Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation.

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15-49ml/min) and those on dialysis.

Pathophysiology of the cardio-renal syndromes types 1-5: An uptodate.

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome (CRS) has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS (acute cardio- renal syndrome) is characterized by acute worsening of cardiac function leading to AKI (5, 6) in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury (AKI), while type 4 represent cardiovascular involvement in chronic kidney disese (CKD) patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases.

Subendocardial viability ratio predicts cardiovascular mortality in chronic kidney disease patients.

BACKGROUND: The subendocardial viability ratio (SEVR), calculated by pulse wave analysis, is an index of myocardial oxygen supply and demand. Here we analyze the relation between SEVR and cardiovascular mortality in the chronic kidney disease (CKD) population of a post hoc analysis of a multicenter, prospective, randomized, nonblinded study. METHODS: We studied 212 consecutive asymptomatic outpatients receiving care at 12 nephrology clinics in south Italy. Inclusion criteria were age >18 years, 6 months of follow-up before the enrollment and stage 3-4 CKD. RESULTS: During follow-up, 34 subjects died, 29 of them for cardiovascular causes. SEVR correlated inversely with vascular calcifications (r = -0.37) and myocardial mass (r = -0.45); SEVR changed from 1.33 ± 0.24 to 1.36 ± 0.16 (p = NS; baseline and final values, respectively) in living patients, and from 1.16 ± 0.31 to 0.68 ± 0.26 in deceased patients (p < 0.001). Kaplan-Meier curves show that that a greater reduction of SEVR values during the study (third tertile) significantly predicts cardiovascular mortality (p < 0.0001). CONCLUSIONS: This post hoc analysis shows that a reduction of SEVR values impacts cardiovascular mortality in CKD patients.

Sleep disorders in kidney disease.

Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

[Acute and persistent antiproteinuric effect of a low-protein diet in chronic kidney disease]. / Acuto e persistente effetto antiproteinurico della dieta ipoproteica artificiale nella malattia renale cronica.

This study aimed to evaluate the anti-proteinuric effect of a very-low-protein diet supplemented with essential amino acids and keto analogs in patients with moderate to advanced chronic kidney disease and proteinuria already treated with both ACE inhibitors and angiotensin-receptor blockers. The study was a prospective randomized controlled cross-over trial comparing a very-low-protein diet (VLpD) and a low-protein diet (LpD). We enrolled 32 consecutive patients between June 2000 and June 2005. They were randomized to receive a VpLD (group A) or an LpD (group B) for 6 months; thereafter, patients of both groups were switched to the other diet (group A to LpD; group B to VpLD) for a further 6 months. Finally, all patients were randomized again within each group to receive either LpD or VLpD and were followed for another year. The VLpD group showed a significant reduction of urinary protein excretion during the diet period, with a nadir at the fourth month of treatment; the amount of urinary protein reduction was about 58%. Serum advanced glycation end products (AGE) significantly decreased in 10 patients (5 of group A, 5 of group B; -18% and -19%, respectively) during VLpD. Univariate analysis showed that proteinuria correlated indirectly with VpLD and directly with AGE. This study demonstrates that in patients with moderate to advanced chronic kidney disease and severe proteinuria, a VLpD reduces both proteinuria and serum AGE, even in the presence of complete inhibition of the renin-angiotensin system.

High-tone external muscle stimulation in end-stage renal disease: effects on symptomatic diabetic and uremic peripheral neuropathy.

