Insomnia in diabetic hemodialysis patients. Prevalence and risk factors by a multicenter study

BACKGROUND: Insomnia is one of the most common problems in dialysis patients, and likely to contribute impairment in quality of life, which has a positive correlation with patients' survival. In diabetic patients, morbidity and mortality are substantially higher than in the nondiabetic counterparts, and also the incidence of sleep disturbances. However, there is no means to predict sleep disturbance in the dialysis patients especially in diabetics. To define the prevalence and risk factors for insomnia in diabetic patients on hemodialysis, we undertook a cross-sectional multicenter study. METHODS: Eighty-two diabetic patients (50 men/32 women, aged 58.7 +/- 9.23 years) on maintenance hemodialysis for more than 6 months from 12 different hospitals were enrolled. The demographic data, subjective symptoms, depression scale, and insomnia were assessed by questionnaires, and lean body mass, BMI, Kt/V, subjective global assessment, nursing assessment score (NAS), and biochemical parameters were examined. RESULTS: The number of patients with and without insomnia were 56 and 26, respectively, which amounted to 68.2% for insomnia. NAS (28.1 +/- 3.81 vs. 30.8 +/- 2.88, p = 0.002), serum albumin concentration (3.82 +/- 0.44 vs. 4.09 +/- 0.36 g/dl, p = 0.008), and depression scale (25.2 +/- 12.1 vs. 18.9 +/- 10.3, p = 0.025) were significantly different between them. Patients with insomnia were older (60.5 +/- 9.0 vs. 56. 1 +/- 9.60 years, p = 0.053) and felt pain (38.5 vs. 15.3%, p = 0.06) more frequently than those without insomnia. The scale of depression was correlated with NAS (r = -0.455, p < 0.001) and the serum albumin concentration was correlated with NAS (r = 0.337, p = 0.002). NAS, age, and serum albumin concentration were the major risk factors for insomnia in logistic regression analysis. CONCLUSION: The prevalence of insomnia in diabetic hemodialysis patients was 68.2%. Age, nutritional status, and depression were the major risk factors for sleep disturbance in diabetic patients.     

The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients.

BACKGROUND: The benefits of residual renal function (RRF) in peritoneal dialysis patients have been described frequently. However, previous reports have shown that RRF diminished faster in haemodialysis (HD) patients than in peritoneal dialysis patients, and in most of the studies in HD patients, RRF was ignored. In this study, the RRF in chronic HD patients was studied to assess its impact on patients' nutritional status. METHODS: In 41 chronic HD patients with at least a 2-year history of HD treatment, RRF was determined by a urine collection for 7 consecutive days. Nutritional parameters, such as percentage body fat, fat-free mass index, serum albumin concentration and normalized protein catabolic rate, were also measured. RESULTS: In all 41 patients, mean weekly total Kt/V urea was 4.88 and renal Kt/V urea was 0.65. RRF was well correlated with serum albumin concentration, but dialysis Kt/V urea was not. One year after the start of this study, RRF and nutritional indices were re-examined and patients were classified into two groups: with RRF, preserved residual renal diuresis over 200 ml/day (mean, 720 ml; range, 230-1640 ml), N=23; and without RRF, persistent anuria (mean, 51 ml; range, 0-190 ml), N=18. At the start of this study, the mean serum albumin concentration and mean normalized protein catabolic rate in patients with RRF were 3.84 g/dl and 1.16 g/kg/day, respectively, which were significantly higher than those in patients without RRF (P=0.02 and P=0.0002, respectively), despite total (renal+dialysis) Kt/V urea being equal in both groups. During the 1-year study period, there was no significant change in total Kt/V urea in either group. Mean serum albumin concentration increased to 4.05 g/dl in patients with RRF, but did not change significantly (from 3.66 to 3.62 g/dl) in patients without RRF. The same trend was observed in all other parameters. CONCLUSION: Over half of our HD patients had sufficient RRF. RRF itself may have a beneficial effect on nutritional parameters, and it is important to determine RRF over time, even in chronic HD patients.     

