Omeprazole attenuates oxygen-derived free radical production from human neutrophils

To look for patients with extreme urea rebound, we drew intradialytic samples one third of the way into dialysis during routine modeling for 3 months. The samples taken postdialysis were obtained after stopping the blood pump, without any slow flow period. Using the Smye equations, the intradialytic urea level was used to predict urea rebound, expressed as Kt/V-equilibrated minus Kt/V-single pool (deltaKt/V). Results were averaged for the 3-month period in 369 patients. Mean estimated deltaKt/V was -0.20 +/- 0.13, which was similar to but slightly higher than the predicted value (-0.6 x K/V + 0.03) of -0.19 +/- 0.04. In 27 patients, extreme rebound (mean deltaKt/V < -0.40) was found. Sixteen of these patients consented to further study, but only after access revision in four patients. In these patients, additional slow flow samples after 15 seconds and 2 minutes of slow flow, respectively, were drawn one third of the way into dialysis and postdialysis, and a sample was drawn 30 minutes after dialysis. On restudy, postdialysis rebound was still high with full flow samples deltaKt/V = -0.40 +/- 25, but was much lower (-0.18 +/- 0.07) and similar to predicted rebound (-0.19 +/- 0.05; P = NS) when based on 15-second slow flow samples. Eight of the 16 had marked (>15%) access recirculation by urea sampling, and deltaKt/V based on full flow post samples correlated with access recirculation (r = -0.91). The results suggest that the Smye method is valuable for identifying patients with aberrantly large postdialysis rebound values. When the postdialysis samples are drawn without an antecedent slow flow period, most patients with extreme rebound values turn out to have marked access recirculation.     

Use of iohexol to quantify hemodialysis delivered and residual renal function: technical note

BACKGROUND: Classically, urea (molecular wt = 60) is used to determine the urea reduction ratio (URR) or clearance, based on volume of distribution (Kt/V). These methods are subject to many errors. The purpose of this study was to determine whether iohexol (Io; molecular wt = 821) could be used instead of urea and provide better information as well as middle molecule clearance data. METHODS: Ten hemodialysis (HD) patients were evaluated. All were dialyzed for three hours, and a single bolus of 100 ml of Io was injected immediately post-HD. For direct dialysis quantification (DDQ), the spent dialysate was collected in a drum, and urea and iodine (I) determined immediately prior to, at the end of, and 30 minutes post-HD. As routinely used, DDQ measures clearance directly rather than estimates the levels. RESULTS: Calculated Kt/V urea (1.21+/-0.05) significantly overestimated DDQ Kt/V urea (0.78+/-0.04, P < 0.001) whereas calculated and DDQ Kt/V Io were similar (1.44+/-0.10 vs. 1.36+/-0.05). The URR and iohexol reduction ratio (IoRR) were also different (0.63+/-0.02 vs. 0.69+/-0.02; P < 0.002) with a urea but not Io rebound (URR30 min 0.59+/-0.02, P < 0.05). Calculated urea clearance (C(urea)), 247+/-21 ml/min, significantly overestimated DDQ C(urea) (157+/-10 ml/min P < 0.001). Calculated CIo and DDQ CIo, however, were similar (109+/-8 vs. 104+/-7 ml/min). Total body clearance (TBC) in six anuric subjects was 2.5+/-0.3 ml/min, and in four oliguric subjects was 5.2+/-0.5 ml/min. In 10 additional patients, direct urine measurements demonstrated a non-renal clearance (NRC) of 2.97+/-0.18 ml/min, which was 4.0+/-0.3% of body wt. Use of this factor allowed an estimation of residual renal function (RRF) that accurately reflected measured RRF (1.32+/-0.53 vs. 1.42+/-0.55 ml/min) CONCLUSION: A single injection of Io can be used to determine Kt/V, RR, and RRF without rebound or the inconvenience of urine collection. It may also represent middle molecule clearance better than urea kinetics, and may serve as a superior method for determining HD delivered and dialysis adequacy.     

