How to improve dialysis adequacy in patients with vascular access problems.

Blood flow rate is a critical factor in the achievement of an adequate dialysis dose. The aim of this review is to evaluate the possibility of optimizing dialysis dose in terms of Kt/V in patients with reduced vascular access (VA) flow rate, considering effective blood flow (Qb eff), recirculation, access flow and hemodialyzer. In patients where the achievement of adequate blood flow rates are difficult to obtain and no surgical revision is necessary, to avoid under dialysis the increase in the treatment time should be the first choice solution. If such a solution is difficult for various reasons, a forced partial blood flow recirculation, especially in central venous catheters (CVCs) with reversed lines can be useful, on condition that the dialysis session is prolonged. The possibility of increasing the efficiency of dialysis through an increase in filter clearance has to be considered. Monitoring arterial pre-pump pressure (P asp) and optimizing ratio P asp/Qb eff during hemodialysis (HD) is one possible solution to improve blood flow rates, but it is necessary to educate and involve the staff. Recent developments in a new class of highly effective hemodialyzer due to dialysate distribution, has opened up interesting opportunities in terms of dialysis adequacy in patients with reduced VA flow rate.

Evaluation of hygiene and safety controls for on-line paired hemodiafiltration (PHF).

BACKGROUND: On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical benefits however it also requires strict attention to hygiene and safety as notable quantities of liquid are reinfused into the patient. Although most centers are improving their attention to water quality, a frequent concern is the inadvertent or accidental contamination of water and whether the redundant safety controls are sufficient to protect the patient. In the present study, in order to simulate a worst-case safety condition, we tested in vitro the reliability of paired hemodiafiltration - (PHF), under low, moderate and high bacterial contamination of the water supply. Tests were performed using various bacterial concentrations (range 85-2000 cfu/mL) of Pseudomonas Aeruginosa. Samples were analyzed from different sites throughout the entire on-line hemodiafiltration circuit for bacteria endotoxin, fungus and ability to stimulate whole blood production of TNFalfa. RESULTS: In the in vitro contamination study, with the three bacterial concentrations tested at various points of the circuit, bacteria were below the level of detection and endotoxins were < 0.01 UE/mL. Addition of dialysate samples taken after the first stage of microfiltration, as well as after the first and second stage of ultrafiltration and incubated with whole blood were not associated with stimulated production of TNFalfa . CONCLUSIONS: PHF appeared to be a safe and feasible method for on-line hemodiafiltration even in the unforeseen presence of bacterial contamination of the feed water or water distribution system.

Leptin and beta2-microglobulin kinetics with three different dialysis modalities.

BACKGROUND: Leptin is a protein produced by fat cells and involved in body weight regulation. In patients with normal kidney function, leptin has been considered an independent predictor of cardiovascular events. In uremic patients, leptin in plasma serum was assumed to be associated with malnutrition, inflammation and atherosclerosis. Because of its molecular weight and characteristics, leptin can be considered as a protein-bound uremic retention solute. Some authors have reported the possibility of decreasing the serum leptin concentration with high flux membranes, but limited data are available on the elimination with medium-flux membranes or alternative dialysis strategies such as hemodiafiltration. METHODS: We evaluated the kinetics of leptin and beta2m in a study of 18 chronic hemodialysis patients using low-flux, medium-flux and high-flux biocompatible membranes, the last one used in hemodiafiltration (HDF). Blood samples for leptin and beta2m were collected pre- and post-treatment and 30 minutes after the end of treatment, over a 1-week period that included 3 dialysis sessions. Clearances of leptin and beta2m across the dialyzer were also determined directly from the arterial and venous blood concentrations 60 and 210 minutes after starting dialysis. RESULTS: At baseline, all groups showed similar leptin (18.8+/-4.4 ng/mL) and beta2m concentrations (29.2+/-7.1 ng/mL). After a single dialysis session, a reduction of both solutes was observed with HDF (39.8+/-1.9%, 78.1+/-4.9) and medium flux membranes (18.2+/-0.9%, 52.2+/-1.7%), whereas the concentrations remained unchanged with the low-flux membranes. After one-week period, a trend of reduction of plasma pre dialysis leptin and beta2m were observed with HDF and medium flux membranes. At 60 minutes, HDF showed the best instantaneous clearance across the filter for leptin (56.2+/-10.1 ml/min) and beta2m (75.3+/-4.4 ml/min). The magnitude of post dialysis rebound of leptin at 30 min was variable and strongly correlated with the instantaneous clearance of the solute (r2= 0.88). CONCLUSIONS: Leptin serum concentration can be influenced by dialysis modalities and membrane permeability; data on rebound suggest a multicompartimental kinetic of leptin similar to beta2m. Leptin removal, as measured by the reduction rate, can be considered as an index of dialysis efficiency for protein-bound uremic retention solutes.

