Search

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.

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.

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 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.

The organometal cisplatin has potent antitumor properties. However, its use is sometimes complicated by significant nephrotoxicity. This is characterized by tubular necrosis and impairment of the glomerular filtration rate (GFR). On the other hand, it has been demonstrated that atrial natriuretic factor (ANF) increases GFR in normal euvolemic rats. In the present study, we have therefore tested if this new potent natriuretic compound could restore some of the renal parameters affected by cisplatin. To investigate this issue, acute renal failure was induced in 9 rats by intraperitoneal injection of cisplatin 10 mg/kg body weight (b.w.). Renal function was studied 72 h later using the 3H-inulin clearance method and was compared with the renal function of 5 normal euvolemic rats. The cisplatin-treated rats showed high blood urea nitrogen levels, a 74% reduction of whole kidney GFR (0.308 +/- 0.047 vs. 1.17 +/- 0.08 ml/min/100 g b.w.) and a significant increase in the fractional excretion of urine, sodium and potassium. After 2 control clearances, synthetic ANF was administered intravenously as a prime (12 micrograms/kg b.w.) and then as a constant infusion (1 microgram/kg/min) to 6 cisplatin-treated rats. This promptly doubled the GFR (0.603 +/- 0.113 ml/min/100 g b.w.) and induced a significant increase in the excretion rate of urine, sodium and potassium. These results demonstrate that the administration of ANF has a beneficial effect on the experimental model of acute renal failure induced by cisplatin.

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.

BackgroundThe antidiuretic hormone (ADH) or arginine vasopressin (AVP) regulates the body's water balance. Recently, modifications in AVP levels have been related to osteoporosis during ageing and microgravity/bed rest. Therefore the present study was devised to assess whether the absence of AVP, as in patients with central diabetes insipidus (CDI), modulates renal calcium excretion.MethodsWe retrospectively analysed data from 12 patients with CDI with measured 24-h urinary excretion levels of calcium. Data were available at the moment of the diagnosis when patients were drug-free and after therapy with dDAVP, an analog of AVP. Hypercalciuria was defined as 24-h urinary Ca2+ >275 mg/day in males and >250 mg/day in females and a urinary calcium (Ca):creatinine (Cr) ratio >0.20 mg/mg.ResultsUntreated CDI patients had a daily urinary Ca2+ excretion of 383 ± 47 mg/day and a urinary Ca:Cr ratio of 0.26 ± 0.38 mg/mg. The urine osmolarity significantly increased after the administration of dDAVP by 210% and the urinary flow decreased by 72%. Furthermore, the estimated glomerular filtration rate (eGFR) increased by 7%, which did not reach statistical significance. dDAVP treatment did not significantly modify the urinary Ca2+ concentration; however, the daily calcium excretion and the urinary Ca:Cr ratio were significantly decreased (160 ± 27 mg/day and 0.11 ± 0.02 mg/mg, respectively).ConclusionsPatients with CDI show hypercalciuria even though urine is more diluted than normal controls, and dDAVP reverses this effect. These data support the intriguing relationship between AVP and osteoporosis in ageing and microgravity/bed rest.

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.

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.

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

Robert James was a member of the College of Physicians at Cambridge and a practitioner. He was considered one of the "three best known characters in London - perhaps in Europe. The other two being the lexycographer Samuel Johnson and the Shakespearean actor David Garrick." James became famous for his powerful ability to write and publish, which produced many books, including the ponderous A Medicinal Dictionary, With a History of Drugs, in 3 volumes in folio, published in London in the years 1743-1745, and dedicated to the famous professor and royal physician John Mead.The Dictionary was translated into French by Denis Diderot, Francois-Vincent Toussaint and Marc Antoine Eidous, and was revised by Juliene T. Busson, president of the University of Paris. During the translation, Diderot learned much biology and medicine, which he used subsequently in developing his Encyclopedie. Interesting chapters are devoted to urine, predictions from urine, bloody urine, good urine, bad urine, urine portending death, diabetes, dropsy, nephritis, stone, ischury, dysury and urine incontinence. In general their strength resides in their accurate clinical descriptions. The paragraphs on urine are concise and clinically sound, and the description of procedures for urine analysis and the utilization of results (quantity, quantity, colors, sediments and consistency) in diagnosis and prognosis of bloody urine is accurate. The section on diabetes is excellent and is comparable to that of Desault written decades later in the Encyclopedie of Diderot. In the chapter on dropsy (he does not use the word oedema), patients are well described and their remedies are appropriate for the time. The contributions of kidney and liver are clear. The plants for renal treatment can be traced to Dioscorides. Concerning dosage, he is precise and helpful to his readers. The chapter on stones is a real masterpiece, clinically well centered and giving all the pertinent information to localize them, their medical treatment and the risks of surgery. The entry on nephritis is short and rather confusing. Here James even lacks the usual accurate description of cases which could have made it understandable. Blood letting was extensively used in those days, and he is a man of his time, but James was aware of the clinical conditions where it fails. It is understandable that he underlines its role in certain bloody urines in patients with a plethoric constitution. Was James referring to patients with acute nephritis and possibly high blood pressure.

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.

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

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.

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.

Cardiovascular disease is a major cause of morbidity and mortality in chronic kidney disease. Radionuclide-based methods can be used for analyses on the perfusion of coronary arteries and ventricular function. The present study reports the use of a new procedure for continuous measurements of left ventricle function during a dialytic session with the use of a recently developed portable gamma radiation detector (ventricular function study system). On average, left ventricle ejection fraction and stroke volume progressively and continuously decreased throughout the session (end session versus baseline: -13.8% for ejection fraction, -25.9% for stroke volume, P < .02). A biphasic response was found for heart rate: a transient modest decrease (at session midpoint, -4.2%) followed by an increase up to values higher than baseline (end session, +4.7%). Cardiac output decreased by 10.4% at session midpoint (P = .023 versus baseline) without further reduction in the following hours. Mean changes in systolic pressure paralleled data for cardiac output. Individual changes in indices of left ventricle function were scattered and strongly were correlated with thickness of interventricular septum and telediastolic left ventricular volume measured by standard echocardiogram in the interdialytic period (R > .75, P < .05). Data indicate that the ventricular function study system could be a powerful tool for characterization of the profile of left ventricular function in hemodialyzed patients. © 2006 Elsevier Inc. All rights reserved.

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6°, water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights. © 2005 Elsevier Inc. All rights reserved.

Renal dysfunction is a constant feature of congestive heart failure and is a stronger predictor of mortality than left ventricular ejection fraction or New York Heart Association classification. In heart failure, a reduction of glomerular filtration rate and renal plasma flow occurs, although the filtration fraction increases. There are many reason for this pattern. A reduction in effective circulating volume stimulates sympathetic activity and the renin-angiotensin-aldosterone system, and it is associated with increased concentrations of atrial natriuretic peptide, brain natriuretic peptide, and tumor necrosis factor α. Because in chronic kidney disease heart dysfunction commonly is present, an efficient cardiologist-nephrologist interaction should be promoted. © 2005 Elsevier Inc. All rights reserved.