Adamasco Cupisti

Plasma Parameters of the Prothrombotic State in Chronic Uremia

We measured plasma parameters of the prothrombotic state, namely thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA). D-dimer (DD), von Willebrand factor (vWF), tissue-type plasminogen activator (tPA), beta-thromboglobulin (beta TG), platelet factor 4 (PF4) and serotonin (5HT) in a series of 51 adult patients with chronic uremia: 22 were on maintenance hemodialysis (MHD) and 29 on conservative dietary treatment. Serum tumor necrosis factor alpha (TNF) was determined as well. Uremics presented significantly higher levels of TAT, FPA, DD, vWF, TNF, beta TG and 5HT than normal controls. Patients on conservative treatment showed lower levels of TAT, DD, TNF and beta TG than patients on MHD. Our results provide evidence that a prothrombotic state exists in chronic uremia and that MHD patients have a higher degree of hypercoagulation. Both hemodialysis procedure and uremia-related factors are likely to contribute to the hemostatic derangement.

Incremental Hemodialysis, Residual Kidney Function, and Mortality Risk in Incident Dialysis Patients: A Cohort Study

BACKGROUND Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patients residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. STUDY DESIGN A longitudinal cohort. SETTING & PARTICIPANTS 23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year. PREDICTOR Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time. OUTCOMES Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year. RESULTS Among 23,645 included patients, 51% had substantial renal urea clearance (≥3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (≤3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d. LIMITATIONS Potential selection bias and wide CIs. CONCLUSIONS Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.

Potassium Removal Increases the QTc Interval Dispersion during Hemodialysis

This study was planned to clarify the mechanism(s) by which hemodialysis increases the QTc dispersion, a marker of risk of ventricular arrhythmias. To this aim, 10 uremic patients, without any relevant heart diseases, underwent two different types of hemodialysis schedules. In the first, 1 h of isolated high rate ultrafiltration preceded the standard diffusive procedure. In the second, during the first hour of standard bicarbonate hemodialysis, the decrease of plasma potassium concentration was prevented by increasing K+ concentration in the dialysate, according to its pre dialysis plasma levels. During the high rate ultrafiltration period, together with ECG signs of increased sympathetic nervous system activity and catecholamines secretion, the QTc dispersion did not change significantly. Instead, an evident increment was observed 1 h after the start of the diffusive hemodialysis, then slowly progressing until the end of the dialysis and finally returning to the pre dialysis values within 2 h after the end of the session. To the contrary, the increase of the QTc dispersion was totally blunted during a standard hemodialysis procedure in absence of plasma K+ decrease, but appeared again when the K+ dialysate fluid concentration was restored to 2 mmol/l. This study provides evidence that the increase of QTc dispersion occurring on hemodialysis is mainly related to the diffusive process, more precisely to the K+ removal. This is one more reason to focus attention on K+ removal rate especially when hemodialysis treatment is given in uremics affected by cardiac diseases with high risk of arrhythmias.

A Low-Nitrogen Low-Phosphorus Vegan Diet for Patients with Chronic Renal Failure

The nutritional treatment of chronic renal failure with a low-protein low-phosphorus diet (conventional low-protein diet, CLPD) is effective in reducing uremic intoxication, slowing the progression of renal failure and preventing secondary hyperparathyroidism. Unfortunately, in some patients, the poor palatability and the high cost of the protein-free substitutes, together with difficulties in following the diet away from home, can make good compliance difficult, possibly causing low energy intake and malnutrition. Here the results are reported of an attempt we made to overcome these drawbacks, using a diet supplying only natural foods of plant origin in definite proportions to give an essential amino acid supply satisfying the recommended dietary allowance. This is possible thanks to an appropriate cereal-legume mixture, supplying proteins complementary for essential amino acids. Additional positive features of this special vegan diet (SVD) are the high ratio of unsaturated to saturated fatty acids, the absence of cholesterol, and the lower net acid production in comparison with a mixed diet. This study indicates that the results obtained with the SVD are similar to those obtained with the CLPD. Therefore the SVD can be a substitute for the CLPD in the management of patients with mild chronic renal failure. The SVD is the diet of choice when products made of starch are not available or poorly tolerated.