[Safety controls in a new hemodiafiltration on line technique (PHF)]. / Controlli di sicurezza in una nuova tecnica di emodiafiltrazione on-line (PHF).

PURPOSE: On-line hemodiafiltration (HDF) is gaining popularity due to increasing evidence of clinical benefits. The purpose of this study was to test a new on-line technique paired hemodiafiltration (PHF). In addition, we evaluated the PHF system during in vitro contamination. METHODS: Five patients used the PHF technique over a 6-month period. We performed a disinfection protocol and tested for bacteria, endotoxin, halogenated carbons and metals in the feed water, and we tested for bacteria, endotoxins and fungi in the dialysate after different ultrafiltration stages. In vitro tests were performed using three bacterial concentrations of pseudomonas aeruginosa. Samples were analyzed from different sites throughout the entire on-line HDF circuit for bacteria endotoxins, fungus and the ability to stimulate whole blood production of tumor necrosis factor-alpha (TNF-alpha). RESULTS: The bacteriological control from the feeding machine water and at the entrance to the monitors had a bacterial level of <100 CFU/mL. No bacteria were detected in the dialysate and endotoxin levels were <0.03 EU/mL. In the in vitro contamination study, with the three bacterial concentrations tested at various points in the circuit, bacterial and fungi were below the level of detection and endotoxins were <0.03 UE/mL. The addition of dialysate samples taken after the 1st microfiltration stage, as well as after the 1st and 2nd ultrafiltration stage and incubated with whole blood were not associated with stimulated TNF-alpha production. CONCLUSIONS: PHF appeared to be a safe and feasible method for on-line HDF even in the unforeseen presence of the bacterial contamination of the feed water or in the water distribution system.

Vitamin E-coated membrane dialyzer and beta2-microglobulin removal.

This study was designed to test the removal of beta2-microglobulin (beta2M) in a vitamin E-modified membrane. We investigated in vivo the dialyzer (Excebrane, series EE, 1.8 m2) with respect to hydraulic permeability (Kuf), maximum ultrafiltration rate (UF max), sieving coefficient (Sc), and solute clearances in hemodialysis (HD) and in soft hemodiafiltration (HDF). Kuf was 18.4 ml/h/mmHg, UF max was 75 ml/min, and Sc for beta2M was 0.45. Clearance values at 400 ml/min of Qb in HD were 258 ml/min for urea, 201 ml/min for creatinine, and 135 ml/min for phosphate. In soft HDF, clearances were slightly higher. beta2M clearance was 26 ml/min in HD and 43 ml/min in soft HDF. In conclusion, Excebrane (series EE) procures a soft HDF with an amount of substitution fluid in post dilution mode of over 60 ml/min. Remarkable small solute clearances were obtained when the blood flow was raised to 400 ml/min. A significant reduction of beta2M is demonstrated by HDF.

[Acute renal failure and thrombotic microangiopathy (TM)]. / Insufficienza renale acuta e microangiopatia trombotica.