Cesarean section rates: effects of participation in a performance measurement project

BACKGROUND: According to previous studies, postdialysis urea rebound (PDUR) is achieved within 30-90 min, leading to an overestimation of Kt/V of between 15 and 40% in 3- to 5-hour dialysis. The purpose of the study was to assess the impact of PDUR on the urea reduction ratio (URR), Kt/V and normal protein catabolic rate (nPCR) with long 8-hour slow hemodialysis. METHODS: This study was performed in 18 patients (13 males/5 females), 62.5 +/- 11.7 years of age, hemodialyzed for 3-265 months. Initial nephropathies were: 3 diabetes; 2 polycystic kidney disease; 3 interstitial nephritis; 2 nephrosclerosis; 3 chronic glomerulonephritis, and 5 undetermined. Residual renal function was negligible. The dialysis sessions were performed using 1- to 1.8-m2 cellulosic dialyzers during 8 h, 3 times a week. Blood flow was 220 ml/min, dialysate flow 500 ml/min, acetate or bicarbonate buffer was used. Serial measurements of the urea concentration were obtained before dialysis, immediately after dialysis (low flow at t = 0), and at 5, 10, 20, 30, 40, 60, 90 and 120 min, and before the next session. The low-flow method was used to evaluate the access recirculation, second-generation Daugirdas formulas for Kt/V, and Watson formulas for total body water volume estimation. The difference between the expected urea generation (UG) and urea measured after dialysis (global PDUR) defines net PDUR (n-PDUR). RESULTS: The n-PDUR usually became stable after 58 +/- 25 (30-90) min. Its mean value was 17 +/- 10% of the 30-second low-flow postdialysis urea (3.9 +/- 2 mmol/l). This small postdialysis urea value and the importance of UG in comparison with shorter dialysis justify the use of n-PDUR. Ignoring n-PDUR would lead to a significant 4% overestimation (p < 0.001) of the URR (79 +/- 7 vs. 76 +/- 8%), 12% of Kt/V (1.9 +/- 0.4 to 1.7 +/- 0.38) and 4% of the nPCR (1.1 +/- 0.3 to 1.05 +/- 0.3). n-PDUR correlated negatively with postdialysis urea (r = 0.45 p = 0.05), positively with URR (r = 0.31 p = 0.01) and Kt/V (r = 0.3 p = 0.03) but not with K, and negatively with the urea distribution volume (r = 0.33 p = 0.05). Mean total recirculation, ultrafiltration rate, predialysis urea levels and urea clearance did not correlate with n-PDUR. CONCLUSION: We found a significant PDUR in long-slow hemodialysis after a mean of 1 h after dialysis. This PDUR has a less important impact upon dialysis delivery estimation than short 3- to 5-hour hemodialysis, especially for the lower Kt/V or URR ranges. This is explained by the low-flux, high-efficiency, and long-term dialysis. Its inter-individual variability incites us to calculate PDUR on an individual basis.     

Impaired delivery of hemodialysis prescriptions: an analysis of causes and an approach to evaluation

Serial kinetic modeling is commonly used in hemodialysis to assess the adequacy of dialysis. A variety of problems lead to declining Kt/V in previously stable patients. These include noncompliance, vascular access recirculation, and dialyzer dysfunction. The purpose of this study was to find the relative frequencies of these problems in a group of patients undergoing routine hemodialysis. Simultaneous urea kinetic modeling and access recirculation were tested during 3 consecutive months. The baseline Kt/V was defined as the average of each patient's Kt/V values obtained during the previous 4 mo. A clinically important fall in Kt/V was defined as a decline of > or =0.2 if the baseline Kt/V was > or =1.2, or a decline of > or =0.1 if the baseline Kt/V was <1.2. Ninety-three of 375 (25%) sessions met the criteria for a significant decline in urea kinetic modeling. The baseline Kt/V in this group was 1.33 +/- 0.20 (mean +/- SEM) and declined to 1.02 +/- 0.18 in the abnormal month (P < 0.05). In 42% of instances with a decline of Kt/V, reduced blood processing due to a lower blood flow or shorter time than prescribed was responsible. Recirculation of >12% was found in 25% of sessions with a decrease in Kt/V. These patients most often had access dysfunction or reversed needles. The remaining one-third of patients with decreases in Kt/V had no problem identified, and subsequent monthly kinetic modeling results returned to baseline. These results suggest that analysis of falling urea kinetic modeling results should include a careful review of the dialysis record for reductions in prescribed time or blood flow rates followed by vascular access testing. If these evaluations are unrevealing, urea kinetic modeling results usually return to baseline in the next month.     

Chronic renal replacement therapy in children: which index is best for adequacy?