Effect of prescribing a high protein diet and increasing the dose of dialysis on nutrition in stable chronic haemodialysis patients: a randomized, controlled trial.

BACKGROUND: Protein requirements in stable, adequately dialysed haemodialysis patients are not known and recommendations vary. It is not known whether increasing the dialysis dose above the accepted adequate level has a favourable effect on nutrition. The aim of this study was to determine whether prescribing a high protein diet and increasing the dose of dialysis would have a favourable effect on dietary protein intake and nutritional status in stable, adequately dialysed haemodialysis patients. Effects on hyperphosphataemia and acidosis were also studied. METHODS: Patients were randomized to a high dialysis dose (HDD) group (target Kt/V(eq) of 1.4) or a regular dialysis dose (RDD) group (target Kt/V(eq) of 1.0). All patients were prescribed a high protein (HP) diet [1.3 g/kg of ideal body weight (IBW)/day] and a regular protein (RP) diet (0.9 g/kg/day), each during 40 weeks in a crossover design. In 50 patients, 23 in the HDD and 27 in the RDD group follow-up was > or =10 weeks. These patients, aged 56+/-15 years, were included in the analysis. Nutritional status was assessed by anthropometry, plasma albumin and a nutritional index. RESULTS: Delivered Kt/V(eq) in the HDD group (1.26+/-0.14) was significantly higher than in the RDD group (1.02+/-0.08). Protein intake estimated from total nitrogen appearance (PNA) measurements and food records (DPI) was significantly higher during the HP diet (PNA(IBW), 1.01+/-0.18 g/kg/day; DPI(IBW), 1.15+/-0.18 g/kg/day) than during the RP diet (PNA(IBW), 0.90+/-0.14 g/kg/day; DPI(IBW), 0.94+/-0.11 g/kg/day). Increasing the dialysis dose did not increase protein intake either during the HP or RP diet. Plasma albumin (41.9+/-3.0 g/l) lean body mass (107+/-15% of normal values) and the nutritional index did not differ between the dialysis dose groups or protein diets and remained stable overtime. Dry body weight (97+/-14%) and total fat mass increased over time in the HDD group, but remained stable in the RDD group suggesting an effect of dialysis dose on energy balance. There was no effect of the protein diets on dry body weight or total fat mass. Plasma phosphate levels and oral bicarbonate supplements were lower in the HDD group, but were comparable between the protein diets. CONCLUSIONS: Prescribing a HP diet resulted in a modest increase in actual protein intake, but increasing dialysis dose did not have a contributing effect. A HP diet or increasing the dialysis dose did not have a favourable effect on the nutritional status. A dietary protein intake of at least 0.9 g/kg IBW/day appears to be sufficient for adequately dialysed haemodialysis patients without overt malnutrition.     

The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes

The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes. We performed a case-control study aiming to evaluate the association between the Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104 type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on dialysis and 26 with proteinuria [AER >or=200 microg/min] and serum creatinine >or=2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 microg/min) with known diabetes duration >or=10 years (control subjects). The genotypic distribution of the PPARgamma2 Pro12Ala polymorphism in these diabetic patients was in Hardy-Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1% males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 +/- 10 vs. 61 +/- 10 years), known diabetes duration (17 +/- 7 vs. 16 +/- 7 years), BMI (27 +/- 4 vs. 28 +/- 5 kg/m(2)), fasting plasma glucose (184 +/- 81 vs. 176 +/- 72 mg/dl), HbA(1c) (6.7 +/- 2.3 vs. 6.9 +/- 2.4%; high-performance liquid chromatography reference range: 2.7-4.3%), and systolic (145 +/- 27 vs. 0.144 +/- 24 mmHg) or diastolic (87 +/- 14 vs. 85 +/- 14 mmHg) blood pressure, respectively. In conclusion, the presence of the Ala allele may confer protection from diabetic nephropathy in patients with type 2 diabetes.     