BACKGROUND: Thrombotic microangiopathy (TM) is a disorder characterized by fibrin formation and platelet aggregation in the small arteries and capillaries. Two main clinical settings are reported in association with this disorder: hemolitic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Both conditions share common findings such as microangiopathic anemia and thrombocytopenia. HUS is more frequent in children and is mainly characterized by renal symptoms, whereas PTT is dominated by neurologic abnormalities. However, in many patients, the clinical distinction between HUS and PTT is not clear; therefore, some authors consider the two syndromes as manifestations of the same entity. In children, the most common cause of HUS is an enteric infection caused by cytotoxin-producing bacteria (mainly Escherichia coli with serotype O157:H7). This toxin--the Shiga toxin--can bind to glomerular endothelial cells and stimulate the production of cytokines and the secretion of von Willebrand factor (vWf). TM may be caused by drugs such as cyclosporin, tacrolimus, mytomicin C, ticlopidine, quinine, and oral contraceptives. It may be associated with disorders of pregnancy (severe pre-eclampsia and postpartum HUS) or with systemic disorders such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, systemic sclerosis, and human immunodeficiency virus (HIV) infection. Abnormalities of the gene of complement factor H have been found in familial HUS and in some sporadic cases of HUS not associated with diarrhea. Factor H abnormalities induce an uncontrolled complement activation that can activate the coagulation cascade. In familial PTT, genetic abnormalities of the cleaving metalloproteinase of fWf ADAMTS 13 have been identified. In other patients with TTP, antibodies inhibiting this enzyme have been found. As a consequence of plasma ADAMTS 13 deficiency, unusually large vWf multimers are produced. This abnormality, in the presence of an increased shear stress, stimulates platelet adhesion and aggregation. CONCLUSIONS: Knowledge of the type of causative abnormality is relevant to a therapeutic approach. Children with diarrheal HUS usually do not benefit from plasma infusion or exchange, whereas in patients with factor H or ADAMTS 13 deficiency procedures that include the administration of the lacking product and removal of the inhibiting or toxic factors, such as ultralarge vWfs, are mandatory. Potentially renal transplantation candidates should be screened for genetic defects to avoid the recurrence of TM in the graft.

Impact of blood and dialysate flow and surface on performance of new polysulfone hemodialysis dialyzers.

Optimization of hemodialysis treatment parameters and the characteristics of the dialyzer are crucial for short- and long-term outcome of end stage renal disease patients. The new high-flux membrane Helixone in the dialyzer of the FX series (Fresenius Medical Care, Germany) has interesting features, such as the relationship of membrane thickness and capillary diameter which increases middle molecule elimination by convection, as well as higher capillary packing and microondulation to improve the dialysate flow and distribution. Blood flow, dialysate flow and surface area are the main determinants of the performance of a dialyzer, however the impact of each parameter on small and middle molecule clearance in high flux dialysis has not been well explored. In order to find the best treatment condition for the new dialyzer series, we evaluated urea, creatinine, phosphate clearances and reduction rate of beta2-microglobulin in ten stable patients treated with different blood flows (effective Qb 280 and 360 ml/min), dialysate flow (Qd 300 or 500 ml/min) and dialyzer surfaces (1.4 and 2.2 m2, FX60 or FX100). KoA and Kt/V were also calculated. Blood flow, dialysate flow and surface area demonstrated a significant and independent effect on clearance of urea, creatinine and phosphate, as well as on Kt/V. Small solute clearance was stable over the treatment. In contrast to small solutes, reduction rate of beta2-microglobulin was related to increasing dialyzer surface only. The new dialyzer design of the FX series proves highly effective due to improved dialysate distribution and reduced diffusive resistance as shown by the small solute clearance. A high reduction rate of beta2-microglobulin is favored by improved fiber geometry and pore size distribution. These findings have potential long-term benefits for the patient.

