Skin-autofluorescence, a measure of tissue advanced glycation end-products (AGEs), is related to diastolic function in dialysis patients.

BACKGROUND: Diastolic dysfunction is a frequent cause of heart failure, particularly in dialysis patients. Advanced glycation end-products (AGEs) are increased in dialysis patients and are suggested to play a role in the development of diastolic dysfunction. The aim of our study was to assess whether AGE accumulation in dialysis patients is related to the presence of diastolic dysfunction. METHODS AND RESULTS: Data were analyzed from 43 dialysis patients, age 58 +/- 15 years, of whom 65% were male. Diastolic function was assessed using tissue velocity imaging (TVI) on echocardiography. Tissue AGE accumulation was measured using a validated skin-autofluorescence (skin-AF) reader. Plasma N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) were measured by stable-isotope-dilution tandem mass spectrometry. Plasma pentosidine was measured by high-performance liquid chromatography. Skin-AF correlated with mean E' (r = -0.51, P < .001), E/A ratio (r = -0.39, P = .014), and E/E' (r = 0.38, P = .019). Plasma AGEs were not significantly associated with diastolic function. Multivariable linear regression analysis revealed that 54% of the variance of average E' was explained by age (P = .007), dialysis type (P = 0.016), and skin-AF (P = .013). CONCLUSIONS: Tissue AGEs measured as skin-AF, but not plasma AGE levels, were related to diastolic function in dialysis patients. Although this may support the concept that tissue AGEs explain part of the increased prevalence of diastolic dysfunction in these patients, the ambiguous relation between plasma and tissue AGEs needs further exploring.

Differences between physicians in the likelihood of referral and acceptance of elderly patients for dialysis influence of age and comorbidity.

Background. Incidence of dialysis in elderly patients in the Netherlands is low compared to other countries. This study aims to assess the impact of patients' age and comorbidity on the likelihood of referral and acceptance of patients for dialysis and whether this is affected by physician characteristics. Methods. A vignette study was performed on 209 primary care physicians, 162 non-nephrology specialists and 20 nephrologists working in northern Netherlands. Physicians were offered six vignettes concerning case reports of patients with end-stage renal disease (ESRD) and varying comorbidities or circumstances and asked about the likelihood of referral/acceptance of the patient in the given circumstances. Results. The likelihood of referral within groups of physicians varied widely, especially within the group of primary care physicians and non-nephrology specialists, but was not affected by characteristics of the physicians. The likelihood of referral or acceptance of patients for dialysis depended on the patient's age, and type and severity of comorbidity. In general, primary care physicians and non-nephrology specialists were less likely to refer than nephrologists were willing to accept. Differences within and between groups of physicians to accept or refer were larger for 80-year-old patients than for 65-year-old patients. The differences were wider concerning patients with less severe shortness of breath and cognitive impairments and more severe diabetes and social impairments. Hardly any differences were found for patients with cancer. Conclusion. Patients' age and comorbidities affect the likelihood of referral. Differences between groups of physicians suggest that there is insufficient agreement on the extent to which these factors should affect the referral/acceptance of patients for dialysis. These findings underline the need for more research into circumstances under which patients might benefit from dialysis. Guidelines should be developed to improve the referral of elderly and less healthy patients.

Relative blood volume measurements during hemodialysis: comparisons between three noninvasive devices.

The monitoring of relative blood volume changes (DeltaRBV) has been advocated for the prevention of hemodialysis (HD) hypotension. Stand-alone devices (Crit-Line) or devices incorporated into the HD apparatus (blood volume monitor [BVM], Hemoscan) are widely used for this purpose. Comparisons between devices are scarce. The aim of this study was, first, to compare DeltaRBV results from these 3 devices with DeltaRBV calculated from changes in laboratory-derived hemoglobin (DeltaRBV-lab-Hb) and, second, to compare DeltaRBV results between the different devices. Fourteen patients received 2 HD treatments in a randomized order: one with the Hemoscan and Crit-Line combination and one with the BVM and Crit-Line combination. DeltaRBV-lab-Hb was measured at 2 and 4 hr into the HD session. Bland-Altman analyses showed that DeltaRBV results from the 3 devices differed systematically from DeltaRBV-lab-Hb, i.e., the difference between the 3 devices and DeltaRBV-lab-Hb varied significantly (p<0.05) with the magnitude of the measurement. The interdevice comparison showed considerable differences in DeltaRBV results. At the end of the treatment, a significant difference (p<0.05) between DeltaRBV measured by the Hemoscan and Crit-Line device (-9.8+/-2.7% and -11.5+/-4%, respectively) was found. In most patients, a systematic difference between Crit-Line and Hemoscan and between Crit-Line and BVM was observed. Relative blood volume change measurements by Crit-Line, Hemoscan, and BVM yield results that differ systematically from the results obtained from laboratory-derived Hb changes. Furthermore, there are substantial differences in DeltaRBV results between the 3 DeltaRBV devices.