Malnutrition in hemodialysis diabetic patients: evaluation and prognostic influence

BACKGROUND: This work aimed to evaluate the role of malnutrition in the increased mortality rate of hemodialysis diabetic patients from a French cooperative series. METHODS: Body mass index (BMI), serum albumin, prealbumin, cholesterol, and pre-dialysis creatinine, normalized protein catabolic rate and lean body mass (LBM) were measured in 734 diabetic and 6389 non-diabetic patients (aged 63.4 +/- 12.2 and 62.0 +/- 15.9 years; 1.01 male to 1.40 female ratio). The outcome of 1610 of these patients, including 170 diabetics, was assessed during a 30-month follow-up. RESULTS: Diabetic as compared to non-diabetic patients showed a significant (P < 10-4) increased BMI (25.9 +/- 5.2 vs. 23.1 +/- 4.3) and cholesterol (5.5 +/- 1.6 vs. 5.3 +/- 1.5 mmol/L), and decreased albumin (37.8 +/- 5.4 vs. 38.9 +/- 5.3 g/L), prealbumin (317 +/- 91 vs. 340 +/- 94 mg/L), creatinine (711 +/- 184 vs. 816 +/- 217 micromol/L) and LBM (76 +/- 18 vs. 87 +/- 21%). Normalized protein catabolic rate was similar in the two groups (1.11 +/- 0.31 vs. 1.13 +/- 0.32 g/kg/L). One and two-year survival was 83.7 +/- 2.9% and 65.5 +/- 3.8% in diabetic patients versus 90.3 +/- 0.8% and 79.9 +/- 1.1% in non-diabetics (relative risk 1.26, P < 0.01). Independent predictors of survival were age, albumin and prealbumin in non-diabetics and only age in diabetics. CONCLUSION: Diabetic patients compared to non-diabetics were characterized by an increased incidence of protein malnutrition and decreased survival. However, the higher death risk associated with diabetes was not related to malnutrition.     

Aortic calcification in haemodialysis patients with diabetes mellitus.

BACKGROUND: Certain metabolic disorders, such as hyperphosphatemia induce vascular calcification in haemodialysis patients; it is unclear, however, whether these disorders contribute to aortic calcification in diabetic haemodialysis patients. This study examined the risk factors of aortic calcification in a large number of haemodialysis patients, and compared risk factors between diabetic and non-diabetic patients. METHODS: The subjects were 667 patients on maintenance haemodialysis: 184 with type 2 diabetes and 483 without. Aortic calcification was measured semi-quantitatively using a plain computed tomography image of the abdominal aorta, and an aortic calcification index (ACI) was calculated. RESULTS: The ACI of the diabetic subjects was significantly higher than that of those without diabetes (57.3+/-22.1 vs 44.8+/-28.3%, P < 0.0001), although the dialysis vintage of the former was significantly shorter (P < 0.001). Multiple regression analyses showed that diabetes was a significant independent risk factor for increased ACI. Multiple regression analyses, performed separately in diabetics and non-diabetics, revealed that advanced age, higher systolic blood pressure, smoking and longer haemodialysis vintage were common independent risk factors significantly associated with increased ACI in both patient groups (R2 = 0.296, P < 0.0001 for non-diabetics; R2 = 0.193, P < 0.0001 for diabetics). Higher serum phosphate concentration was not significantly associated with increased ACI in diabetic patients (P = 0.429), although it was a significant independent factor in non-diabetic patients (beta = 0.150, P < 0.0005). CONCLUSION: Aortic calcification in diabetic haemodialysis patients is more advanced, compared with non-diabetic patients, even with short haemodialysis vintage. Since disorders of mineral metabolism are not significantly associated with aortic calcification in diabetic haemodialysis patients, aortic calcification in these patients could be affected by metabolic abnormalities associated with the diabetic state per se, independent of other confounding factors; and aortic calcification may be advanced even before haemodialysis induction.     