[New dialysis therapy modalities: what role do they play in the hemodialysis patient's outcome?]. / Nuovi schemi di terapia dialitica: quale ruolo nell'"outcome" del paziente in emodialisi?

Many studies have been devoted to investigating new techniques and new dialysis strategies aimed at achieving adequate removal of "uremic toxins". Conversely, few studies focus on the effect of different dialysis techniques on long-term outcome, including large series and with adequate follow-up. Dialysis dose, membrane biocompatibility and permeability, convective techniques, and the number and duration of dialysis sessions have all been considered as potentially related to patient outcome. The available data from the literature clearly show a significant relationship between the urea kinetic model based dialysis delivered and long-term patient outcome. A significant positive correlation between survival and Kt/V up to 1.3 per session in patients treated three times a week with standard low flux cellulosic dialyzers has been shown. Many studies have shown an effect of high flux membranes on the appearance of symptoms related to dialysis amyloidosis. It is likely that such an effect is further enhanced by convective or mixed techniques. The role of these techniques in patient survival is suggested by some studies, but should be confirmed in larger series. The use of techniques suitable for ultra-pure dialysis fluids are mandatory whenever high permeability membranes are used. Treatment schedules which include long dialysis sessions or an increased number of sessions such as daily dialysis, seem to be beneficial for the control of hypertension or hyperphosphatemia. However, their role on patient survival has not yet been clearly assessed. Together with the choice of the best strategy, great attention should be paid to other factors known to be related to patient outcome, such as early patient referral, and the type and efficiency of vascular access.

Factors influencing permanent catheter performance.

UNLABELLED: Permanent dual lumen catheters (PDLC) provide an alternative vascular access in patients considered unsuitable for arteriovenous fistula, graft or peritoneal dialysis. However, the use of PDLC is often complicated by inadequate blood flow. The aim of this study was to identify catheter dysfunctions. We studied prospec-tively 57 chronic hemodialyzed patients, 73+/-11 years of age, with PDLC for 18+/-14 (1-48) months. Catheters were tunneled in silicone (MedComp Tesio n= 40) or in polyurethane (Permcath Quinton n = 11, GamCath Gambro n = 6) in left or right internal jugular (n = 49), in left or right subclavian (n = 3) and in right femoral vein (n = 5). We studied the blood viscosity indices (hematocrit, total protein, cholesterol and triglycerides), catheter intra-dialytic parameters (pre-pump and venous pressure), localization of the catheter tip (superior vena cava = SVC, right atrium = RA, inferior vena cava = IVC), blood pressure before and after hemodialysis during the 3 last dialyses, use of anticoagulant (ACT) or antiaggregant therapy (AAT) and previous infectious episodes. The mean blood flow was 269+/-37 ml/min (median 280 ml/min). The patients were divided according to the median value into groups I (Qb < 280, n = 28) and group II (Qb > 280, n =29). RESULTS: Blood viscosity, patients' mean arterial pressure and venous catheter line pressure did not differ between the two groups. Pre-pump pressure, at the start and at the end of treatment, was higher in group I. ACT, AAT and previous infectious episodes could not explain the low-performance. Blood flows of catheters localized in RA, SVC, and in IVC were respectively 287+/-20, 268+/-39, 244+/-27 ml/min. In the first case the Qb was significantly higher than IVC (p = 0.03) and SVC (p = 0.04). In conclusion, the most important factor influencing blood flow rates seems to be the position of the catheter tip in the venous system. The best blood flows were found in catheters with the tip localized in the right cardiac cavities, while PLDC placed in inferior vena cava showed lower blood flow.

Blood flowrate and dialysis adequacy in patients with permanent central venous catheters.