OBJECTIVE AND DESIGN: Pain and peripheral neuropathy are frequent complications of end-stage renal disease (ESRD). Because drug treatment is associated with numerous side effects and is largely ineffective in many maintenance hemodialysis (MHD) patients, nonpharmacologic strategies such as electrotherapy are a potential recourse. Among various forms of electrostimulation, high-tone external muscle stimulation (HTEMS) is a promising alternative treatment for symptomatic diabetic peripheral polyneuropathy (PPN), as demonstrated in a short-term study. Based on these novel findings, we performed a prospective, nonrandomized, pilot trial in MHD patients to determine (1) whether HTEMS is also effective in treating diabetic PPN in the uremic state, and (2) whether uremic PPN is similarly modulated. PATIENTS AND INTERVENTIONS: In total, 40 MHD patients diagnosed with symptomatic PPN (25 with diabetic and 15 with uremic PPN) were enrolled. Both lower extremities were treated intradialytically with HTEMS for 1 hour, three times a week. Initially, a subgroup of 12 patients was followed for 4 weeks, and a further 28 patients for 12 weeks. The patients' degree of neuropathy was graded at baseline before HTEMS and after 1 and 3 months, respectively. Five neuropathic symptoms (tingling, burning, pain, numbness, and numbness in painful areas) as well as sleep disturbances were measured, using the 10-point Neuropathic Pain Scale of Galer and Jensen (Neurology 48:332-338, 1997). A positive response was defined as the improvement of one symptom or more, by at least 3 points. Other parameters included blood pressure, heart rate, dry body weight, and a routine laboratory investigation. RESULTS: The HTEMS led to a significant improvement in all five neuropathic symptoms, and to a significant reduction in sleep disturbances for both diabetic and uremic PPN. The response was independent of the patient's age, with a responder rate of 73%. The improvement of neuropathy was time-dependent, with the best results achieved after 3 months of treatment. The HTEMS was well-tolerated by nearly all patients. CONCLUSIONS: This pilot study shows for the first time that HTEMS can ameliorate the discomfort and pain associated with both diabetic and uremic PPN in MHD patients, and could be a valuable supplement in the treatment of pain and neuropathic discomfort in patients who do not respond to, or are unable to participate in, exercise programs during hemodialysis treatment.

Prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients--the Campania Dialysis Registry.

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 (>6 months) hemodialysis patients aged 25-84. Data collection included years of dialysis, hours of dialysis/wk, disease causing hemodialysis, body mass index (BMI), erythropoietin (EPO) treatment, hemoglobin, markers of viral hepatitis, serum albumin, calcium, and phosphorus. RESULTS: Prevalence was 88.7% for anemia (hemoglobin <11 g/100 mL and EPO treatment at any Hb level), 39.4% for uncontrolled anemia (hemoglobin<11 g/100 mL). Gender, years of dialysis, hereditary cystic kidney disease (HCKD), and low BMI (<24 kg/m2) were independent correlates of anemia (P<0.001). Gender, HCKD, low BMI, serum albumin and calcium were independent correlates of uncontrolled anemia (P<0.05). An interaction was found between age (not correlated with anemia and uncontrolled anemia) and the association of gender with uncontrolled anemia (P<0.05). EPO doses were higher in patients with high prevalence of uncontrolled anemia than in patients with low prevalence (i.e., women vs men, other diseases vs HCKD, low vs not-low BMI, P<0.01). Gender, years of dialysis, HCKD, BMI, serum albumin, and calcium were independent correlates of the hemoglobin/EPO dose ratio in patients on EPO treatment (P<0.05). CONCLUSION: Anemia and uncontrolled anemia are more frequent in hemodialysis patients with shortterm 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.

Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease.

Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day), and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110 consecutive patients; after run-in, they were invited to start VLPD. Thirty subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group). At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day, respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs (from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32 to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270, P<0.0001), BP results independently related to urinary sodium excretion (P=0.023) and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in moderate to advanced CKD, VLPD has an antihypertensive effect likely due to reduction of salt intake, type of proteins, and ketoanalogs supplementation, independent of actual protein intake.

Fourteen years of hemodialysis with a central venous catheter: mechanical long-term complications.