Management of natural and added dietary phosphorus burden in kidney disease.

Phosphorus retention occurs from higher dietary phosphorus intake relative to its renal excretion or dialysis removal. In the gastrointestinal tract the naturally existing organic phosphorus is only partially (∼60%) absorbable; however, this absorption varies widely and is lower for plant-based phosphorus including phytate (<40%) and higher for foods enhanced with inorganic phosphorus-containing preservatives (>80%). The latter phosphorus often remains unrecognized by patients and health care professionals, even though it is widely used in contemporary diets, in particular, low-cost foods. In a nonenhanced mixed diet, digestible phosphorus correlates closely with total protein content, making protein-rich foods a main source of natural phosphorus. Phosphorus burden is limited more appropriately in predialysis patients who are on a low-protein diet (∼0.6 g/kg/d), whereas dialysis patients who require higher protein intake (∼1.2 g/kg/d) are subject to a higher dietary phosphorus load. An effective and patient-friendly approach to reduce phosphorus intake without depriving patients of adequate proteins is to educate patients to avoid foods with high phosphorus relative to protein such as egg yolk and those with high amounts of phosphorus-based preservatives such as certain soft drinks and enhanced cheese and meat. Phosphorus rich foods should be prepared by boiling, which reduces phosphorus as well as sodium and potassium content, or by other types of cooking-induced demineralization. The dose of phosphorus-binding therapy should be adjusted separately for the amount and absorbability of phosphorus in each meal. Dietician counseling to address the emerging aspects of dietary phosphorus management is instrumental for achieving a reduction of phosphorus load.

Effect of Hemodialysis on the Dispersion of the QTc Interval

The QTc dispersion reflects the underlying regional heterogeneity of the recovery of the ventricular excitability, thereby it is considered as a novel marker of risk of ventricular arrhythmias. Because a higher incidence of ventricular arrhythmias is described during and after hemodialysis, the aim of this study has been to evaluate the QTc dispersion before and after uncomplicated hemodialysis session. Twenty chronic uremics without heart failure, ischemic heart disease or dialysis hypotension were selected. The QTc dispersion was determined as the difference between the longer and the shorter QTc interval measured on a 12-lead electrocardiogram. Following the hemodialysis session, the QTc dispersion increased from 30 ± 9 to 54 ± 17 ms (p < 0.001) associated with the expected reduction of potassium and magnesium and with the increase of extracellular calcium concentration. However, no correlation has been observed between the QTc dispersion increase and the degree of the intradialytic changes of plasma electrolytes, blood pressure or body weight. In summary, the hemodialysis treatment per se does induce an increase of the QTc dispersion, likely due to the rapid changes of electrolyte plasma concentrations. This can potentially contribute to the arrhythmogenic effect of the hemodialysis procedure, reflecting an enhanced regional heterogeneity of ventricular repolarization. The clinical importance of the increase of QTc dispersion as risk factor of ventricular arrhythmias, particularly in hemodialyzed patients suffering from ischemic or hypertrophic heart diseases, should be the matter of further investigations.

Left ventricular function and calcium phosphate plasma levels in uraemic patients.

Background.  Recent investigations have focused on the pathogenetic role of disturbances of calcium phosphate metabolism in causing cardiovascular morbidity and mortality in haemodialysis patients. The aim of the present study was to assess left ventricular function and its relationship to phosphate and calcium plasma levels in stable uraemic patients on haemodialysis treatment.

