodium (Na) intake increases not only urinary Na but also urinary calcium (Ca), suggesting that high Na intake could be involved in the pathogenesis of hypercalciuria. No research data are available on the relationship of Na intake to the prevalence of hypercalciuria within the general population. Moreover, it is not clear if Na intake relates only to urinary Ca or also to other indices of Ca homeostasis, including intestinal Ca absorption. In the present paper, two distinct studies addressed these points using 24-hour urinary Na as an index of salt intake in individuals on their habitual unrestricted free diet. Study 1 analyzed the relationship between 24-hour urinary Na and hypercalciuria (24-hour urinary Caor = 7.5 mmol in men,or = 6.25 mmol in women) in a population sample of 203 men and women, aged 20-59 years. Study 2 analyzed the relationship between 24-hour urinary Na and intestinal strontium (Sr) absorption, used as an index of intestinal Ca absorption, urinary (24-hour and fasting) and plasma Ca, and plasma parathyroid hormone in 36 healthy men and women, aged 18-65 years. Within the population sample (study 1), 24-hour urinary Na was directly and significantly correlated with prevalence of hypercalciuria when controlling for gender, age, weight, and urinary creatinine: the relationship was continuous and linear for urinary Na ranging between 40 and 200 mmol/24 h. In the 36 volunteers (study 2), 24-hour urinary Na was related to 24-hour and fasting urinary Ca (p0.001) but not to intestinal Sr absorption: the relationship between 24-hour urinary Na and urinary Ca (both 24 h and fasting) was also significant, controlling for other variables. The results indicate that in adults on their habitual diet, urinary Na, which reflects dietary salt intake, correlates with the prevalence of hypercalciuria independently of intestinal Ca absorption and mainly via renal mechanisms.

The study was devised to explore the effects of an acute oral protein load on renal hemodynamic response in patients with IgA nephropathy (IgAN). The study was performed in 10 proteinuric IgAN patients (800 ± 300 mg/day) and in 20 healthy controls (matched by sex, age, BMI, BSA, plasma creatinine, plasma urea, urinary urea and protein intake). Blood pressure and creatinine clearance were nearly identical in the two groups. GFR. and RPF, measured as the clearance of inulin and of p-aminohippurate (PAH) were studied before and after a meat meal which provided 2 g of protein/kg BW. Following the protein load, renal reserve, percent renal reserve and postmeal cumulative changes of GFR were not significantly different in IgAN and controls. Filtration fraction (FF) at baseline was significantly higher (p < 0.01) in IgAN than in controls (25.5 ± 1.41 vs. 19 ± 2%). Postmeal hyperemia and hyperfiltration did not affect FF in either group. Filtration capacity in IgAN was lower (p < 0.02) than in controls (117 ± 5.6 vs. 137.9 ± 7.0ml/min × 1.73 m2), whereas the percent of filtration capacity utilized at rest was identical in controls and in IgAN. Creatinine clearance overestimated GFR in IgAN. The data indicate that renal hemodynamic response to proteins in IgAN is normal. © 1997 S. Karger AG, Basel.

The medical history of salt begins in ancient times and is closely related to different aspects of human history. Salt may be extracted from sea water, mineral deposits, surface encrustations, saline lakes and brine springs. In many inland areas, wood was used as a fuel source for evaporation of brine and this practice led to major deafforestation in central Europe. Salt played a central role in the economies of many regions, and is often reflected in place names. Salt was also used as a basis for population censuses and taxation, and salt monopolies were practised in many states. Salt was sometimes implicated in the outbreak of conflict, e.g. the French Revolution and the Indian War of Independence. Salt has also been invested with many cultural and religious meanings, from the ancient Egyptians to the Middle Ages. Man's innate appetite for salt may be related to his evolution from predominantly vegetarian anthropoids, and it is noteworthy that those people who live mainly on protein and milk or who drink salty water do not generally salt their food, whereas those who live mainly on vegetables, rice and cereals use much more salt. Medicinal use tended to emphasize the positive aspects of salt, e.g. prevention of putrefaction, reduction of tissue swelling, treatment of diarrhea. Evidence was also available to ancient peoples of its relationship to fertility, particularly in domestic animals. The history of salt thus represents a unique example for studying the impact of a widely used dietary substance on different important aspects of man's life, including medical philosophy.