The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients

One of the main causes of protein-energy malnutrition in patients on maintenance hemodialysis (MHD) is metabolic acidosis. The aim of this study was to evaluate the effect of metabolic acidosis on nutritional status in a group of MHD patients with adequately delivered dialysis treatment. Of 165 eligible anuric MHD outpatients with Kt/V ≥ 1 and no underlying inflammatory diseases, 47 subjects were enrolled. In order to evaluate the effect of different parameters on serum albumin, we measured the pre-dialysis serum albumin, blood pH, serum bicarbonate (HCO 3￣ ), Kt/V, normalized protein catabolic rate (nPCR) and body mass index (BMI) in these patients. The mean age of the study patients was 55 ± 13.8 years; there were 22 females and six diabetics. The average Kt/V was 1.22 ± 0.16, pH was 7.40 ± 0.15, serum HCO 3￣ was 23.18 ± 2.38 mEq/L, serum albumin was 4.03 ± 0.56 g/dL, nPCR was 1.00 ± 0.16 g/kg/day, post-dialysis body weight was 58.50 ± 11.50 kg and BMI was 23.47 ± 2.70 kg/m 2 . There was a statistically significant direct correlation between serum albumin and BMI (r = 0.415, P = 0.004), and between serum albumin and serum HCO 3 (r = 0.341, P = 0.019). On multiple regression analysis, the predictors of serum albumin were serum HCO3￣ and BMI (direct effect) and nPCR (inverse effect). In 17 patients on MHD with serum HCO3￣ <22 mEq/L, there was a significant inverse correlation between HCO 3 and nPCR (r = 0.492, P = 0.045), and these patients had significantly lower serum albumin compared with patients with serum HCO3￣ >22 mEq/L (P = 0.046). These data demonstrate that patients on MHD with metabolic acidosis had a lower serum albumin concentration despite adequate dialysis treatment. The inverse effect of nPCR on serum albumin concentration in acidotic MHD patients may be due to hypercatabolism in the setting of metabolic acidosis, leading to deleterious effects on the nutritional status of patients on MHD.     

Acidosis and nutritional status in hemodialyzed patients. French Study Group for Nutrition in Dialysis

In a cross-sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end-stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre- and postbicarbonate-dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (+/- 1 SD) were age 61 +/- 16 years, BMI 23.3 +/- 4.6 kg/m2, dialysis time 12.4 +/- 2.7 h/week, HCO3 22.8 +/- 3.5 mmol/L, albumin 38.7 +/- 5.3 g/L, prealbumin 340 +/- 90 mg/L, Kt/V 1.36 +/- 0.36, nPCR 1.13 +/- 0.32 g/kg BW/day, and LBM 0.86 +/- 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16-30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted between bicarbonate and Kt/V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.     

Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters.

BACKGROUND: Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality. METHODS: Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months. RESULTS: There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups. CONCLUSIONS: Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients.     

Importance of dialysis adequacy in mortality and morbidity of chinese CAPD patients