Influence of ultrafiltration volume on blood volume changes during hemodialysis as observed in day-of-the-week analysis of hemodialysis sessions.

Monitoring of relative blood volume changes (DeltaRBV) has been propagated for the prevention of hemodialysis hypotension. Although the influence of ultrafiltration volume on DeltaRBV is well-known, there is no mention in the literature that DeltaRBV results should be interpreted differently for the first, second, or third hemodialysis session of the week. To elucidate whether DeltaRBV and its derivative, DeltaRBV normalized for ultrafiltration volume (DeltaRBV/ultrafiltration ratio), vary systematically over the week, we separately analyzed these parameters for the first, second, and third hemodialysis session of the week in 13 chronic hemodialysis patients over a 17-week period. As expected, mean (+/-SD) ultrafiltration volume was significantly (p < 0.001) higher during the first session than during the second and third hemodialysis sessions (3163 +/- 615, 2622 +/- 674 and 2607 +/- 638 ml, respectively). DeltaRBV was significantly (p < 0.01) more negative at the first session than at the second and third hemodialysis sessions (-10.1 +/- 2.7, -9.3 +/- 3.0 and -9.3 +/- 3.1%, respectively). The DeltaRBV/ultrafiltration ratio was significantly (p < 0.01) less negative at the first session than at the second and third hemodialysis sessions (-3.2 +/- 0.6, -3.5 +/- 0.8 and -3.6 +/- 0.6%/l, respectively). In conclusion, DeltaRBV and the DeltaRBV/ultrafiltration ratio differ systematically between the first and other hemodialysis sessions in patients on a thrice-weekly hemodialysis schedule, most likely as a result of different ultrafiltration volumes.

Relative blood volume changes underestimate total blood volume changes during hemodialysis.

BACKGROUND: Measurements of relative blood volume changes (DeltaRBV) during hemodialysis (HD) are based on hemoconcentration and assume uniform mixing of erythrocytes and plasma throughout the circulation. However, whole-body hematocrit (Ht) is lower than systemic Ht. During HD, a change in the ratio between whole-body to systemic Ht (F cell ratio) is likely to occur as a result of a net shift of low Ht blood from the microcirculation to the macrocirculation. Hence, DeltaRBV may differ significantly from total blood volume changes (DeltaTBV). Therefore, this study compared DeltaRBV and DeltaTBV during HD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Plasma and erythrocyte volumes were measured using (125)I- and (123)I-radioiodinated albumin and (51)Cr-labeled erythrocytes, respectively. After validation of the standardized method in two patients on a nondialysis day, seven patients completed the protocol during HD. (125)I-albumin and (51)Cr-labeled erythrocytes were administered 20 min before the start of HD. (123)I-albumin was administered at 160 min into the HD session to quantify and correct for (125)I-albumin leakage. DeltaRBV was measured continuously throughout HD. The F cell ratio was derived from whole-body and systemic Ht. RESULTS: Total ultrafiltration volume was 2450 +/- 770 ml. TBV declined from 5905 +/- 824 to 4877 +/- 722 ml during HD. Thus, TBV declined 17.3 +/- 4.4%, whereas the RBV decline was only 8.2 +/- 3.7% (P = 0.001). The F cell ratio increased from 0.896 +/- 0.036 to 0.993 +/- 0.049 during HD (P = 0.002). CONCLUSIONS: DeltaRBV significantly underestimates DeltaTBV during HD. The rise in F cell ratio strongly suggests that during HD, blood translocates from the microcirculation to the macrocirculation, probably as a cardiovascular compensatory mechanism in response to hypovolemia.

Differences between physicians in the likelihood of referral and acceptance of elderly patients for dialysis-influence of age and comorbidity.