The incremental treatment of ESRD: a low-protein diet combined with weekly hemodialysis may be beneficial for selected patients

BackgroundInfrequent dialysis, namely once-a-week session combined with very low-protein, low-phosphorus diet supplemented with ketoacids was reported as a useful treatment schedule for ESRD patients with markedly reduced residual renal function but preserved urine output. This study reports our findings from the application of a weekly dialysis schedule plus less severe protein restriction (standard low-protein low-phosphorus diet) in stage 5 CKD patients with consistent dietary discipline.MethodsThis is a multicenter, prospective controlled study, including 68 incident CKD patients followed in a pre-dialysis clinic with Glomerular Filtration Rate 5 to 10 ml/min/1.73/ m2 who became unstable on the only medical treatment. They were offered to begin a Combined Diet Dialysis Program (CDDP) or a standard thrice-a-week hemodialysis (THD): 38 patients joined the CDDP, whereas 30 patients chose THD. Patients were studied at baseline, 6 and 12 months; hospitalization and survival rate were followed-up for 24 months.ResultsVolume output and residual renal function were maintained in the CDDP Group while those features dropped quickly in THD Group. Throughout the study, CDDP patients had a lower erythropoietin resistance index, lower β2 microglobulin levels and lower need for cinacalcet of phosphate binders than THD, and stable parameters of nutritional status. At 24 month follow-up, 39.4% of patients were still on CDDP; survival rates were 94.7% and 86.8% for CDDP and THD patients, respectively, but hospitalization rate was much higher in THD than in CDDP patients. The cost per patient per year resulted significantly lower in CDDP than in THD Group.ConclusionsThis study shows that a CDDP served to protect the residual renal function, to maintain urine volume output and to preserve a good nutritional status. CDDP also blunted the rapid β2 microglobulin increase and resulted in better control of anemia and calcium-phosphate abnormalities. CDDP was also associated with a lower hospitalization rate and reduced need of erythropoietin, as well as of drugs used for treatment of calcium-phosphate abnormalities, thus leading to a significant cost-saving. We concluded that in selected ESRD patients with preserved urine output attitude to protein restriction, CDDP may be a beneficial choice for an incremental hemodialysis program.

Keto Acid Therapy in Predialysis Chronic Kidney Disease Patients: Final Consensus

*Department of Nephrology, Centre Hospitalier Universitaire et Universitea Bordeaux II, Bordeaux, France.†Nephrology Dialysis and Renal Transplantation Unit, University Hospital ‘‘S. Giovanni di Dio e Ruggi d’Aragona’’, Salerno, Italy.‡Department of Nephrology, Hopital Pellegrin, Bordeaux, France.§Aurad-Aquitaine, Gradignan, France.{Nephrology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy.**Division of Nephrology, Department of Internal Medicine, Istanbul School of Medicine, Istanbul University, Capa, Istanbul, Turkey.††Departement de Nephrologie, H^opital E. Herriot, Lyon Cedex, France.‡‡‘‘Dr. Carol Davila’’ Teaching Hospital of Nephrology, Bucharest, Romania.§§Chinese Society of Nephrology, International Society of Nephrology, and Division of Nephrology, Huashan Hospital, Fudan University,Shanghai, People’s Republic of China.{{Division of Nephrology, Baylor College of Medicine, Houston, Texas.***Department of Nephrology, Institute for Clinical and Experimental Medicine and Institute for Postgradual Education, Prague, CzechRepublic.‡‡‡Dialysis Center No. 9, Health Care Service PLC, Euro Care Hungary, Szekesfehervar, Hungary.§§§The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China.FinancialDisclosure:TheauthorsbelongtotheFreseniusKabiKetoanalogueAdvisoryBoardandparticipatedinthe5thInternationalAdvisoryBoardMeeting,Vevey,Switzerland,May29,2010.ConsultancyfeesandtravelgrantswerereceivedfromFreseniusKabi.Thearticleswerepub-lished as part of a supplement sponsored by an unrestricted educational grant from Fresenius Kabi.AddressreprintrequeststoPhilippeChauveau,ServicedeNephrologie,HopitalPellegrin,CHUdeBordeaux,PlaceAmelieRabaLeon,33000,Bordeaux, France.

Assessment of habitual physical activity and energy expenditure in dialysis patients and relationships to nutritional parameters

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