BACKGROUND: The dialysis dose, Kt/V, and Solute Removal Index (SRI) have been proposed as tools to measure and compare adequacy of different renal replacement therapies in adults. The aim of our study was to elucidate whether the Kt/V and SRI could be appropriate parameters to compare different treatments and define adequacy targets in children. METHODS: Twenty-two pediatric chronic dialysis patients (2 to 17 years) were prospectively studied. Six patients were on continuous ambulatory peritoneal dialysis (CAPD), 7 patients were on automatic nightly peritoneal dialysis (ANPD), and 9 were on hemodialysis (HD). Patients had no peritonitis and were not hospitalized during the previous two months and, as proved by growth and subjective well being, were in steady state condition at the initiation of the protocol. As a consequence, the treatment delivered was assumed to be adequate and the prospective analysis was carried out within one month. Urea levels in dialysate, plasma and urine were measured to determine urea kinetics and measure adequacy parameters. RESULTS: Instantaneous urea clearance was much higher when hemodialysis was used (124.67 +/- 32.04 ml/min) compared to CAPD (2.79 +/- 0.29 ml/min) and ANPD (6.60 +/- 1.42 ml/min), as expected. The Urea dialytic clearance per week was greater in HD (67320 +/- 17299 ml) than in CAPD(28144 +/- 2895 ml) and ANPD (29910 +/- 4234 ml). Residual renal function contributed to the overall weekly clearance by 47% in CAPD, while it was only by 19% in HD and 26% in ANPD. The overall weekly clearance was therefore 79,842 ml/week in HD, 53,340 ml/week in CAPD and 41,012 ml/week in ANPD. Weekly dialytic Kt/V results were much higher in HD (3.75) than in CAPD (1.78) and ANPD (2.37). To these values, the renal Kt/V was added, reaching the values of overall (dialytic + renal) weekly Kt/V of 4.53 in HD, 3.41 in CAPD and 3.41 in ANPD. Although higher Kt/V values were observed in HD, when the SRI % was considered, HD appeared to be less efficient compared with the other two techniques. Since postdialytic rebound in HD patients averaged 22.5%, we may speculate that hemodialysis in children is less efficient than continuous or daily peritoneal dialysis because of a remarkable cardipulmonary recirculation and solute sequestration. CONCLUSION: In the global evaluation, dialysis SRI% appears to be more reliable as an index of adequacy compared to Kt/V in children. At least an integration between the two indices is strongly recommended.     

Assessment of dialysis adequacy using the dialysate urea monitor: preliminary experience of the dialysate urea monitor

Numerous studies have identified a strong linkage between the delivered dialysis dose (Kt/V) and the survival of hemodialysis (HD) patients. However, the current method used to calculate Kt/V requires multiple blood samples and the process is complex and time consuming. We evaluate the performance of a recently developed on-line monitor (Biostat 1000 dialysate urea monitor, Baxter) that measures the urea concentration in the effluent dialysate and displays Kt/V and nPCR immediately after hemodialysis. To verify the performance of the urea monitor, we selected 21 hemodialysis patients, calculated their Kt/V and nPCR values from blood samples obtained during each hemodialysis, and compared the results with data obtained using the urea monitor. The Kt/V and nPCR values calculated by the urea monitor were both significantly correlated with those obtained using blood samples (R = 0.804, p < 0.001 in Kt/V and R = 0.749, p < 0.001 in nPCR). Our results suggest that the urea monitor may be used for on-line assessment of dialysis adequacy and obviates the need for blood sampling.     

Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life

BACKGROUND: More frequent dialysis has been claimed to improve clinical outcome and quality of life. METHODS: Clinical status was optimized in 13 haemodialysis patients during a run-in period of 2 months with three dialysis sessions a week. Thereafter, daily home haemodialysis (DHHD, 6 sessions per week) was initiated. The total weekly dialysis dose (Kt/V) was kept constant. RESULTS: Weekly Kt/V was 3.2+/-0.13 (M+/-SEM) before, and 3.2+/-0.15 after 6 months of DHHD (NS), time-averaged concentration of urea (TACu) was 21.2+/-1.6 mmol/l and 20.1+/-0.9 mmol/l (NS). Urea reduction was 0.56+/-0.05 before DHHD, and 0.41+/-0.06 during DHHD (P<0.0001). Serum K remained unchanged, but significantly less exchange resins were used (P<0.02). Also, the dose of phosphate-binding agents could be decreased. Values for Na, K, Cl, bicarbonate, Ca, PTH, albumin, and Hb remained unchanged. Iron deficiency developed in some patients. Twenty-four-hour blood pressure monitoring showed a decrease of systolic blood pressure (141.1+/-17.2 mmHg before, and 130.9+/-19.2 mmHg during DHHD, P<0.001). Diastolic blood pressure remained constant (82.8+/-7.2 and 76.9+/-10.1 mmHg, NS). Mean arterial pressure decreased from 102.2+/-9.5 to 94.9+/-1.4 mmHg (P<0.02). Blood pressure decreased mainly in previously hypertensive patients. Mean target weight increased 0.8 kg. The amount of antihypertensive drugs used decreased from 1.88+/-0.35 to 0.75+/-0.17 (P<0.005, n=7). Dialysis sessions were much more stable, also in patients with cardiac insufficiency. Quality of life questionnaires (Rand 36, Nottingham Health Profile, Uraemic Symptoms Profile) showed a significant improvement of physical condition and fewer uraemic symptoms. CONCLUSION: DHHD compared to conventional thrice-weekly haemodialysis with similar weekly Kt/V results in an improved haemodynamic control and quality of life, but has lesser impact on metabolic regulation.     

A shared genetic mechanism for melanotic encapsulation of CM-Sephadex beads and a malaria parasite, Plasmodium cynomolgi B, in the mosquito, Anopheles gambiae

Dialysis dose and malnutrition have a great impact on the clinical out come of chronic hemodialysis patients. The interrelationships between them, however, remain undefined. Thus, we performed a study to determine the effects of increasing the dialysis dose on serum albumin concentrations and mortality in hemodialysis patients. We examined urea kinetic modeling, biochemical nutritional indices, comorbid conditions, patient survival time, and annual mortality rate. Dialysis dose, measured by Kt/V, significantly increased from 1.3 +/- 0.3 in 1987 to 1.5 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. Serum albumin level also increased from 3.8 +/- 0.4 g/dL in 1987 to 4.0 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. In 1993, 76% of patients had Kt/V > or = 1.50 compared with 45% in 1990 and 28% in 1987, whereas 82% of patients had a serum albumin level > or 4.0 g/dL in 1993 compared with 58% in 1990 and 29% in 1987. Protein catabolic rate and hematocrit also increased from 1987 to 1993, but not serum cholesterol or triglyceride. The annual mortality rate declined from 16.1% in 1987 to 13.2% in 1990 and to 8.0% in 1993. The decrease in mortality appeared to be unrelated to differences in patient selection or comorbid conditions. Serum albumin levels, hematocrit, Kt/V, and protein catabolic rate were significantly related to patient survival after age, sex, and diabetic status had been adjusted. Furthermore, there was a positive correlation between Kt/Vs and serum albumin concentration (r = 0.216, P < 0.001). Thus it appears that increasing the dose of dialysis improves serum albumin levels and perhaps survival rate in hemodialysis patients as well.     

Administration to mouse of endotoxin from gram-negative bacteria leads to activation and apoptosis of T lymphocytes

The carbamylation reaction in vivo involves the nonenzymatic, covalent attachment of isocyanic acid, the spontaneous dissociation product of urea, to proteins. Carbamylated proteins have been proposed as markers of uremia and indicators of uremic control. However, the utility of measuring carbamylated proteins has not been investigated adequately. Therefore, this study was done to determine the relationship between the carbamylation of long-lived protein (hemoglobin) with that of short-lived proteins (plasma proteins) in hemodialyzed patients. Significantly higher carbamylated hemoglobin (CHb; 157 +/- 40 microg valine hydantoin/g Hb) and carbamylated protein (CTP; 0.117 +/- 0.011 absorbance/mg protein) concentrations were found in hemodialyzed patients (N = 13) as compared to normal individuals (N = 9, 53 +/- 20 microg valine hydantoin/g Hb and 0.08 +/- 0.01 absorbance/mg protein, respectively). A high correlation was found between CHb and CTP concentrations (r = 0.87, P < 0.0001), demonstrating a strong relationship between these two different half-lived proteins. A six-month longitudinal study of seven hemodialyzed patients showed that the between subject correlations were significant for CHb versus CTP as well as CHb versus pre-dialysis urea. Correlations were not significant for CTP versus pre-dialysis urea or Kt/V, nor CHb versus Kt/V. Carbamylated hemoglobin fluctuated the most over this time period (30.1% +/- 20.2%), pre-dialysis urea and CTP varied less (18.3% +/- 13.4% and 14.9% +/- 7.5%, respectively), and Kt/V varied the least (6.3% +/- 3.3%). Within subject correlations were not significant between any two tests. It is unclear whether the lack of correlations found is real or a function of the small sample size. However, these data do show that CHb and CTP are positively associated and reflect the degree of urea exposure in the blood, but their usefulness for patients on maintenance hemodialysis is not clear.     