A 62-year-old man was hospitalized for recent renal colic and neurologic disorders. Routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 15.3 mg/100 mL) and renal failure (serum creatinine = 3.72 mg/100 mL). The patient reported that he had been on treatment with a slow-release multivitamin preparation containing vitamin D and vitamin A, administered by i.m. injection. Plasma 25-OH vitamin D was150 ng/mL (normal range 16-74 ng/mL), plasma 1,25-(OH)2 vitamin D was 32.5 pg/mL (normal range 14-60 pg/mL), plasma parathyroid hormone 1.3 pg/mL (normal range 10-65 pg/mL). There were calcifications of left and right iliac artery at abdomen x-ray. Ultrasound and computed tomography of the glutei showed alterations of skeletal muscle and calcifications. Immediate treatment with infusion of isotonic saline, furosemide and prednisone induced rapid control of hypercalcemia and renal failure. Chronic treatment per os was discontinued after six months. The patient reported that the treatment with vitamin D had been prescribed by a physician also to his wife (55-year-old). For the woman, routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 11.3 mg/100 mL) and renal failure (serum creatinine = 1.8 mg/ mL). Plasma 25-OH vitamin D was150 ng/mL, plasma 1,25-(OH)2 vitamin D 47.9 pg/mL, plasma parathyroid hormone was 2.5 pg/mL. Hypercalcemia was acutely treated by oral hydration, furosemide, and prednisone. Chronic treatment per os was discontinued after five months.

Starting November 1973, peritoneal dialyses have been performed 7 days a week on a group of 18 patients, 11 of whom still on the program. A short daily dialysis technique at a dialysate flow of 2.5 L/hour was used. This group of patients has undergone 9,724 dialyses, 86.8% of which at home.A group of 4 patients had to be switched to hemodialysis. During the last 16 months a total of 5,670 short daily dialyses have been performed, 97.4% of which at home.Another group of 6 patients has undergone Continuous Ambulatory Peritoneal Dialysis (CAPD) for 24 hours daily with 10-liter dialysate containing 3-4.25 g/100 ml dextrose. A total of 967 dialyses have been performed. Peritonitis occurred in 7 instances, and 2 patients had to be switched to hemodialysis.In summary, daily dialysis with either schedule reveals itself suitable for home program and requires a much smaller financial effort from the community. The data presented indicate that CAPD constitutes the most physiological approach to the problem of waste ...

Low protein diets, made either of natural foods or of L-essential amino acids and/or their nitrogen-free ketoanalogues, are feasible, safe, and efficient means to reduce disease progression in patients with chronic kidney disease and do not prejudice patient outcomes once they get into Renal Replacement Therapy. They ameliorate symptomatology, grant a positive nitrogen balance, reduce proteinuria, improve osteodystrophy and lipid profile, reduce serum concentrations of uric acid, phosphate, and maintain plasma bicarbonate within normal limits thus preventing metabolic acidosis. They also reduce the number of hypotensive drugs and the quantity of erythropoietin to be administered to achieve target hemoglobin concentrations, and do not deteriorate quality of life. On the contrary, they retard progression of chronic kidney disease. There is a need to motivate patients to increase adherence to prescription and dietitians to escape the risks of malnutrition.

The intravascular volume consists of 40% to 45% red cells. Their production is controlled predominantly by erythropoietin (EPO), a hormone that is secreted particularly when tissue hypoxia is present. Because of this high percentage of the total intravascular volume the question comes to mind that, in addition to hypoxia, can volume-regulation mechanisms, known to be responsible for the maintenance of plasma volume, modulate EPO secretion when the total vascular volume changes? Indeed, there is evidence that in situations in which the intravascular volume or specifically the intrathoracic volume is altered, EPO secretion is affected. EPO secretion increases when the intrathoracic volume decreases 24 hours after water immersion or after endurance exercise when a negative water balance prevails. A head-down tilt on the other side induces central engorgement leading to a decrease of EPO concentrations. Under these experimental conditions no hypoxia was seen, supporting the idea that a Volume stimulus outgoing from intrathoracic parts of the circulation modulated EPO secretion. Further observations from the clinical side are needed to support these ideas and the consequences need to be implemented into clinical practice.

