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.

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.

[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.

[Thalassaemia minor: national survey of uraemic patients under substitutive treatment]. / Talassemia minor: indagine nazionale dei pazienti uremici in trattamento sostitutivo.

BACKGROUND: The incidence of thalassaemia minor in end-stage renal disease patients is similar to that of the general population. Both these conditions are characterized by anaemia, but the underlying pathophysiology is quite different. Current literature lacks an adequate clinical survey of haemodialysis patients with thalassaemia minor. METHODS: The prevalence of thalassaemia minor (thal-m) in haemodialysis patients was assessed by a national survey collecting general information as well as clinical and haematological parameters. Data were also collected on the use of recombinant erythropoietin in these subjects. A dedicated questionnaire was sent to all Italian dialysis units. RESULTS: Only 116/705 dialysis units returned the questionnaire (16.4%): 33 units did not have any patients affected by thalassaemia minor. No response was obtained from six Italian regions whereas ten regions returned only partial answers. The response from four regions was satisfactory (20%) while the completed questionnaire was returned by all units in only two small regions. A total of 7731 ESRD patients were collected, 240 (3.1%) were also affected by thal-m, 142 males and 98 females. In the four regions with the highest response rates, Calabria 45%, Puglia 65%, Basilicata and Molise 100%, the prevalence of thal-m were 3.68%, 4.56%, 3.3% and 1%, respectively. A total of 3623 uraemic patients (47% of all enrolled subjects) were collected from these four regions. Here is the patient geographic distribution: northern Italy 2.16% (response rate of 9.44%); central Italy 1.69% (response rate of 7.64%), southern Italy 3.77% (response rate of 29.46%). The age range of thal-m patients was 17 to 90 years, the time spent on dialysis was between 3 and 384 months, the body weight was between 35 and 93 kg, the Hb value was between 6.2 and 13.6 g/dl, and the Htc value was between 19 and 44%. A total of 230 thal-m patients were on haemodialysis while 10 patients were on peritoneal dialysis (4.2%). The mean haemoglobin level for the thal-m group was 9.8+/-1.4 g/dl and for the control group the value was 11.4+/-1.4 g/dl (p < 0.0001). The use of rhEPO was on the average 7659+/-6256 u/wk for the thal-m and 4378+/-4435 u/wk for the control group (p < 0.0001). The bodyweight was 129+/-105 u/kg/wk (range 0-370). Finally, 17.9% of the thal-m patient did not use rhEPO, their Hb value was 10.66+/-1.67 g/dl (range 8.2-13). No patient went over 30 thousand units and only 4 had such dosage in therapy. The 12.1% thal-m patients with Hb < 10 g/dl did not use rhEPO. The need for rhEPO per gram of Hb was 796+/-722 u/wk in thal-m patients and 416+/-449 U/wk in control patients (p < 0.0001). Uraemic anaemia was corrected with 4.8 million red blood cells in the control group and with about 7.7 million red blood cells in the thal-m group. CONCLUSIONS: Data from this national survey, although incomplete, show that rHuEpo is less effective in these patients and its use does not seems to be correct. It is important to emphasise that recent Guidelines do not recommend neither a specific treatment for these patients nor the use of r-HuEpo. However, it should also be underscored that most thal-m patients do not reach the target Hb level suggested by the National Guidelines for the general population in chronic dialysis.

Bioelectrical impedance measurement: errors and artifacts.

Bioelectrical impedance analysis (BIA) allows simple noninvasive estimation of body water, and it could potentially be a very useful technique for clinical monitoring and study of abnormalities of body water. It has been shown that the total body impedance is dominated by the arm (46%) and leg (44%). The trunk, which represents an average of 46% of the body weight, accounts for only 10% of the total impedance. The objective of the current study was to determine the errors in prediction of body composition from BIA when applied to dialysis patients with measurement on the nondominant arm, postural changes, muscular contractions or cramps, monolateral lymphoedema, arteriovenous fistula, central venous catheter, or vascular graft. We studied 20 healthy subjects, 20 uremics on chronic hemodialysis, 3 uremics with fever (body temperature >38.5 degrees C), 3 uremics with cramps, 3 patients with monolateral lymphoedema of an arm, and 3 patients with a prosthetic fistula on an arm. The results of our study show different values of total body water (TBW) derived by BIA measurements effected on supine or standing position (percentage rate variation = 1.1% to 1.6%), or effected during fever (6%), during cramps (-0.73%), with lymphoedema (25%), or in presence of a native arteriovenous fistula, a catheter in a central vein, or a graft (between -24% and +4%). We concluded that a significant error may occur in the measurement of body composition from whole body BIA when performed in the reported cases.