On-line assessment of delivered dialysis dose

BACKGROUND: The adequacy of the delivered dialysis dose is essential to prevent patient morbidity and mortality. The determination of effective ionic dialysance (D) is easy, non-invasive and inexpensive, and its use instead of effective urea clearance (K) in kinetically determining apparent" urea distribution volume (Vt) is likely to lead to a correct Kt/V, even though the Vt value may be incorrect. The aim of this study was to test the possibility of using the measurement of D to monitor Kt/V on-line during each dialysis treatment. METHODS: Forty-four patients were dialyzed using a monitor equipped with specially designed "Diascan Module" (COT; Hospal) that measures effective D by means of a single conductivity probe. Vt was calculated according to the SPVV three BUN method urea kinetic model using D instead of K values. One month later, Kt/V was calculated as Dt/V, using actual D and T values and the predetermined Vt values updated for the current final body wt. Both the Dt/V and Kt/V determined according to the Smye and Daugirdas methods were compared with the Kt/V determined using the SPVV kinetic model (Kt/Veq) RESULTS: The Kt/V values calculated using ionic dialysance and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/- 0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17, mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). CONCLUSION: Once Vt has been determined, the evaluation of ionic dialysance in stable patients makes it possible to calculate the Kt/V accurately at each dialysis session without blood or dialysate sampling, and at no additional cost.     

Evidence for an independent role of metabolic acidosis on nutritional status in haemodialysis patients

BACKGROUND: Malnutrition in haemodialysis (HD) patients has been referred to underdialysis with low protein intake, and to acidosis. However, the separate effects of underdialysis and acidosis on nutrition have not been clearly demonstrated. To evaluate the role of the dialysis dose and of metabolic acidosis on nutrition, we measured the predialysis serum HCO3, pH, serum albumin, PCRn, Kt/V, and BMI in 81 uraemic patients on maintenance bicarbonate HD for 93+/-80 months. Patients with chronic liver diseases, malignancies, and cachexia were excluded. RESULTS: Mean age was 59+/-17 years, Kt/V was 1.29+/-0.21, PCRn 1.06+/-0.22 g/kg/day, serum albumin 4.07+/-0.28 g/dl, BMI 23+/-4 kg/m2, HCO3 21.1+/-1.9 mmol/l, pH 7.36+/-0.04. Serum albumin showed a significant direct correlation with: PCRn (P=0.001), HCO3 (P=0.001), pH (P=0.002), but no correlation with Kt/V and BMI. Serum HCO3 correlated inversely with PCRn (P=0.027). Multiple regression analysis confirmed the significant role of serum bicarbonate and age, but not of Kt/V, on serum albumin concentrations. The role of PCRn appeared to be marginal compared to serum bicarbonate in determining serum albumin levels. Dividing patients into two groups, serum albumin was 3.96+/-0.22 g/dl with HCO3 < or = 20 mmol/l and 4.18+/-0.31 g/dl in those with serum HCO3 > or = 23 mmol/l (P=0.002). PCRn in the same groups was respectively 1.14+/-0.24 g/kg/day and 1.01+/-0.23 g/kg/day (P=0.03). Most importantly, serum albumin levels did not appear to be affected by the dialysis dose, with Kt/V ranging from 0.90 to 1.88. CONCLUSIONS: In HD patients with adequate Kt/V, metabolic acidosis exerts a detrimental effect on serum albumin concentrations partially independently of the protein intake, as evaluated by PCRn. In the presence of moderate to severe metabolic acidosis, PCRn does not reflect the real dietary protein intake of the patients, probably as a result of increased catabolism of endogenous proteins. For this reason PCRn should be considered with caution as an estimate of the dietary protein intake in HD patients in the presence of metabolic acidosis.     