The ideal dialysis access ensures adequate blood flow for dialysis, has a long life, and is associated with a low complication rate. Although no current type of access fulfills all these criteria, the native arteriovenous fistula (AVF) is close to doing so. Unfortunately, various kinds of vascular access (VA) are becoming more and more necessary to enable hemodialysis (HD). The central venous catheter (CVC), which is associated with higher morbidity and mortality, could be the only viable option to maintain permanent VA. We report an unusual complication in a patient, a 74-year-old female, who had been undergoing HD via a CVC for 14 yrs. A polyurethane CVC with a double lumen was inserted into the right internal jugular vein because an AVF was not feasible, and a polytetrafluoroethylene (PTFE) prosthesis was obstructed. In 2003, the CVC was removed due to stenosis and occlusion of the superior vena cava. A new CVC, also made of polyurethane and with a double lumen, was inserted into the left femoral vein. In January 2005, the patient reported a small rupture of about 3-4 mm located under the cuff of the CVC. For this reason, the left femoral vein had to be used, replacing the Optiflow one with a 40-cm long Tesio CVC, and the second catheter was inserted into the right femoral artery by conventional surgery. After 10 months, the patient returned once more, after the CVC in the left femoral vein had been removed because of malfunction and that the at-tempts to cannulate the same vein again had failed. Currently, two 70-cm long Tesio catheters implanted in the right femoral vein (whose tips almost reach the diaphragm) are used for dialysis sessions. The number of CVC implants has progressively increased amongst HD patients who are elderly, diabetic or who have been on long-term HD. The patient described in this case report is currently using a 70-cm long double Tesio catheter (single Tesio CVC in SPI silicon) placed in the right femoral vein. She has resumed therapy with dicumarol anticoagulants, maintaining INR within the 2.5-3.5 range. In conclusion, both the increase in the use of venous catheters for HD and in the survival of dialysis patients contribute towards the observation of rare complications associated with CVC use.

Global approach to cardiovascular risk in chronic kidney disease: reality and opportunities for intervention.

The current implementation into nephrology clinical practice of guidelines on treatment of cardiovascular (CV) risk factors in chronic kidney disease (CKD) is unknown. We designed a cross-sectional analysis to evaluate the prevalence and treatment of eight modifiable CV risk factors in 1058 predialysis CKD patients (stage 3: n=486; stage 4: n=430, stage 5: n=142) followed for at least 1 year in 26 Italian renal clinics. The median nephrology follow-up was 37 months (range: 12-391 months). From stages 3 to 5, hypertension was the main complication (89, 87, and 87%), whereas smoking, high calcium-phosphate product and malnutrition were uncommon. The prevalence of proteinuria (25, 38, and 58%), anemia (16, 32, and 51%) and left ventricular hypertrophy (51, 55, and 64%) significantly increased, while hypercholesterolemia was less frequent in stage 5 (49%) than in stages 4 and 3 (59%). The vast majority of patients received multidrug antihypertensive therapy including inhibitors of renin-angiotensin system; conversely, diuretic treatment was consistently inadequate for both frequency and dose despite scarce implementation of low salt diet (19%). Statins were not prescribed in most hypercholesterolemics (78%), and epoietin treatment was largely overlooked in anemics (78%). The adjusted risk for having a higher number of uncontrolled risk factors rose in the presence of diabetes (odds ratio 1.29, 95% confidence interval 1.00-1.66), history of CV disease (odds ratio 1.48, 95% confidence interval 1.15-1.90) and CKD stages 4 and 5 (odds ratio 1.75, 95% confidence interval 1.37-2.22 and odds ratio 2.85, 95% confidence interval 2.01-4.04, respectively). In the tertiary care of CKD, treatment of hypertension is largely inadequate, whereas therapy of anemia and dyslipidemia is frequently omitted. The risk of not achieving therapeutic targets is higher in patients with diabetes, CV disease and more advanced CKD.

[Bioelectrical analysis in uremic patients]. / La bioimpedenza nella clinica del paziente uremico.

Bioelectrical analysis (BIA) is an easy, repeatable, low cost, operator-independent method. BIA obtains two different goals, i.e. body water content evaluation, by the RXc Graph or the BIVA Z score and morbidity and mortality predictions by the phase angle. Therefore, BIA can be considered as part of the clinical examination for the evaluation of both hydration and nutritional status.

Sleep disorders in hemodialyzed patients--the role of comorbidities.

BACKGROUND: Sleep disorders are very frequent in hemodialyzed patients, but the relationship between these disorders and water withdrawal, urea removal and comorbidities has not been sufficiently clarified. METHODS: The study comprised a group of 88 patients in good nutritional condition, with target hemoglobin concentration, good control of blood pressure and optimal dry weight. After answering a questionnaire (SDQ) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) patients were assigned to one of 3 groups: those with no disturbances (no.20), those with subclinical disorders (n.35) and insomniacs (n.33). Yearly fluid and urea withdrawal by dialysis and the Charlson Comorbity Index were measured. RESULTS: Sleep disorders were observed in 77.27% of the patients. There was no difference in body fluid and urea withdrawal between groups. In the group of patients with no sleeping disturbances, the Charlson Comorbidity Index was significantly lower (p<0.001) than in patients with subclinical disorders or insomnia and emerged as a strongly associated with sleep disturbances. The study also attributes a predictive role to age, dialytic age, dialysis shift, antihypertensive drugs. The data indicate that, in evaluating sleeping disorders in patients on maintenance hemodialysis, comorbidities should be assessed.