There are scanty data available on alexithymia in patients with end-stage renal disease, which point to an independent association with depression and social support. This study was devised to investigate the prevalence of alexithymia and sleep disorders in patients maintenance hemodialysis with insuppressible secondary hyperparathyroidism, who need parathyroidectomy (PTX), because previous data from our laboratories as well as those of others showed that this patient-group are the worst sleepers among hemodialysis patients with end-stage renal disease. A total of 40 patients needing PTX were enrolled and studied before the surgery. As for the control group, 80 patients on maintenance hemodialysis not needing PTX were enrolled. We measured alexithymia with the Toronto Alexithymia Score (TAS-20), sleep disorders with the Pittsburgh Sleep Quality Index (PSQI), and depression with Beck Depression Inventory (BDI), intact parathyroid hormone (iPTH), calcium, phosphate, use of antihypertensives, systolic and diastolic blood pressure, hemoglobin concentration, and albumin concentration. Patients needing PTX in comparison with those not needing PTX had significantly higher iPTH, calcium, and phosphate; they also had significantly higher systolic and diastolic blood pressure. They were more significantly alexithymic (P < .001), had more severe sleep disorders (P < .001), and were more depressed (P < .043). In multivariate analysis, BDI correlated significantly with iPTH concentration (r = 0.505, P < .001). A reduction of TAS-20 occurred after PTX which correlated with the number of patients on antihypertensive drugs, PSQI, BDI, hemoglobin concentration in the univariate and multivariate analysis. When TAS-20 and PSQI were adjusted for BDI (using analysis of variance) there was still a significant difference of TAS-20 and PSQI between patients needing PTX and not needing PTX (P < .001). This study confirms the high prevalence of sleep disorders in patients with unsuppressed secondary hyperparathyroidism and discloses a high prevalence of Alexithymia which is ameliorated by PTX. However, the correlation of Alexithymia with sleep disorders does not depend on depression.

Sleeping disorders are very common in patients with chronic kidney disease on dialysis (CKD5D) and are an emerging risk factor able to predict mortality. Parathyroid hormone (PTH) although considered a pivotal uremic toxin has rarely been associated with sleep disorders in uremia. In a study from our laboratory PTH concentrations failed to distinguish patients with sleep disorders from those without. In a study performed by Chou et al a 97% prevalence of insomnia was found in patients undergoing hemodialysis requiring parathyroidectomy. Surgery reduced PTH and increased sleeping hours within 3 months. The aim of this study was to study the effects of parathyroidectomy on the sleep disorders of insomniacs on maintenance hemodialysis. The study was performed in 16 insomniac patients on maintenance hemodialysis who successfully underwent surgery with autotransplantation of autologous parathyroid tissue (40 mg) under the skin of the forearm. Patients (5 F and 11 M) were studied from 1 month before surgery to 1 year after. Sleep disorders were assessed by means of a 27-item questionnaire--Sleep Disorder questionnaire (SDQ)--that identified sleeping disorders according to Diagnostic and Statistical Manual of Mental Disorders - IV Edition (DSM-IV) criteria. The Charlson Comorbidity Index (CCI) was also measured along with systolic and diastolic blood pressure, Hb, PTH, Ca, P. A 95.5% prevalence of sleep disorders was found pre operatively. Patients slept 4.90+/-1.2 hours, Ca averaged 10.09+/-0.54 mg/dL, Phosphate 5.5+/-1.93, CCI 9.8+/-1.1, PTH 1498+/-498 ng/mL. After 1 year follow-up 2 out 16 patients had normal sleep, 6 out 16 patients had subclinical sleep disorders and 8 remained insomniacs (p=0.008, Mc Nemar Test for paired data, insomniacs vs. no disturbance + subclinical disorders). Sleeping hours increased up to 6.0+/-1.24 (p

Hydrogen sulfide (H(2)S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H(2)S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H(2)S production. We have recently studied H(2)S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients. Hydrogen sulfide (H2S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H2S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H2S production. We have recently studied H2S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients. Copyright © 2011 S. Karger AG, Basel.