Fluid dynamics of gingival tissues

Determining adequacy of dialysis has remained a problem for the nephrologist despite the results of the National Cooperative Dialysis Study published more than 20 years ago. Urea Kinetics Modelling (UKM) which requires computer data entry is time-consuming for the dialysis staff but is the only method that has been rigorously studied. Furthermore, it is unclear today what value of Kt/V represents ideal dialysis; the technique is subject to a number of errors associated with estimation of dialyser clearance (K) and volume of distribution of urea (V) but it is useful for calculating protein catabolic rate (PCR). Methods that use urea reduction ratios (URR) is widely used because it is simpler but not always accurate and suffer from an inability to calculate PCR. Direct dialysis quantification (DDQ) can overcome a number of these problems but it is too cumbersome for routine use. Simpler methods to determine dialysateside kinetics have the advantage of solving a number of these problems and also facilitate the calculation of PCR to determine the patient's nutritional state. In our study we have demonstrated that by taking two dialysate samples at the beginning and at the end of dialysis (2-DSM), it is possible to determine total urea removal (TUR) which is equivalent to DDQ. By taking blood samples after dialysis and before the next dialysis, it is possible to calculate the total urea generated (TUG). The ratio of TUR/TUG will provide an index of dialysis which places emphasis on removal of solute that has accumulated in the inter-dialytic interval thus re-establishing a state of equilibrium. We refer to this index as the Mass Balance Index (MBI). The MBI is also useful in helping to identify those patients whose PCR is inadequate since the mean MBI for patients with an nPCR <0.8 was 0.93 +/- 0.03 vs 1.08 +/- 0.02 in those with a PCR >0.8. In these two groups of patients the Kt/V was not significantly different, 1.49 +/- 0.07 vs 1.53 +/- 0.06, p -0.64. We suggest that the emphasis for adequacy of dialysis should shift away from Kt/V to maintaining a state of equilibrium by removing the solutes that accumulate between dialysis and by identifying those patients with an inadequate PCR.     

Conductivity: on-line monitoring of dialysis adequacy

Cardiovascular disease and the inadequacy of delivered dialysis are the main factors determining morbidity and mortality in dialysis patients. We have already demonstrated that a conductivity kinetic model makes it possible to match interdialytic sodium loading and intradialytic sodium removal (the main factor determining cardiovascular morbidity) without the need for blood samples and, thus, in routine clinical practice. The aim of the present study was to test the possibility of using the conductivity method also to determine Kt/v without blood or dialysate sampling. In 18 steady-state patients, the urea distribution volume (V) was kinetically determined once using ionic dialysance (D) values instead of those of effective urea clearance. One month later, the Kt/V was determined by using the current D and T values and the predetermined V (Dt/V), then compared with the equilibrated Kt/V computed by means of the SPVV kinetic model (eqKt/V). The mean value of Dt/V was 1.18+/-0.15; while of eqKt/V it was 1.18+/-0.16, with a mean difference of 0.00+/-0.07. The conductivity method therefore seems to be very promising not only for monitoring the sodium balance, but also for quantifying delivered dialysis. Since its simplicity and low-cost make it suitable for use at each dialysis session, the conductivity method could therefore lead to significant progress in dialytic practice by contributing to the elimination of the two main causes of morbidity and mortality in dialysis patients.     

Hypercalcemia during pulse vitamin D3 therapy in CAPD patients treated with low calcium dialysate: the role of the decreasing serum parathyroid hormone level