BACKGROUND: In continuous ambulatory peritoneal dialysis (CAPD), the impact of dialysis adequacy on patient outcome is well established in Caucasian patients but is less clear in Asian patients. Recent evidence suggests that Asian dialysis patients enjoy better overall survival. We hypothesize that dialysis adequacy may be less important in determining outcome for this ethnic group. METHODS: We performed a single-center prospective observational study. From September 1995, we enrolled 150 existing and 120 new CAPD patients. They were followed for up to three years. We monitored dialysis adequacy and nutritional indices, including Kt/V, weekly creatinine clearance (CCr), residual glomerular filtration rate (GFR), normalized protein catabolic rate (NPCR), percentage of lean body mass (%LBM), and plasma albumin level. Clinical outcomes included mortality, technique failure, and duration of hospitalization. RESULTS: The duration of study follow-up was 22.1 +/- 12.3 months. In our study population, 136 were male. Seventy were diabetic (25.9%), and 212 were treated with 6 L exchanges per day (78.5%). The body weight was 59.3 +/- 9.4 kg. Baseline total Kt/V was 1.78 +/- 0.41, peritoneal Kt/V 1.48 +/- 0.36, and median residual GFR 0.98 mL/min (range 0 to 7.45). Two-year patient survival was 83.0%, and technique survival was 72.8%. Multivariate analysis showed that the duration of dialysis, diabetes, %LBM, index of dialysis adequacy (Kt/V or CCr), residual GFR, and requirement of a helper for CAPD exchanges were independent factors of patient survival; serum albumin, adequacy index (Kt/V or CCr), and requirement of a helper were independent factors of technique survival. Duration of dialysis, body weight, requirement of helper, cardiovascular disease, HBsAg carrier, serum albumin, and CCr had independent effects on hospitalization. The peritoneal component of Kt/V or CCr had no independent effect on any outcome parameter. When the prevalent and new CAPD cases were analyzed separately, Kt/V predicted survival only for new CAPD cases. CONCLUSIONS: Our results show that dialysis adequacy has significant impact on outcome of Asian CAPD patients. Although we have excellent medium-term patient and technique survival, this favorable outcome should not prevent health care workers from providing adequate dialysis to Asian patients. The reason of discrepancy in outcome between Asian and Caucasian dialysis patients requires further study.     

Risk factors for higher mortality at the highest levels of spKt/V in haemodialysis patients.

BACKGROUND: The survival of patients on haemodialysis improves as the delivered doses of dialysis attain a Kt/V of 1.2 or more. However, a consistent yet paradoxical finding in the Kt/V survival relationship is that the mortality tends to increase at the higher ends of Kt/V. METHOD: To determine the relationship of Kt/V with survival at a time when increasing doses of dialysis are being delivered and to examine the effect of body mass and nutritional markers including serum pre-albumin on the paradoxical relationship, we analysed relative mortality risk (RR) as a function of single-pool Kt/V (spKt/V) in the Cox proportional hazard model. We used body mass index (BMI), dry body weight and nutritional parameters including serum pre-albumin obtained in 1151 patients on chronic haemodialysis as covariates. RESULTS: The mean spKt/V for February and March of 1997 was 1.46+/-0.28 (+/-SD). A spKt/V of >1.2 was achieved in 82.5% of patients and 20% of patients received a spKt/V of >1.68. Using spKt/V in deciles and assigning the third decile (spKt/V 1.2-1.3) as the reference group with an RR of 1, the extreme first and the tenth deciles displayed a higher RR imparting a U-shaped configuration to the curve. In this unadjusted analysis, there was no dependency between delivered dose of spKt/V and RR values. spKt/V values were re-analysed in quintiles. The U-shaped relationship persisted between spKt/V and RR, and an unadjusted analysis again exhibited no clear dependency between spKt/V and RR. The patients in the highest fifth spKt/V quintile, who received the highest dose of dialysis and had the paradoxical increase in RR, had the lowest body weight, BMI, serum pre-albumin and creatinine. Adjustments for case-mix characteristics (age, gender, race and diabetes) in the Cox multivariate model did not reduce the paradoxical increase in RR. However, introduction of BMI or dry body weight along with serum creatinine and pre-albumin to the above case-mix covariates for the first time produced a dose-dependent inverse relationship between the first four quintiles of the spKt/V and their respective RR. With the above variables adjusted, the fifth quintile RR of 1.6 (0.9, 3.1) was reduced to 0.9 (0.4, 2.0), but was not corrected to the lowest RR of 0.6 (0.2, 1.2) noted in the fifth spKt/V quintile. This difference between the adjusted RR of fifth and fourth quintile was not statistically significant, but persisted after adjusting for any clustering variation. CONCLUSIONS: Our analysis, which is the first to include serum pre-albumin in the Kt/V survival analysis, demonstrates a steeper rise in the unadjusted RR at the highest end of spKt/V levels than reported previously and suggests that patients with lower weight and nutritional parameters may mostly account for the spKt/V and RR paradox. As we find a worsening in the spKt/V-RR paradox at a time when higher doses of dialysis are being delivered, we speculate that factors other than underweight and malnutrition such as 'toxicity' of rapid dialysis, especially in sick and underweight patients, may contribute to the paradox. If future studies were to verify this possibility, sick and underweight patients could benefit from less vigorous but frequent sessions of haemodialysis.     

Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders.

BACKGROUND: Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. METHODS: We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. RESULTS: During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). CONCLUSIONS: The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.     

Effective flow performances and dialysis doses delivered with permanent catheters: a 24-month comparative study of permanent catheters versus arterio-venous vascular accesses.

BACKGROUND: Permanent venous catheters have emerged as a long-term vascular access option for renal replacement therapy in end-stage renal disease patients. The design and venous location of catheter devices bear intrinsic flow limitations that may negatively affect the adequacy of dialysis and the patient outcome. There is limited data comparing the long-term dialysis adequacy delivered with permanent catheters vs arterio-venous vascular accesses (AVA). METHODS: To explore this problem, we conducted a prospective 24-month trial comparing the flow performances and dialysis dose (Kt/Vdp) deliveries of both access options in a group of 42 haemodialysis patients during two study phases. During the first 12 months the patients completed a treatment period by means of permanent dual silicone catheters (DualKT). Then they were transferred to an AVA (40 native arterio-venous fistulas and two PTFE grafts) and monitored for an additional 12-month period. Assessments of flow adequacy and dialysis quantification were performed monthly. RESULTS: Dialysis adequacy was achieved in all cases. No patient had to be transferred prematurely to the AVA because of catheter failure. Three catheters had to be replaced due to bacteraemia in three patients. The mean effective blood flow rates achieved were 316+/-3.5 ml/min and 340+/-3.3 ml/min with DualKT and AVA, respectively, for a pre-set machine blood flow of 348+/-2.2 ml/min. Recirculation rates evaluated with the 'slow blood flow' method were 8.6+/-0.6 and 12.1+/-0.8% for DualKT and AVA using mean values of the solute markers urea and creatinine. Due to the possibility of a comparison veno-venous vs arterio-venous blood circulation, a corrected arterio-venous access recirculation could be derived from the difference between the two, which was around 3%. The blood flow resistance of the DualKT was slightly higher than with AVA as indicated by venous pressure differences. Kt/Vdp delivered was 1.37+/-0.02 and 1.45+/-0.02 with DualKT and AVA access respectively. The loss of dialysis efficacy using catheters was estimated at 6%. However, in all cases Kt/Vdp values remained above the recommended values (Kt/Vdp > or = 1.2). Protein nutritional state, as well as conventional clinical and biochemical markers of dialysis adequacy, remained in the optimal range. CONCLUSION: Permanent venous catheters provide adequate haemodialysis on a long-term basis. Flow performances and dialysis doses are slightly reduced (5-6%) when compared with AVA. Regular assessment of dialysis performance is strongly recommended to assure dialysis adequacy. Lengthening dialysis time may represent a simple and efficient tool to compensate for reduced flow performances with catheter use.     

Influence of haemodialysis on plasma total homocysteine concentration.