On July 1, 1751, the royal Parisian printer Le Breton published the first volume of the Encyclopédie of Diderot and d'Alembert, a rational dictionary, in folio and in alphabetical order, sold by subscription. The whole work was completed in 1780 (a total of 35 volumes, of which 12 were of illustrations, 4 of supplements and 2 of indices). In 1782 it was followed by the Encyclopédie méthodique, printed by Panckoucke, which ended in 1832 with volume number 166. The frontispiece of the first volume, designed by Charles-Nicolas Cochin Jr. and engraved by Benoît-Louis Prévost showed the columns of an Ionic temple where the Truth appears between Reason and Philosophy. Reason is shown trying to break the veil of Truth, and Philosophy trying to embellish it. Below are the philosophers, their eyes fixed on Truth. Theology is on his knees with his back facing Truth, and seems to receive light from the top. The subsequent chain of figures depicts Memory, Ancient History, Modern History, Geometry, Astronomy and Physics. Below are Optics, Botany, Chemistry and Agriculture. On the bottom line one finds the representatives of arts and professions derived from science. In a 42-page preface ("Discours préliminaire") d'Alembert discussed the path to new knowledge as one "based on what we receive through senses. Ideas depend on senses." The medical collaborators were, or became, famous. Medicine was considered to be rooted in experiment, in patients and in measurements. Functions started to be described with numbers. It was the birth of determinism which was later reinforced by Magendie and Claude Bernard. Albrecht Haller, president of the Academy of Science at Göttingen, as well as a member of all European academies, wrote seminal entries. New accurate definitions appeared for life, disease, death, infections, plague, epidemics, hygiene, fevers and edema. Semiology, the study of signs, became the visible explanation of deranged function, diagnosis and prognosis.

Hydrogen sulfide, H2S, is the third endogenous gas with cardiovascular properties, after nitric oxide and carbon monoxide. H2S is a potent vasorelaxant, and its deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine gamma- lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H2S formation. Chronic kidney disease is characterized by high prevalence of hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially in hemodialysis patients. H2S levels are decreased in hemodialysis patients through transcriptional deregulation of genes encoding for the H2S-producing enzymes. Potential implications relate to the pathogenesis of the manifestations of the uremic syndrome, such as hypertension and atherosclerosis. (C) 2010 by the National Kidney Foundation, Inc. All rights reserved.

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function. © 2009 Wiley Periodicals, Inc.

Item does not contain fulltext BACKGROUND AND OBJECTIVES: Evaluation of renal function by estimation of the glomerular filtration rate (GFR) is very important for the diagnosis and treatment of patients with chronic kidney disease (CKD). The Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas are the most commonly used estimations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Estimated GFR values by each formula were compared with measured GFR (mGFR) by renal inulin clearance in 2208 European adults (46% women, 1.4% Caribbean blacks), with and without CKD, and mean mGFR 72.4 +/- 39.0 (range 2.2 to 177.2) ml/min/1.73 m(2). RESULTS: Overall, the CG and MDRD formulas showed bias (mean difference) -3.5 ml/min/1.73 m(2) (5.3%), P < 0.001, and -9.8 ml/min/1.73 m(2) (-6.4%), P < 0.001; precision (SD of bias) 21.5 ml/min/1.73 m(2) (43.1%) and 20.0 ml/min/1.73 m(2) (33.0%); limits of agreement (2 SD by Bland-Altman method) 39.5 to -46.5 (range 86.0) ml/min/1.73 m(2) and 30.2 to -49.8 (range 80.0) ml/min/1.73 m(2); and accuracy within +/-30% of mGFR 70.8 and 69.0%, respectively. Both formulas showed a trend for decreasing accuracy with lower mGFR levels. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD classification's five GFR groups, the CG and MDRD formulas properly assigned 61.6 and 57.1% of the entire population and had a range of positive predictive values 42.6 to 81.8% and 39.6 to 85.2% and of negative predictive values 81.7 to 96.6% and 76.4 to 97.5%, respectively. CONCLUSIONS: The CG and MDRD formulas had some limitations for proper GFR estimation and K/DOQI-CKD classification by GFR levels alone.