Vascular access efficiency is a major determinant of an adequate dialytic treatment and reports from literature indicates a growing interest in the field of central venous catheterisation as permanent vascular access for hemodialysis. The main reasons are the continuous improvement in design and biomaterials along with the increased number of patients with failure of their vascular beds. In this paper it is presented and commented a series of negative crucial factors which can reduce the quality of the hemodialysis treatment: the problem of re-circulation and the catheter related (and the patient related) causes of inadequate flowrate. Finally the Authors conclude with a short presentation of their clinical experience in the field.

Dialysis prescription in elderly hemodialysis patients.

A growing number of elderly patients have started dialytic treatment in recent years. In spite of this fact, there is very little literature on dialysis prescription in these patients. In this paper, the authors examine the single variables of Kt/V index and report on their own experience when prescribing the dialytic dose in elderly patients. Regarding dialyzer clearance (Kd), it is known that in order to obtain a high Kd we need an adequate vascular access. In our experience, with a radiocephalic fistula elderly patients showed less (but not significantly so) Qac than younger patients (738 +/- 350 ml/min versus 892 +/- 491 ml/min). We can therefore consider this type of fistula as the first vascular access in elderly patients also. As far as Kr is concerned, its rate of decline (0.4+/-0.4 ml/min/month) in these patients, excluding those with diabetes or a history of heart failure, is not different from that of younger patients. Treatment time remains a crucial point for adequacy. In order to avoid hypotensive episodes, especially in the elderly, we suggest T = 180 minutes minimum, and ultrafiltration rates should not exceed 0.6-0.8 kg/h. As regards V, it can be stated that these patients have a reduced lean body mass and total body water, and could therefore require smaller dialysis doses. However, we think that the target of Kt/V in malnourished elderly patients requires further study. What our data on Kt/V delivered to a large group of patients shows is that the elderly received the same adequate dialytic dose (Kt/V > 1.3) as that of younger patients.

The PTH-calcium curve and the set point of calcium in primary and secondary hyperparathyroidism.

BACKGROUND: The regulation of PTH secretion by calcium is altered in patients with primary hyperparathyroidism (HPT). A similar abnormality may occur in secondary HPT, but comparisons of PTH secretion in normal subjects and those with secondary HPT have given contrasting results. Differences in baseline serum ionized calcium (ICa) may partly account for these conflicting results. The aim of the present study was to evaluate whether the regulation of PTH secretion by calcium differs from normal in patients with primary and secondary HPT and to determine whether serum calcium concentration per se can affect the set point of calcium and the PTH-calcium relationship. METHODS: The PTH-ICa relationship and the set point of ICa were evaluated in 19 patients with primary HPT (1-HPT), 16 normocalcaemic patients with secondary HPT (2-HPT; PTH 344+/-191 pg/ml), 19 hypercalcaemic patients with secondary HPT (3-HPT; PTH 806+/-254 pg/ml) and 14 healthy volunteers, by inducing hypocalcaemia and hypercalcaemia in order to maximally stimulate or inhibit PTH secretion. In five 1-HPT patients the PTH-ICa curve was restudied after normalization of serum ICa by pamidronate. Parathyroid gland volume was determined by measuring gland size at parathyroidectomy or by means of high-resolution color Doppler ultrasonography. RESULTS: In 1-HPT patients the PTH-ICa curve, constructed using maximal PTH secretion induced by hypocalcaemia as 100%, was shifted to the right, the set point of ICa was increased, and the slope of the curve was reduced when compared to normal subjects. After normalization of baseline serum ICa by pamidronate, a shift of the PTH-ICa curve towards normal and a reduction in the set point of ICa was observed. However, basal PTH and maximal PTH secretion induced by hypocalcaemia increased, minimal PTH secretion induced by hypercalcaemia remained increased and the slope of the curve did not change significantly. The alterations in the PTH-ICa relationship in hypercalcaemic patients with secondary HPT were similar to those found in 1-HPT patients. In normocalcaemic patients with secondary HPT baseline PTH, maximal and minimal PTH secretion and parathyroid gland size were reduced compared to 3-HPT patients. Compared to normal subjects, 2-HPT patients showed greater calcium-induced minimal PTH secretion. The increase in non-suppressible PTH secretion resulted in a rightward shift of the PTH-ICa curve and an increase in the set point of ICa. A strong correlation was found, in both primary and secondary HPT, between the set point of ICa and baseline serum ICa, and between parathyroid gland size and baseline PTH, maximal PTH and minimal PTH. Multivariate regression analysis showed that baseline serum ICa was the main determinant of the set point of ICa in both primary and secondary HPT. CONCLUSIONS: (i) The regulation of PTH secretion by calcium is abnormal in secondary as well as in primary HPT. (ii) Parathyroid gland enlargement in secondary HPT is associated with reduced sensitivity to serum ICa and resistance of parathyroid gland to calcium-mediated PTH suppression, resulting ultimately in PTH hypersecretion, despite hypercalcaemia. (iii) The set point of calcium is strongly dependent on baseline serum calcium, and the PTH-ICa relationship can be affected by variations in serum ICa concentrations. Thus, when the set point of calcium and the PTH-ICa relationship are evaluated, possible differences in baseline serum ICa concentration among the patients should be taken into account.