[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

Charlson Comorbidity Index is a predictor of outcomes in incident hemodialysis patients and correlates with phase angle and hospitalization.

BACKGROUND: The adjustment of comorbidity is important in international hemodialysis comparisons. The aim of this study is to verify if it is possible to use the Charlson Comorbidity Index (CCI), in an Italian population of incident hemodialysis patients from the Campania region as outcome predictors. A similar proposal has already been made for an American population of incident patients in peritoneal dialysis. METHODS: The data for this study come from the Uremic Registry of Campania taken in the year 2001. This is an observational study in which demographic, comorbid, laboratory, treatment and insurance data were collected in 111 dialysis units (70%) in Campania. We evaluated 515 hemodialysis incident patients who were hemodialyzed in Campania between January 1 and December 31, 2001. The study was restricted to patients who had already undergone 90 days of hemodialysis. The duration of this study was 15 months. Charlson Comorbidity Index was performed. In 128 patients (24.8%) BIA measurements were performed after dialysis. STATISTICS: We used Student's t test for unpaired data and Cox proportional model to analyze predictors of mortality. The variables analyzed were age at start of hemodialysis, sex, CCI, hemoglobin, diabetes, hypertension, albumin, days of hospitalization. The statistically significant variables, analyzed initially by univariate analysis, were chosen for multivariate analysis. We considered p < 0.05 statistically significant. RESULTS: A total of 515 patients (M = 316, F = 199) (age: 63.62 +/- 15.35 years) presented with the following diseases: NO diagnosed in 93 patients (19%), GN in 64 (13%) IN in 42 (99%), Hereditary in 55 (11%), Vascular in 66 (14%), Diabetes in 135 (28%), others in 30 (6%). Hemoglobin levels were 10.71 +/- 1.51 g/dL and albumin was 3.79 +/- 0.54 g/dL. The days of hospitalization for the population studied were 3364/year. After the study, 75 patients died and the overall mortality rate was 11.65/100 patient/years. Univariate analysis shows that there are significant differences calculated for age (median value 73 and 65 years, respectively for non-survivers and survivers), BMI (median value and 22 and 24 kg/m2, respectively), Hb (median value 9.5 and 11 g/dL, respectively), Albumin (median value 3.5 and 3.8 g/dL, respectively), days of hospitalization (median value 8 and zero days, respectively), CCI (median value 6 and 4 score, respectively, phase angle (median value 3.3 and 4 degree, respectively). The mortality rates (100 dialysis years) by the CCI score: the mortality rate was zero for patients with a CCI of 3; and it increased to approximately 60% of patient years with a CCI score of 6 or greater. The linear correlation between CCI and phase angle in living (y = 18.90 x -3.83; R2 = 0.56) and in the dead (y = 13.01 x -1.87; R2 = 0.29). DISCUSSION: We found that CCI is a strong predictor of mortality in incident HD patients as has also been indicated in PD patients; CCI correlates with phase angle calculated from Bioelectrical Impedance Analysis and this last factor can be used in the following examinations; several days of hospitalization are a very important determinant in the survival in hemodialysis patients.

The prediction of single-frequency BIA variables from individual characteristics.

To define whether reference values for bioimpedance analysis (BIA) can be predicted in healthy individuals, individual characteristics and BIA variables (resistance index=height(2)/parallel resistance and reactance index= height(2)/parallel reactance) were evaluated in non-obese healthy individuals: 863 men and 769 women with an age range 20-70 years and body mass index (BMI) 19.0-29.9 kg/m(2). The following predictive equations were obtained using multiple regression analysis:Resistance index (cm(2)/ohm)Males 21.06 + 0.087xage + 1.091xweight -1.801xBMI,Females 20.35 + 0.037xage + 0.878xweight - 1.343xBMIReactance index (cm(2)/ohm)Males 0.57 + 0.117xweight - 0.096xBMIFemales 1.42 + 0.078xweight - 0.075xBMIIn conclusion, reference BIA values seem to be reasonably predicted based on individual characteristics.