Immobilization-induced bone loss is usually greater in the epiphyses than in the diaphyses. The larger fraction of trabecular bone in the epiphyses than in the diaphyses offers an intuitive explanation to account for this phenomenon. However, recent evidence contradicts this notion and suggests that immobilization-induced bone loss from the distal tibia epiphysis is mainly from the cortical compartment. The aim of this study was to establish whether this pattern of bone loss was a general rule during immobilization. We monitored various skeletal sites with different tissue composition during 5 weeks of immobilization. Ten healthy male volunteers with mean age of 24.3 years (SD 2.6 years) underwent strict horizontal bed rest. Bone scans were obtained during baseline data collection, at the end of bed rest and after 14 days of recovery by peripheral Quantitative Computed Tomography (pQCT). Sectional images were obtained from the distal tibia epiphysis (at 4% of the tibia's length), from the diaphysis (at 38%), from the proximal metaphysis (at 93%) and from the proximal epiphysis (at 98%), as well as from the distal femur epiphysis (at 4% of the femur's length) and from the patella. Relative bone losses were largest at the patella, where they amounted to − 3.2% (SD 1.8%, p < 0.001) of the baseline values, and smallest at the tibia diaphysis, where they amounted to − 0.7% (SD 1.0%, p = 0.019). The relative losses were generally larger from cortical than from trabecular compartments (p = 0.004), and whilst all skeletal sites depicted such cortical losses, substantial trabecular losses were found only from the proximal tibia epiphysis. Results confirm that the differential losses from the various skeletal sites cannot be explained on the basis of trabecular vs. cortical tissue composition differences, but that endocortical circumference can account for the different amounts of bone loss in the tibia. The present study therefore supports the suggestion of the subendocortical layer as a transitional zone, which can readily be transformed into trabecular bone in response to immobilization. The latter will lead to cortical thinning, a factor that has been associated with the risk of fracture and with osteoarthritis.

This article reviews bone adaptation to microgravity, during manned space missions, in humans undergoing Head Down Tilt (HDT) and in Hind-Limb-Suspended Rats. Under microgravity conditions, bone loss occurs in association with hypercalciuria, which in turn modulates Aquaporin 2 (AQP2) excretion in urine, thus avoiding stone forming in space. This report discloses the need to prevent bone loss in order to prepare for long stays at lunar bases or voyages to Mars. (C) 2005 by the National Kidney Foundation, Inc.

Background: Female gender is associated with high erythropoietin (EPO) resistance in end-stage renal disease. The aim of our study was to investigate the roles of age and menstrual status in this relationship. Methods: Cross-sectional analysis of registry data for 3,224 hemodialysis adults treated with EPO. Data collection included gender, age, weight, height, dialytic age, hemoglobin, EPO dose, and, for women with ages 25–44 only, also information on menstrual status and iron homeostasis. EPO resistance index (ERI) was calculated as EPO dose per kilogram BW/hemoglobin. Results: Men and women had not significantly different hemoglobin and significantly different EPO dose per kilogram weight (women vs. men, +18.2%, p < 0.001). Thus, ERI was higher in women than in men (+19.5%, p < 0.001). The gender-associated difference in ERI linearly decreased along age groups: +30.9% for ages 25–44, +23.2% for ages 45–64, and +14.2% for ages 65–84 (p < 0.05 for interaction between age and gender-associated difference in ERI). Within the subgroup of women with ages 25–44, women with menses in comparison to women without had 44.6% higher ERI (p < 0.01) due to combination of lower hemoglobin (p < 0.05) with higher EPO dose (p < 0.001). Women with menses had also lower serum iron, transferrin saturation, and serum ferritin (p < 0.001). Conclusion: The gender-associated difference in ERI is lower with increasing patients’ age. The large difference between young men and women is due to women with menses who have iron deficiency more frequently than women without periods.