Oral pulse therapy with vitamin D is effective in suppressing parathyroid hormone (PTH) secretion in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism (2'hpt). However, this treatment often leads to hypercalcemia. The goals of the study were: (1) to examine whether the incidence of hypercalcemia decreases when dialysate calcium is reduced from 1.25 to 1.0 mmol/L; (2) to determine the relative role of the factors involved in the pathogenesis of hypercalcemia; and (3) to study the efficacy of a low oral pulse dose of alfacalcidol in preventing the recurrence of 2'hpt. Fourteen continuous ambulatory peritoneal dialysis patients with 2'hpt were treated with pulse oral alfacalcidol and calcium carbonate and dialyzed with a 1.0-mmol (n = 7) or a 1.25-mmol (n = 7) dialysate calcium. The response rate (87%) and the incidence (71%) and severity of hypercalcemia were similar in both groups. In the early response stage, PTH decreased by 70% in both groups, and serum ionized calcium (iCa) increased from 1.18 +/- 0.02 to 1.27 +/- 0.04 mmol/L (P < 0.005) in the 1.0 group and from 1.19 +/- 0.02 to 1.29 +/- 0.02 mmol/L in the 1.25 group (P < 0.005). Nine of the 12 responders had a further decrease in serum PTH, which was associated with an additional increase in iCa from 1.28 +/- 0.02 to 1.47 +/- 0.04 (P < 0.005). Multivariate analysis showed that the early increase in iCa was positively correlated with alfacalcidol dosage (r = 0.69). In contrast, the late increase in iCa was mostly accounted for by the decrease in serum PTH (r = -0.93). This occurred while calcium carbonate, alfacalcidol dosage, and serum 1,25 hydroxy D3 remained unchanged compared with the early response stage. Finally, an alfacalcidol dose of 1 microg twice weekly was unable to maintain serum PTH at an adequate level in the long term. These data show that a reduction in dialysate calcium from 1.25 to 1.0 mmol does not reduce the occurrence of hypercalcemia and suggest that lowering serum PTH reduces the ability of the bone to handle a calcium load within a few weeks, thus causing hypercalcemia.     

Interdialytic weight gain and nutritional parameters in chronic hemodialysis patients

The extent of interdialytic weight gain (IDWG) in chronic hemodialysis patients is usually attributed to the level of compliance with fluid restriction. However, in view of the substantial water content of food (and caloric content of beverages), IDWG also may be a function of calorie and protein intake and may reflect the nutritional state of patients. To investigate this theory, the relationship between 2-day IDWG and body weight, normalized protein catabolic rate (nPCR), serum albumin, and delivered Kt/V urea was assessed in a prospective, randomized study of 860 chronic hemodialysis patients in 56 dialysis units. Compared with patients having < 2 kg IDWG (n = 378), patients with > 3 kg IDWG (n = 138) weighed more (dry weight, 76.8 v 61.7 kg), had higher nPCR (1.15 v 0.96 g/kg/d), and had higher serum albumin levels (3.96 vs 3.79 g/dL) (all P < 0.001) but did not have different levels of Kt/V (1.04 v 1.06). When IDWG was assessed as a function of dry weight, patients with IDWG > 4.5% of dry weight (n = 151) had higher nPCR (1.17 v 0.94 g/kg/d) but weighed less (60.1 v 70.0 kg) and had a higher Kt/V (1.14 v 1.01) than patients with IDWG < 3% of dry weight (n = 355) (all P < 0.001). Artifactual association between IDWG and nPCR attributable to an accentuated two-pool effect from differing ultrafiltration requirements was unlikely as assessed by the relationship between modeled Kt/V and prescribed Kt/V determined using an anthropometric urea volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protein intake does not depend on the dose of dialysis delivered--provided Kt/V is adequate

BACKGROUND: A link between malnutrition and the dialysis dose has been recently postulated on the basis of the direct relationship between Kt/V and nPCR and an increase in dialysis therapy has been also proposed in malnourished patients or when nPCR is less than 1 g/kg b.w., but the clinical meaning of such a relationship is unclear. DESIGN: Both dietary protein intake and nPCR were simultaneously determined in a selected population of 35 well-dialysed patients (Kt/V > 0.8) and were related to the delivered dialysis dose. RESULTS: No relationship was found between measured Kt/V (1.10 +/- 0.20) and dietary protein intake (PI, 0.98 +/- 0.20 g/kg) and similarly no relationship was evident between the dialysis dose and nPCR (0.99 +/- 0.20 g/kg). Although the mean nPCR value was similar to that of protein intake, nPCR exceeded protein intake when PI was less than 1 g/kg b.w. CONCLUSION: Our results demonstrate that if the dialysis dose is adequate, protein intake is a dialysis--independent or patient--dependent variable. They also show that at least 0.9 to 1.0 g protein per kg b.w are required to maintain nitrogen balance even in well-dialysed patients.     