BACKGROUND: Incidence of dialysis in elderly patients in the Netherlands is low compared to other countries. This study aims to assess the impact of patients' age and comorbidity on the likelihood of referral and acceptance of patients for dialysis and whether this is affected by physician characteristics. METHODS: A vignette study was performed among 209 primary care physicians, 162 non-nephrology specialists and 20 nephrologists working in the north of the Netherlands. Physicians were offered six vignettes concerning case-reports of patients with end-stage renal disease (ESRD) and varying comorbidities or circumstances and asked about the likelihood of referral/acceptance of the patient in the given circumstances. RESULTS: The likelihood of referral within groups of physicians varied widely, especially within the group of primary care physicians and non-nephrology specialists, but was not affected by characteristics of physicians. The likelihood of referral or acceptance of patients for dialysis depended on the patient's age, and type and severity of comorbidity. In general, primary care physicians and non-nephrology specialists were less likely to refer than nephrologists were to accept. Differences within and between groups of physicians were larger for 80- than for 65-year-old patients, and for patients with less severe shortness of breath and cognitive impairments and more severe diabetes and social impairments. Hardly any differences were found for patients with cancer. CONCLUSION: Patients' age and comorbidities affect the likelihood of referral. Differences between groups of physicians suggest that there is insufficient agreement on the extent to which these factors should affect the referral/acceptance of patients for dialysis. These findings underline the need for more research into circumstances under which patients might benefit from dialysis. Guidelines should be developed to improve the referral of elderly and less healthy patients.

High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients.

BACKGROUND: Hyperphosphataemia is associated with increased mortality in patients with chronic kidney disease (CKD) stage IV or on dialysis. Furthermore, in animal studies, elevated plasma phosphate has been shown to be associated with an accelerated decline in renal function. The aim of this study was to determine the association of plasma phosphate with renal function loss and mortality in CKD stage IV-V pre-dialysis patients with GFR <20 ml/min/1.73 m(2). METHODS: Incident pre-dialysis patients were included between 1999 and 2001 in the multi-centre PREPARE study, and followed until 2003 or death. Rate of decline in renal function for each patient was calculated by linear regression using the Modification of Diet in Renal Disease (MDRD) formula to estimate GFR (eGFR). RESULTS: A total of 448 patients were included [mean (SD) age 60 (15) years, eGFR 13 (5.4) ml/min/1.73 m(2), decline in renal function 0.38 (0.95) ml/min/month]. Phosphate concentration at baseline was 4.71 (1.16) mg/dl, calcium 9.25 (0.77) mg/dl and calcium-phosphate product 43.5 (10.9) mg(2)/dl(2). For each mg/dl higher phosphate concentration, the mean (95% CI) decline in renal function increased with 0.154 (0.071-0.237) ml/min/month. After adjustment, this association remained [beta 0.178 (0.082-0.275)]. Seven percent of the patients died. Crude mortality risk was 1.25 (0.85-1.84) per mg/dl increase in phosphate, which increased to 1.62 (1.02-2.59) after adjustment. CONCLUSIONS: High plasma phosphate is an independent risk factor for a more rapid decline in renal function and a higher mortality during the pre-dialysis phase. Plasma phosphate within the normal range is likely of vital importance in pre-dialysis patients.

Effects of relative blood volume-controlled hemodialysis on blood pressure and volume status in hypertensive patients.

In hypertensive hemodialysis (HD) patients, dry weight reduction to normalize blood pressure (BP) often results in increased frequency of HD hypotension. Because HD with blood volume tracking (BVT) has been shown to improve intra-HD hemodynamic stability, we performed a prospective, randomized study to test whether BVT is more effective than standard hemodialysis (SHD) in the management of hypertension by dry weight reduction. After a run-in period of 4 weeks on SHD, 28 patients were randomly assigned for a 12-week treatment period with either SHD (n = 14) or BVT (n = 14). The mean pre-HD and post-HD weight did not change over time in either group. In the BVT group, pre-HD systolic and diastolic BP decreased on average 22.5 mm Hg and 8.3 mm Hg, respectively (both p < 0.05), whereas BP did not change in the SHD group. Extracellular water and cardiothoracic ratio decreased significantly (all p < 0.05) in the BVT group but not in the SHD group. Brain natriuretic peptide levels declined only in the BVT group, without reaching statistical significance. The frequency of HD hypotensive episodes decreased significantly (p < 0.05) in the BVT group and was unchanged in the SHD group. HD with BVT was associated with a significant reduction in pre-HD BP. At the same time, the frequency of intra-HD hypotensive episodes decreased. Although the mean weight did not change, the reductions in cardiothoracic ratio and extracellular water suggest that HD with BVT resulted in optimization of volume status.

Effect of high and low ultrafiltration volume during hemodialysis on relative blood volume.