Plasma proteins containing damaged L-isoaspartyl residues are increased in uremia: Implications for mechanism.BackgroundSeveral alterations of protein structure and function have been reported in uremia. Impairment of a transmethylation-dependent protein repair mechanism possibly related to a derangement in homocysteine metabolism is also present in this condition, causing erythrocyte membrane protein damage. Homocysteine may affect proteins via the accumulation of its parent compound S-adenosylhomocysteine (AdoHcy), a powerful in vivo methyltransferase inhibitor. However, since plasma homocysteine is mostly protein bound, a direct influence on protein structures cannot be ruled out. We measured the levels of L-isoaspartyl residues in plasma proteins of uremic patients on hemodialysis. These damaged residues are markers of molecular age, which accumulate when transmethylation-dependent protein repair is inhibited and/or protein instability is increased.MethodsL-isoaspartyl residues in plasma proteins were quantitated using human recombinant protein carboxyl methyl transferase (PCMT). Plasma concentrations of homocysteine metabolites were also measured under different experimental conditions in hemodialysis patients.ResultsThe concentration of damaged plasma proteins was increased almost twofold compared to control (controls 147.83 ± 17.75, uremics 282.80 ± 26.40 pmol of incorporated methyl groups/mg protein, P < 0.003). The major protein involved comigrated with serum albumin. Although hyperhomocysteinemia caused a redistribution of thiols bound to plasma proteins, this mechanism did not significantly contribute to the increase in isoaspartyl residues. The S-adenosylmethionine (AdoMet)/AdoHcy concentration ratio, an indicator of the flux of methyl group transfer, was altered. This ratio was partially corrected by folate treatment (0.385 ± 0.046 vs. 0.682 ± 0.115, P < 0.01), but protein L-isoaspartate content was not.ConclusionsPlasma protein damage, as determined by protein L-isoaspartyl content, is increased in uremia. This alteration is to be ascribed to an increased protein structural instability, rather than the effect of hyperhomocysteinemia.

Background: Exposure to microgravity or immobilization results in alterations of renal function, fluid redistribution and bone loss, which couples to a rise of urinary calcium excretion. We recently demonstrated that high calcium delivery to the collecting duct reduces local Aquaporin-2 (AQP2) mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration and reducing calcium saturation. To investigate renal water balance adaptation during bed rest, a model to mimic the effects of microgravity on earth, the effect of changes in urinary calcium on urinary AQP2 excretion were assessed. Methods: Ten healthy men (aged 21-28 years) participated in the experiment. Study design included 7 days of adaptation and 35 days of continuous bed rest (days -6 to 0 and 1 to 35, respectively) under controlled diet. Food records and 24-hour urine samples were collected daily from day -3 to 35. Changes in blood hematocrit were used as an indirect index of plasma volume changes. AQP2 excretion was measured by ELISA. Results: Bed rest induced bone demineralization and a transient increase in urinary calcium followed by transient decrease in AQP2 excretion, which can reduce the urine concentrating ability causing plasma volume reduction. The return of calciuria to baseline was followed by a recovery of AQP2 excretion, which allows for a partial restoration of plasma volume. Conclusions: These results further support the view that urinary calcium can modulate the vasopressin-dependent urine concentration through a down-regulation of AQP2 expression/trafficking. This mechanism could have a key role in the prevention of urine super-saturation due to hypercalciuria.

Bone demineralization due to immobilization was associated with transient increases in plasma/urinary Ca and a sustained PTH suppression which, in turn, induced secondary changes in plasma P and 1,25-(OH)2 vitamin D.

Survival is not enough is a yearly international event started in 2007 in Naples, Italy, in the week of the World Kidney Day to discuss the needs of renal patients and the quality of life of a category of patients living a machine-dependent life. Renal patients and their associations, philosophers, economists, nephrologists, and health care managers are enrolled to discuss about the possibility to grant the best cures and care without reducing the quality and the quantity of the services the patients need. Various quests have arisen for (1) a new cadre of managers capable of keeping health accounts in balance without cutting expenditure but by reducing waste of resources, (2) the promotion of prevention as the only measure capable of reducing costs in the long run, and (3) the promotion of clinical and translational research. The changes occurring in the health system should be viewed as a window of opportunity, including the advent of the medical-industrial complex firstly described in 1980, an event originating in the United States of America and now spreading worldwide. © 2012 National Kidney Foundation, Inc.