Accuracy of an on-line urea monitor compared with urea kinetic model and direct dialysis quantification

To verify the accuracy of a urea monitor (UM) to assess dialysis adequacy, it was compared with a modified direct dialysis quantification method (mDDQ) and with a Casino modified urea kinetic model (mUKM) algorithm. Simplified Jindal and Daugirdas formulas, an anthropometric body water Watson formula, bioelectric impedance analysis, and the Garred model have also been considered. Concerning urea removal, UM results are close to mDDQ, as are the predialytic blood urea nitrogen values obtained by UM in the initial equilibration test. Urea distribution volume results for UM, mDDQ, and bioelectric impedance analysis are similar, whereas it appears clearly overestimated by the Watson formula. Urea monitor clearances are not significantly different from mDDQ, unlike UM Kt/V, which is slightly higher than mDDQ reference value, although with a satisfactory degree of concordance. Rebound effect must be considered by sampling after the equilibration time (et) when mUKM or simplified Kt/V formulas are used: mUKMet Kt/V results are quite similar to mDDQ, as is the Daugirdas value. Regarding NPCR, UM results are neither significantly different from mDDQ nor from the Garred model, whereas mUKM results are significantly overestimated. When rebound is considered, NPCR by mUKMet and NCPR by mDDQ are identical. The UM approach is simple and practical, with a satisfactory degree of reliability for clinical practice.     

The hemodialysis prescription and cost effectiveness. Renal Physicians Association Working Committee on Clinical Guidelines

Case-mix adjusted mortality rates for patients undergoing hemodialysis for ESRD increased during the 1980s, despite the introduction of advanced dialysis technologies. Variations in dialysis practices suggest that excess mortality may be caused by inadequate uremic-toxin clearances. Cost-effectiveness analysis was used to assess whether attempts to improve uremic-toxin clearance are cost effective, assuming that these therapies are clinically effective. The medical literature was surveyed by the use of MEDLINE to assess the likelihood of clinical outcomes on the basis of the type of treatment given to the patient. Options considered in the model were delivered fractional urea clearance (Kt/V), dialysis-treatment duration, type of dialyzer membrane, dialysate, and ultrafiltration. Clinical outcomes included in the model were survival, severity of uremic symptoms, hospital days per year, and intradialytic hypotension and symptoms. Lifetime costs were calculated from data collected from a northern California dialysis center and abstracted from the literature. In the base-case scenario, it was assumed that increasing Kt/V to levels greater than 1 was effective in reducing morbidity and mortality. Under these assumptions, outpatient cost increased significantly, but the cost effectiveness of Kt/V equal to 1.5 was less than $50,000 per quality-adjusted life-year saved. These calculations indicate that, if higher levels of Kt/V prove clinically effective, they are also cost effective.     

Toward targets for initiation of chronic dialysis

OBJECTIVES: To better define the targets for initiation of chronic dialysis, we compared the relationship between the normalized protein equivalent of nitrogen appearance (nPNA, g/kg standard weight/day) and weekly urea clearance (Kt) normalized to total body water (V) in predialysis chronic renal failure (CRF) patients and in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). We also studied the relationships of other nutritional parameters to weekly Kt/Vurea in CRF patients. DESIGN: This cross-sectional study was a prospective observational design meant to study each patient once. SETTING: The University Hospital and Clinics and Harry S. Truman VA Medical Center, Columbia, Missouri. PATIENTS: Forty-five consecutive predialysis CRF patients were enrolled and the results compared with patients on CAPD and HD. RESULTS: In CRF, the nPNA calculated from urea appearance correlated with the weekly Kt/Vurea (r = 0.57, p < 0.0001) and, using exponential best-fit, nPNA = 1.217 x (1-e-0.769Kt/V). This exponential relationship was similar to that for CAPD and both were different from that in patients on HD. Likewise, nPNAs, calculated from Kjeldahl nitrogen output, and weekly Kt/Vurea were correlated (r = 0.37, p = 0.014) and, using exponential best-fit, nPNA = 1.102(1-e-0.867Kt/V), similar to the relationship in patients on CAPD. Evidence is presented that these relationships are not explained only by mathematical coupling. There was a significant correlation between the weekly Kt/Vurea and 24-hour urinary creatinine excretion. CONCLUSIONS: The findings suggest that in CRF, as in CAPD, a weekly Kt/Vurea less than 2.0 is likely to be associated with a nPNA less than 0.9 g/kg standard weight. In CRF patients, initiation of chronic dialysis should be considered if weekly renal Kt/Vurea falls below 2.0 and a nPNA greater than 0.8 is desired.