Achieving an optimal post-hemodialysis hydration status may be difficult because objective criteria for dry weight are lacking. Both relative blood volume changes (DeltaRBV) at the end of hemodialysis and DeltaRBV normalized for ultrafiltration volume (DeltaRBV/UF ratio) have been reported to indicate post-hemodialysis volume status. A parameter for volume status should not be influenced by variations in ultrafiltration volume. However, if the volume that has to be ultrafiltrated to reach dry weight varies as a result of variations in pre-hemodialysis weight, either DeltaRBV or the DeltaRBV/UF ratio (or both) must change. To elucidate the relation between intradialytic ultrafiltration volume versus DeltaRBV and its derivative, the DeltaRBV/UF ratio, we studied the effect of a relatively high (mean+/- SD, 2.7+/- 0.5 l) and low (1.5+/- 0.3 l) intradialytic ultrafiltration volume on these parameters in eight patients. Post-hemodialysis weight was comparable in low and high ultrafiltration volume sessions. The average end-hemodialysis DeltaRBV did not differ between high (-6.7+/- 2.5%) and low ultrafiltration volume sessions (-7.3+/- 1.0%; NS), but the intraindividual variation was considerable. The DeltaRBV/UF ratio differed markedly (p<0.001) between high (-2.4+/- 0.8 %/l) and low (-4.9+/- 1.3 %/l) ultrafiltration volume sessions. In conclusion, the considerable random intraindividual variation of DeltaRBV and the systematic change of the DeltaRBV/UF ratio with variations in intradialytic ultrafiltration volume limit the use of these parameters as an aid to assess hydration status in hemodialysis patients.

Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis.

Automatic feedback systems have been designed to control relative blood volume changes during hemodialysis (HD) as hypovolemia plays a major role in the development of dialysis hypotension. Of these systems, one is based on the concept of blood volume tracking (BVT). BVT has been shown to improve intra-HD hemodynamic stability. We first questioned whether BVT also improves post-HD blood pressure stability in hypotension-prone patients and second, whether BVT is effective in reducing the post-HD weight as many hypotension-prone patients are overhydrated because of an inability to reach dry weight. After a 3-week period on standard HD, 12 hypotension-prone patients were treated with two consecutive BVT treatment protocols. During the first BVT period of 3 weeks, the post-HD target weight was kept identical compared with the standard HD period (BVT-constant weight; BVT-cw). During the second BVT period of 6 weeks, we gradually tried to lower the post-HD target weight (BVT-reduced weight; BVT-rw). In the last week of each period, we studied intra-HD and 24 hr post-HD blood pressure behavior by ambulatory blood pressure measurement (ABPM). Pre- and post-HD weight did not differ between standard HD and either BVT-cw or BVT-rw. Heart size on a standing pre-dialysis chest X-ray did not change significantly throughout the study. There were less episodes of dialysis hypotension during BVT compared with standard HD (both BVT periods: p<0.01). ABPM data were complete in 10 patients. During the first 16 hr post-HD, systolic blood pressure was significantly higher with BVT in comparison with standard HD (both BVT periods: p<0.05). The use of BVT in hypotension-prone patients is associated with higher systolic blood pressures for as long as 16 hr post-HD. BVT was not effective in reducing the post-HD target weight in this patient group.

Within-session and between-session variability of haemodialysis shunt flow measurements.

BACKGROUND: Knowledge of the variability of a measurement method is essential for its clinical application. We investigated the variability of shunt flow measurements, since this is a relatively neglected area in the literature. In particular, no direct comparison of between-session and within-session variability was available until now. METHODS: During two consecutive dialysis sessions, shunt flow was measured three times with the ultrasound dilution method in 24 chronic haemodialysis patients with various types of shunts. Needle orientation and blood pressure at the time of flow measurement were recorded. In these patients, shunt flow was also measured three times by duplex ultrasound before the first dialysis session. RESULTS: The within-session variation coefficient (VC) of shunt flow measured with ultrasound dilution was 7.7%, whereas the between-session VC was 14.2% (n.s.). The within-session VC of Doppler shunt flow was 11.6% which was not significantly different from the corresponding figure of ultrasound dilution. Analysis of subgroups showed that changes in needle orientation caused large differences between sessions in radiocephalic fistulas but not in brachiocephalic fistulas: in the radiocephalic fistulas with the same needle orientation, VC was 6.7%, but with different needle orientation it was 23.5% (P = 0.02); the corresponding figures for brachiocephalic fistulas were 14.6% (same direction) and 11.4% (different direction, n.s.). CONCLUSION: Reproducibility of shunt flow measurements between dialysis sessions in radiocephalic fistulas is critically dependent on similar needle orientation. With similar needle position and correction for blood pressure differences, flow changes of more than 20-25% are likely to reflect true flow changes. The variability of duplex flow measurements is at least as large as that of the ultrasound dilution method.

Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease.

Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dialysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients compared with normal control subjects (2.8 vs. 2.0 arbitrary units [a.u.], P < .0001). Although fluorescence levels were significantly decreased in transplant recipients compared with dialysis patients (2.5 vs. 2.8 a.u., P < .0001), fluorescence in transplant recipients was higher than in controls (2.5 vs. 2.0 a.u., P < .0001). In transplant recipients, fluorescence correlated positively with the duration of dialysis prior to transplantation (R = 0.21, P < .0001), and negatively with creatinine clearance (R = -0.34, P < .0001). No correlation was found between time after transplantation and fluorescence in transplant recipients (R = -0.10, P = .10). Fluorescence in dialysis patients was positively correlated with duration of dialysis (R = 0.36, P = .042). Our results, like those of others, suggest that kidney transplantation does not fully correct increased AGE levels found in dialysis patients. The increased AGE levels in kidney transplant recipients cannot be explained by the differences in renal function alone. The availability of a simple, noninvasive method (AGE-Reader) to measure AGE accumulation may be used to monitor AGE accumulation in a clinical setting as well as in a study setting.

Oxidative metabolism appears to be reduced in long-term hemodialysis patients.

BACKGROUND: As part of a study of whole-body protein metabolism in hemodialysis (HD) patients, we obtained values for whole-body bicarbonate production in control subjects and HD patients before and during dialysis by using stable isotopically labeled bicarbonate. Indirect calorimetry measurements have shown normal or increased energy expenditure in HD patients, which has been used to explain the malnutrition in many of these patients. However, this method becomes inaccurate when the dynamics of whole-body bicarbonate production change during measurement, as is the case with HD patients during dialysis. METHODS: Whole-body bicarbonate production was measured in 6 control subjects, 9 patients on a nondialysis day (HD-), and 8 patients during an HD session (HD+) by means of a primed constant infusion of carbon 13 (13C)-labeled sodium carbonate (NaH13CO3). 13C-abundance of expired carbon dioxide was measured by means of isotope ratio mass spectrometry. RESULTS: Carbon dioxide production was 141 +/- 12, 123 +/- 11*, and 148 +/- 19 micromol/kg/min for the control, HD-, and HD+ groups, respectively (*P < 0.05 compared with the control and HD+ groups). Values for energy expenditure were derived and were 29.1 +/- 2.4, 24.9 +/- 2.1*, and 32.6 +/- 2.0 kcal/kg/day, respectively (*P < 0.05 compared with the control and HD+ groups). CONCLUSION: Whole-body oxidation in HD patients is reduced compared with control subjects. During dialysis, bicarbonate turnover, as well as carbon dioxide expiration, increases because of the influx of bicarbonate from the dialyzer.

Membrane biocompatibility does not affect whole body protein metabolism during dialysis.

BACKGROUND: Protein-calorie malnutrition is present in 30-50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to incompatibility of the dialyzer during the dialysis session. METHODS: Five patients were dialyzed during 2 periods of 3 weeks (cross-over) with either a single-use low-flux polysulfone or cellulose triacetate (biocompatible) or a single-use cuprophan (bio-incompatible) membrane. As a measure of whole body protein metabolism, a primed constant infusion of L-[1-(13)C]-valine was used during a 4-hour dialysis session. RESULTS: Cuprophan was a more powerful activator of the complement system than other membranes. Protein metabolism parameters during both study protocols were not different and resulted in the same protein balance during polysulfone/cellulose triacetate (-15 +/- 3) and cuprophan (-13 +/- 2 micromol/kg/h) dialysis. CONCLUSION: In stable hemodialysis patients with no apparent complications, protein metabolism during dialysis is not affected by the compatibility of the dialysis membrane.

The effects of a low-to-moderate intensity pre-conditioning exercise programme linked with exercise counselling for sedentary haemodialysis patients in The Netherlands: results of a randomized clinical trial.