[The optimization of the treatment and timing of the intervention by a nephrologist in pre-dialytic chronic renal insufficiency]. / L'ottimizzazione delle cure e il "timing" dell'intervento del nefrologo nell'insufficienza renale cronica pre-dialitica.

BACKGROUND: Early referral to nephrologists of patients with chronic renal failure (CRF) reduces morbidity and mortality in dialysis. Aim of this work is to evaluate the condition of early and late referral, and whether the two different conditions can affect the treatments. MATERIALS AND METHODS: This is a prospective study with a 12-month follow-up period. During this time, we verified the prevalence of patients with serum creatinine > 1.5 mg/dL (CRF patients) and the condition of early or late referral, defined as referral to nephrologists for > or < 3 times during follow up, respectively. Diagnosis of diabetes mellitus and/or arterial hypertension, and the use of antihypertensive drugs, insulin, hypoproteic diet and erythropoietin was recorded in each patient. RESULTS: CRF (mean serum creatinine value = 2.11+/-1.52 mg/dL) was observed in 190 patients aged 72.05+/-11.62 years. The prevalence of CRF was 4718 pmp. Diabetes and hypertension were diagnosed in 107 subjects (56.3%) and 152 subjects (80%), respectively. Only 74.2% (no. 141) of the patients with CRF was habitually followed by the nephrologist and the frequency was directly correlated to the degree of CRF: 100% of the patients with Creatinine Clearance (Cr Cl) < 25 mL/min, 70% with Cr Cl >25 < 50, and 0% with Cr Cl >50 < 80 mL/min. Early referral was coupled with a wider use of a hypoproteic diet, erythropietin, and the association ACE-I + Angiotensin II receptor antagonists. CONCLUSION: In conclusion, our data show a prevalence of CRF that is at least 5 times greater than that of dialysis patients. The condition of late referral is present in about 30% of the CRF population from the time of the initial phases of renal disease. Referral time affects the modalities of the treatment.

[Daily nutrient intake in hemodialysis]. / Variabilità dell'introito giornaliero di nutrienti nei pazienti emodializzati.

BACKGROUND: Although there is a higher nutrient requirement, food intake in haemodialysis patients is often inadequate. Protein nitrogen appearance (PNA) indirectly estimates the mean protein intake during the short interdialysis period, but it does not measure the daily nutrient intake, which is generally unknown. We carried out a longitudinal study aimed at estimating the daily nutrient intake and its relationship with the nutritional status of haemodialysis patients. METHODS: We selected 28 haemodialysis patients with adequate nutritional status and no evidence of risk-factor for malnutrition. Patients were treated with biocompatible membranes, low-flux and high bicarbonate dialysis, Kt/V > 1.2, PNA > 1.1 g/kg/day and erythropoietin. We measured every four months daily PNA, protein and calorie intake (DPI, DCI) as well as weight gain (WG) during an entire week for one-year. The nutritional status was assessed by biochemical and BIA markers. RESULTS: Twenty seven subjects (8 F, 19 M; age 57.1 +- 2.7 yeas; dialysis age 105 +- 13 months) completed the trial. The mean interdialytic PNA did not change in both long- and short-interdialysis periods, resulting in the "normal" range (> 1.1 g/kg/day); however, daily levels of protein and calorie intake were significantly reduced on the third day during the long interdialysis interval. Eight patients showed time-averaged values of DPI and DCI lower than 0.8 g/kg/day and 25 Kcal/kg/day, respectively, on the third day (LOW group), values that were associated with similar changes in WG. Such a highly reduced nutrient intake during the third interdialysis day was associated with a normal PNA value (1.23 +- 0.05 g/kg/day vs 1.30 +- 0.06 in CON, NS) when measured during the short interdialysis period (S), just as it is in clinical practice; in contrast, when the PNA value was measured during the long interdialysis period it was found to be significantly reduced (1.07 +- 0.08 g/kg/day vs 1.37 +- 0.06 in CON, p < 0.05 and vs S, p < 0.05). During the study, the body weight progressively decreased from 68.0 +- 5.5 to 65.8 +- 5.9 kg (p < 0.05) in the LOW group, due to the decrease in lean body mass, as suggested by the reduction in serum creatinine (9.2 +- 1.1 vs 8.1 +- 0.7 mg/dL, p < 0.05), creatinine generation (835 +- 155 vs 723 +- 106 mg/die, p < 0.05) and serum albumin (3.96 +- 0.07 vs 3.66 +- 0.06 g/dL, p < 0.05). Moreover, reactance and phase angle declined in the LOW group (from 54 +- 4 to 44 +- 3 ohms, p < 0.05 and 5.5 +- 0.3 to 4.5 +- 0.3 degrees, p < 0.05, respectively). At the end of the study the nutritional status in the LOW group was reduced as compared to the CON group. CONCLUSIONS: In stable, well-nourished haemodialysis patients, in absence of known risk factors for malnutrition, the daily nutrient intake is variable and progressively reduce during the interdialytic interval. The measurement of interdialytic PNA, as is done in clinical practice, does not enable the discovery of such abnormal eating behaviour; the low daily nutrient intake, on the contrary, can be evidenced by the daily measurement of either PNA or weight gain, and it can also be inferred by the reduced PNA during the long interdialytic period. Finally, the persistent reduction in nutrient intake below the threshold of 0.8 g/kg/day of proteins and 25 Kcal/kg/day one day a week, is capable of inducing body protein wasting and moderate impairment of the nutritional status.