Objective: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. Design: The study is an open, parallel, intervention study. Setting: Ambulatory chronic hemodialysis patients. Subjects: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). Intervention: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). Main Outcome Measure: Plasma homocysteine measured before and after dialysis at the first and the last treatment. Results: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level

Few studies have addressed the problem of sleep disturbances in patients with early-stage chronic kidney disease (CKD). A total of 220 patients newly diagnosed with CKD and 220 patients newly diagnosed with chronic hepatitis C were studied within 1 month from the diagnosis. They were evaluated by using the Charlson Comorbidity Index, the Pittsburgh Sleep Quality Index, and the Beck Depression Inventory. Patients with CKD were followed up for 4 years. Sleep disturbances affected 59.5% of patients with chronic hepatitis C and 84.6% of patients with CKD. Sleeping disorders that were severe and peculiar in early CKD improved significantly over time. Beck Depression Inventory disclosed significant depression, which was ameliorated over time. Charlson Comorbidity Index was constant over time. Logistic regression analysis failed to detect significant correlations for putative factors emerging from studies in hemodialyzed patients, with the exception of depression.

The evaluation of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) is suggested for the assessment of cardiovascular risk. It is unclear whether UAE and eGFR provide complementary information. UAE, eGFR, cardiovascular risk factors, and the incidence of cardiovascular disease were analyzed in 45- to 64-year-old individuals involved in the Gubbio study. UAE in the highest decile was defined as high (microng/min: > or = 18.6 in men and > or = 15.7 in women), eGFR in the lowest decile as low (mL/min/1.73 m(2)

Background. Available data indicate that serum phosphate increases only when glomerular filtration rate (GFR) falls into the low range (

The paper deals with the use of estimated glomerular filtration rate (eGFR) as marker of low kidney function in the population. Data were collected on serum creatinine, other laboratory indices, blood pressure, and medical history in a population sample of 2083 men and 2491 women aged between 18-95 years. Estimated GFR was calculated by the equation of Modification Diet in Renal Disease study. Disorders included in the analysis were hypertension, cardiovascular disease, high serum uric acid, high serum phosphorus/low serum calcium, anemia, and high serum potassium. Prevalence of low eGFR (eGFR60 mL/min per 1.73 m2) increased with age: from1% for ages 18-24 to30% for agesor =75, P0.001. On the basis of these data, prevalence of low eGFR in the adult Italian population was 5.7% for men (n=1.3 million, 95%CI = 1.1/1.5) and 6.2% for women (n=1.5 million, 95%CI = 1.3/1.8). Disorders associated with kidney dysfunction were two or more in the majority of persons with low eGFR and were more frequent with lower eGFR (p0.001). Previous diagnosis of kidney disease was reported by less than 5% in people with low eGFR and was progressively higher with higher serum creatinine or with number of associated disorders (p0.03). Hypertension tended to be more frequently treated but not more frequently controlled in people with low eGFR. Data support the use of eGFR to identify people with or at risk of low kidney function. Awareness of kidney disease is low in people with low eGFR unless serum creatinine is very high or they have many associated disorders.

Estimated glomerular filtration rate (eGFR) and urinary albumin (U-Alb) have been suggested as indicators for the early identification of persons with kidney dysfunction. The Gubbio Study collected data on serum creatinine, UAlb, other laboratory indices, blood pressure, and medical history in a population sample of 4574 adults (2083 men and 2491 women, age range 18- 95 years). The study included analyses on six disorders which are commonly associated with kidney disease (hypertension, cardiovascular disease, anemia, high serum uric acid, high serum phosphorus/low serum calcium, and high serum potassium). Low eGFR ( 30% at > or =75 years in both sexes, p or =20 microg/min) in the presence of non-low eGFR. Low eGFR was associated with at least two disorders potentially due to kidney disease in the majority of persons but was rarely associated with a previous diagnosis of kidney disease (

We need a new health care system that is based on patients' needs. The present cadre of health managers who acquired power by cutting expenditures must be removed from office. We need to educate a new cadre of health managers who are 1) convinced that safeguarding health does not use up the resources of the next generations; 2) capable of switching the system from curative to preventive medicine; and 3) able to reinforce clinical research. Such principles have been recently adopted by the French President Sarkozy in devising the national health care program.