BACKGROUND: The high prevalence of hyperhomocysteinaemia in uraemic patients is of interest because of the cardiovascular risk associated with increased plasma total homocysteine (tHcy) concentration. Treatment with folic acid lowers tHcy in haemodialysis patients, however, in most patients not to normohomocysteinaemic levels. With possible tHcy-lowering modifications in mind, we studied the influence of standard haemodialysis on tHcy. METHODS: In 56 folate-loaded haemodialysis patients, tHcy and parameters of dialysis adequacy were measured. In six patients, interdialytic curves of tHcy and serum creatinine concentrations were obtained and in five patients, the amount of homocysteine (Hcy) in dialysate was determined. RESULTS: tHcy (21.8+/-14.4 micromol/l) correlated significantly with Kt/V (r=0.32, P<0.05), total Kt/V (r=0.29, P<0.05), nPCR (r=0.30, P<0.05) and serum concentrations of albumin (r=0.28, P<0.05) and cobalamines (r=-0.27, P<0.05). In a multiple linear regression analysis, only serum albumin concentrations significantly predicted tHcy (r=0.34, P < 0.05). During dialysis, tHcy decreased by 28% and remained constant for at least 8 h after treatment. The amount of Hcy recovered in dialysate was 63 micromol (12-158 micromol). There was no difference in tHcy between those who had residual renal function and those who had not. CONCLUSIONS: The direct relationship between tHcy and Kt/V seemed to be mediated by the serum albumin concentration. The shape of the interdialytic tHcy curve suggested facilitated Hcy removal for at least 8 h after dialysis possibly due to reduced levels of inhibitory activities against relevant enzyme(s). The dialysed amount of Hcy did not seem to contribute significantly to Hcy removal. Thus, modifications of standard dialytic regimens are not likely to be effective from a tHcy-lowering point of view whereas convective procedures such as haemofiltration or haemodiafiltration might be more effective.     

Favourable long-term outcome by repeated percutaneous coronary revascularization in diabetic haemodialysis patients.

BACKGROUND: Diabetic haemodialysis patients have a high prevalence of coronary events and very high mortality rates. Percutaneous coronary intervention has become a well-established and routine procedure for coronary revascularization. This study investigated the long-term outcome of multiple repeated interventions in diabetic haemodialysis patients with coronary artery disease. METHODS: A retrospective study compared 37 type II diabetic haemodialysis patients with coronary artery disease and 26 non-diabetic patients matched for age, angiographic morphology, and devices of percutaneous intervention. All patients had undergone successful percutaneous intervention prior to enrollment. Percutaneous interventions were repeated in the event of restenosis or the development of a de novo lesion. RESULTS: Diabetic and non-diabetic patients were similar in terms of the number of follow-up angiograms (2.3+/-1.6 vs 2.4+/-1.5/patient) and interventions (2.2+/-1.4 vs 2.2+/-1.5/patient), incidence of target lesion revascularization (85 vs 82%), and number of de novo lesions (15 vs 17%). The cumulative survival rates after the initial percutaneous intervention were similar in the groups (42% vs 31% at 80 months). Cardiac death occurred in 33% of diabetic patients and 42% of non-diabetic patients. Repeated intervention (regression coefficient=16.0, P<0.001) and a lower left ventricular ejection fraction (regression coefficient=-12.9, P=0.047) were determined for the important clinical factors associated with the survival duration after initial coronary intervention. CONCLUSIONS: Multiple repeated percutaneous interventions reduce the long-term mortality of diabetic and non-diabetic haemodialysis patients with coronary artery disease similarly. Multiple repeated percutaneous coronary interventions are a viable option for controlling myocardial ischaemia and improving the long-term outcome in high-risk diabetic haemodialysis patients.     

Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

Clinical performance measures: the changing status of peritoneal dialysis.