OBJECTIVES: The purpose of this study is to determine whether a low-to-moderate intensity pre-conditioning exercise programme linked with exercise counselling could improve behavioural change, physical fitness, physiological condition and health-related quality of life of sedentary haemodialysis patients in The Netherlands. METHODS: Ninety-six haemodialysis patients of the Groningen Dialysis Center were randomized into an exercise group (n = 53) and a control group (n = 43). The exercise programme consists of cycling during dialysis together with a pre-dialysis strength training programme lasting 12 weeks. The intensity of the exercise programme is condition level 12-16 according to the rate of perceived exertion (RPE). Motivational interviewing techniques were used for exercise counselling. Before and after the intervention, both groups were tested on behavioural change and physical fitness components such as reaction time, manual dexterity, lower extremity muscle strength and VO2 peak. Physiological conditions such as weight, blood pressure, haemoglobin and haematocrit values, cholesterol and Kt/V were obtained from the medical records. Health-related quality of life assessment included RAND-36 scores, symptoms and depression. RESULTS: A group x time analysis with MANOVA (repeated measures) demonstrates that participation in a low-to-moderate intensity exercise programme linked with exercise counselling yields a significant increase in behavioural change, reaction time, lower extremity muscle strength, Kt/V and three components of quality of life, and no significant effects in the control group. CONCLUSION: Participating in a low-to-moderate intensity pre-conditioning exercise programme showed beneficial effects on behavioural change, physical fitness, physiological conditions and health-related quality of life.

Comparison of amino acid oxidation and urea metabolism in haemodialysis patients during fasting and meal intake.

BACKGROUND: The PNA (protein equivalent of nitrogen appearance) is used to calculate protein intake from urea kinetics. One of the essential assumptions in the calculation of PNA is that urea accumulation in haemodialysis (HD) patients is equivalent to amino acid oxidation. However, urea is hydrolysed in the intestine and the resulting ammonia could be used metabolically. The magnitude and dependence on protein intake of this process are unknown in HD patients. METHODS: Seven HD patients were studied twice, 1 week apart, on a similar protocol. After an overnight fast, patients fasted in the morning and received meals in the afternoon. On one day, amino acid oxidation was measured by infusion of L-[1-(13)C]valine. Urea production, measured from the dilution of [(13)C]urea, and urea accumulation, calculated from the increase in plasma urea concentration multiplied by the urea dilution volume, were measured during the other day. PNA was calculated using standard equations. RESULTS: Amino acid oxidation and urea production were not significantly different during fasting. Urea accumulation during fasting was significantly lower than both amino acid oxidation and urea production. Urea accumulation during feeding remained significantly lower than amino acid oxidation. PNA was equal to the average of the urea accumulation values during fasting and feeding. CONCLUSION: We conclude that during fasting, urea accumulation is not associated with amino acid oxidation or urea production. During meal intake, amino acid oxidation, urea production and urea accumulation show acutely an almost identical increase. PNA represents the average of fasting and fed urea accumulation and is lower than average amino acid oxidation or urea production.

Early identification of risk factors for refractory secondary hyperparathyroidism in patients with long-term renal replacement therapy.

BACKGROUND: Secondary hyperparathyroidism can complicate renal replacement therapy (RRT) in patients with end-stage renal disease. Current medical therapies often result in hypercalcaemia and fail to correct hyperparathyroidism, but might be more effective at an early stage of disease. The aim of this study was to identify prognostic factors at the start and during the first year of RRT for refractory secondary hyperparathyroidism needing parathyroidectomy (PTx) during long-term follow-up. METHODS: A total of 202 consecutive patients starting RRT between August 1988 and August 1996 at our centre with at least 1 year of follow-up were included. Biochemical and treatment data at the start and during the first year of RRT were collected. Univariate and multivariate analyses were used to identify risk factors for PTx during follow-up. RESULTS: Thirty-three patients (16%) needed PTx after 52+/-23 months of RRT. Need for PTx was not different between patients undergoing haemodialysis and peritoneal dialysis, but was associated with parameters reflecting calcium and phosphate control at start and after 1 year of RRT. In a Cox multivariate model, serum parathyroid hormone [relative risk (RR): 1.02 per pmol/l; P<0.001], phosphate (RR: 1.107 per 0.1 mmol/l; P = 0.002) and alkaline phosphatase (RR: 1.004 per U/l; P = 0.049) after 1 year of RRT were independently associated with increased risk for PTx. CONCLUSIONS: Failure of control of calcium-phosphate metabolism at the start of and early during RRT is strongly associated with PTx during long-term follow-up. Given the high prevalence of insufficient phosphate control, patients may benefit from aggressive correction of serum phosphate in the pre-dialysis and early dialysis period.

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.