Survival is not enough. We need to build a health system starting from patients' needs without wasting the resources of our grandchildren and great-grandchildren. We have to switch from curative to preventive medicine by firing managers who think they can resolve all problems by cutting expenditures. We need to educate a new cadre of managers able to govern by centering the system on the patients. Managers should consider health care as an asset and should reinforce clinical research. Such a program has been recently adopted in France.

High levels of homocysteine have been implicated as a cardiovascular risk factor in the general population and in patients with chronic renal failure, and particularly patients on hemodialysis. To classify a risk factor as causally related to a certain disease, both strong epidemiologic data and sound basic-science studies establishing a mechanism are needed. Among the latter, the hypomethylation of proteins and DNA, and protein homocysteinylation, have been investigated in uremia, providing for an array of toxic effects in this disease. © 2008 National Kidney Foundation, Inc.

Background This study investigated prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients. Methods A cross-sectional analysis was performed on registry data for 2,746 chronic (Results Prevalence was 88.7% for anemia (hemoglobin 2) were independent correlates of anemia (PConclusion Anemia and uncontrolled anemia are more frequent in hemodialysis patients with short-term dialysis, diseases other than HCKD, low BMI, and female gender. Gender effect was lower in elderly patients. Uncontrolled anemia was also associated with low serum albumin and calcium, suggesting that these parameters are indices of EPO resistance.

Background: L-Carnitine, the acyl carrier into mitochondria, is derived from trimethyllysine. The formation of the latter compound is catalyzed by an S-adenosylmethionine methyltransferase, yielding S-adenosylhomocysteine (AdoHcy), the homocysteine direct precursor, as a product. Aim of this work was to determine if exogenously administered L-propionyl carnitine affects plasma levels of homocysteine, a cardiovascular risk factor, and its active metabolite AdoHcy, in chronic renal failure patients on hemodialysis. Methods: Plasma homocysteine and AdoHcy were determined by means of HPLC separation and detection in 14 hemodialysis patients before and after two months of i.v. L-propionyl carnitine treatment. Results: No significant differences were observed in plasma concentrations of homocysteine or AdoHcy after therapy. Conclusions: Treatment with a carnitine derivative does not significantly influence the plasma concentrations of homocysteine or of its active metabolite, AdoHcy, which are involved as risk factors for cardiovascular disease in chronic hemodialysis patients. © Società Italiana di Nefrologia.

About 85% of patients on maintenance hemodialysis have sleep disorders that depend on comorbidities, age, morning dialytic shift, and blood pressure. They are ameliorated by erythropoietin, by transplantation, and by daily and nocturnal dialysis. Some data exist on sleep disorders in CKD patients, and show that lack of a refreshing sleep is present even at early stages of the disease and may affect 82.2% of patients without any relationship to comorbidities.

Background: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate.Methods: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated.Results: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1mEq/L, whereas it averaged 21.1 +/- 0.7mEq/L in patients on calcium carbonate (p < 0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p < 0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

Cardiopulmonary bypass induces a systemic inflammatory response (SIR), characterized by the activation of cellular and humoral elements, with concomitant release of neutrophil elastase and matrix-metallo proteinases. In the present study, the protease release during extracorporeal circulation in 28 patients undergoing cardiac surgical operations was monitored using casein zymography. A peak in protease activity was found in all patients at the end of cardiopulmonary bypass. Plasma samples of patients were allowed to interact with different traps obtained by immobilizing different protease inhibitors on specific carriers. α1-Antitpypsin, Bovine Pancreatic Trypsin Inhibitor, Elastatinal or Leupeptin were used as inhibitors and were covalently immobilized by diazotization or by condensation. A reduction in the proteolytic activity of the plasma samples was observed after interaction with the different traps. The most efficient traps, i.e. the ones displaying greatest power to inhibit protease activity, were those obtained by immobilizing Bovine Pancreatic Trypsin Inhibitor and Leupeptin. The biocompatibility of traps was also tested. Results show that protease activity in blood can be decreased by our protease traps.