BACKGROUND: The Peritoneal Dialysis-Clinical Performance Measures Project (PD-CPM) characterizes peritoneal dialysis within the U.S. Current survey results are reported and compared to those of previous years. METHODS: Prevalence data from random national samples of adult peritoneal dialysis (PD) patients participating in the United States End-Stage Renal Disease (ESRD) program have been collected annually since 1995. RESULTS: In 1995, 79% of the respondents used continuous ambulatory peritoneal dialysis (CAPD) rather than automated peritoneal dialysis (APD). The mean hematocrit (Hct) of PD patients was 32% and only 66% of individuals had a measurement of dialysis adequacy reported. The mean weekly Kt/Vurea (wKt/V) and weekly creatinine clearance (wCCr) reported for CAPD patients in 1995 were 1.9 and 67 L/1.73 m2/week, respectively. In 2000 the median age of PD patients was 55 years and 63% were white. The leading cause of ESRD was diabetes mellitus (34%) and 54% of adult PD patients performed some form of APD rather than CAPD. Age, sex, size, hematocrit, peritoneal permeability, dialysis adequacy, residual renal function and nutritional indices did not differ between APD and CAPD patients. The mean hemoglobin (Hb) for the 2000 PD-CPM population was 11.6 +/- 1.4 g/dL (mean +/- 1 SD) and 11% of patients had an average Hb below 10 g/dL. The average serum albumin was 3.5 +/- 0.5 g/dL by the bromcresol green method and 56% of subjects had an average serum albumin equal to or above 3.5 g/dL (or 3.2 g/dL by bromcresol purple). In 2000 85% of patients had a dialysis adequacy measurement reported and the mean calculated wKt/V and wCCr were 2.3 +/- 0.6 and 72.7 +/- 24.9 liters/1.73 m2/week for CAPD patients and 2.3 +/- 0.6 and 71.6 +/- 25.1 L/1.73 m2/week for APD patients. PD subjects had a mean body weight of 76 +/- 19 kg and body mass index (BMI) of 27.5 +/- 6.4 kg/m2. The protein equivalent of nitrogen appearance (nPNA) of these patients was 0.95 +/- 0.31 g/kg/day, their normalized creatinine appearance rate (nCAR) equaled 17 +/- 6.5 mg/kg/day, resulting in a percent lean body mass (%LBM) of 64 +/- 17% of actual body weight. Serum albumin correlated in a positive fashion with BMI, nPNA, nCAR and %LBM, but not with wCCr. CONCLUSIONS: The majority of indicator variables monitored by the PD-CPM have improved since 1995. PD patients have higher hemoglobins and a greater proportion of patients meet the criteria for adequate dialysis. Serum albumin values, however, remain marginal and unchanged over the five-year project. Furthermore, serum albumin values fail to correlate with the intensity of renal replacement therapy and are not strongly correlated with alternative estimates of nutritional status.     

Effect of dialysis dose on nutritional status of children on chronic hemodialysis.

It had been suggested that larger hemodialysis (HD) doses in children could result in better appetite, higher protein intake, better nutritional status and better growth. We investigated how different HD doses affect protein intake and nutritional status of children on chronic HD. Indices of nutritional status used were normalized protein catabolic rate (nPCR) calculated by formal 3-sample urea kinetic modeling and serum albumin level. Data of 38 HD sessions in 15 stable patients (6 males, 9 females) aged 14.5 +/- 3.28 years (mean +/- SD) were analyzed. HD sessions were divided into three groups based on delivered Kt/V: group 1 (n = 5), inadequate (Kt/V < 1.3, mean 1.05 +/- 0.14); group 2 (n = 12), adequate (Kt/V = 1.3-1.6, mean 1.50 +/- 0.07) and group 3 (n = 21), high (Kt/V >1.6, mean 1.94 +/- 0.22). Mean nPCR and Kt/V per patient during the studied week were estimated for 11 patients in whom 3 HD sessions were available within the 38 sessions analyzed. Serum albumin level was adequate in all patients (43.77 +/- 2.28 g/l). Mean overall Kt/V and nPCR were 1.68 +/- 0.36 and 1.26 +/- 0.23, respectively, r = 0.430. Average nPCR differed between groups depending on Kt/V. It was lowest in group 1 (1.01 +/- 0.12 g/kg/day) where the highest correlation between nPCR and Kt/V was found (r = 0.648). nPCR was higher and similar in groups 2 (1.27 +/- 0.23 g/kg/day) and 3 (1.31 +/- 0.22 g/kg/day), with low correlation coefficients between nPCR and Kt/V in both groups (r = 0.275 and r = 0.197, respectively). A weak positive correlation (r = 0.249) between nPCR and Kt/V was found when average weekly values per patient (n = 11) were analyzed. Results of groups 1 and 2 confirm, what is already well established in adults, that adequate dialysis needs to be achieved in order to insure good protein intake. However, our data clearly show that nPCR did not increase with a further increase in delivered HD dose, i.e. Kt/V >1.6. Our results show that the nutritional status of children on chronic HD does not seem to benefit from very high HD doses (Kt/V >1.6).