[Can anemia be corrected in hemodialysis patients with thalassaemia minor? ]. / La correzione dell'anemia nei pazienti in emodialisi con Talassemia minor e' possibile?

BACKGROUND: Anemia is an important negative prognostic factor for dialysis patients, whose correction reduces hospitalisation and mortality. Besides, the presence of the thalassaemia minor (Thal-m) in haemodialysed patients causes erythropoietin resistance and more serious anemia. The goal of this study is the correction of anemia (Hb >11 g/dL) in haemodialysed Thal-m patients. MATERIALS AND METHODS: Multicentric, prospective and controlled 12-month study for the correction of anemia (up to values ranging from 11 to 12 g/dL) followed by a 12-month observation period. Ten Thal-m patients with inadequate anemia correction were studied after therapy with rHuEPO. Their age at the beginning of the study was 62.8+/-4 years while their dialytic age was 89+/-20 months. RESULTS: During the study we observed no changes in dry weight (p=NS), no increase in interdialytic weight (p=NS), cardiac frequency (p=NS), serum albumin (p=NS), serum aluminium (p=NS), PTH (p=NS), URR (p=NS), flow FAV (p=NS), TSAT (p=NS) and ferritin (p=NS) (maintained at their optimal values by means of intravenous therapy with trivalent iron. The hypotensive therapy (1.6 drug/patient/year) required no modifications during the 24-month study. The rHuEPO dose varied from 200.3+/-94.3 to 286.6+/-116.2, 317.0+/-119.5, 446.9+/-142.3, and 407.0+/-130.5 U/kg/wk (p < 0.0001 vs. initial value) (from the start to the 3rd, 6th, 9th and 12th month, respectively). The dose was subsequently reduced to 385.2+/-119.7 U/kg/wk at 15 months (p < 0.0001 vs. initial value) and remained unchanged until the end of the study. Simultaneously, the Hb values at corresponding times were 9.2+/-0.9, 9.4+/-1.1, 10.2+/-1.4, 10.9+/-1.5, 11.2+/-1.4 and 11.0+/-1.4 (p=0.002 vs. initial value). The correction of anemia produced progressive reduction in cardiac mass from 141+/-12 to 120+/-10 and 110+/-8 g/mq at the beginning, 12th month and 24th month (p < 0.0001), respectively. During the study the hospitalisation time was 4.3+/-1.2 day/patient/year during the 3-month run-in period, 3.4+/-1.4 day/patient/year during the first year, and 3.1+/-1.1 day/patient/year during the second year (p=0.098). CONCLUSIONS: In conclusion we can say that the question of Thal-m in dialysis patients cannot be ignored or underestimated. The rHuEPO dosage in these patients must be reassessed (a dose of 450 U/kg/wk corresponding to approximately 60,000 units/week is acceptable and does not produce an increase in side effects if the correction is done gradually); moreover, other factors responsible for EPO-resistance must be eliminated (hyperthyroidism, aluminium intoxication, iron overloaded or deficiency).