BsmI polymorphism of the vitamin D receptor gene in hyperparathyroid or hypoparathyroid dialysis patients.

Since bone mineral density may be influenced by the polymorphisms of the vitamin D receptor (VDR) gene, we studied whether VDR genotypes might drive the progression toward hyperparathyroidism or hypoparathyroidism in patients with end-stage renal disease. On the basis of their parathyroid hormone (PTH) levels, we divided 99 patients undergoing dialysis into 2 groups: 56 patients with hypoparathyroidism (PTH < 104 pg/mL [< 11 pmol/L]) and 43 with hyperparathyroidism (PTH > 261 pg/mL [> 27.5 pmol/L]). The BB polymorphism was more frequent in patients with hypoparathyroidism (34%) than in patients with hyperparathyroidism (16%), but the difference did not reach statistical significance. Patients with the B allele and BB genotype had a significantly lower dialytic age and serum PTH and alkaline phosphatase levels than patients with the b allele and bb genotype. These results suggest that in end-stage renal disease, the BB genotype may mark a higher risk of developing hypoparathyroidism and diminished bone turnover.

In vitro and in vivo biocompatibility of substituted cellulose and synthetic membranes.

Regenerated cellulosic membranes are held as bioincompatible due to their high complement - and leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2 for benzyl-cellulose, 1.8 m2 for acetate-cellulose and low-flux polysulfone. Measurement of leukopenia, plasma C3a des Arg and elastase-alpha1 proteinase inhibitor complex levels as well as urea, creatinine, phosphate and uric acid clearances was performed. Plasma-free neutrophils adhered maximally to acetate-cellulose (65% remaining in the circulation), while there was no significant difference between low-flux polysulfone and benzyl-cellulose (80% circulating neutrophils, at 15 min, p<0.001 vs acetate cellulose). In the presence of fresh plasma, as source of complement, the differences between acetate cellulose vs polysulfone and benzyl-cellulose were even more evident, suggesting the role of complement-activated products in neutrophil adherence. A similar trend was observed for monocyte adherence with the three membranes in the absence or presence of plasma. In vivo studies showed that the nadir of leukopenia was at 15 and 30 min with acetate-cellulose (79%) and benzyl-cellulose (50%) (p<0.05 acetate- vs benzyl-cellulose) and at 15 min with polysulfone (24%) (p<0.01 vs acetate- and benzyl-cellulose). Plasma C3a des Arg levels arose to 2037 +/- 120 ng/ml, 1216 + 434 ng/ml and 46 +/- 55 ng/ml with acetate-, benzyl-cellulose and polysulfone, respectively. No pre- vs post-dialysis increase in the intracellular content of TNF-alpha was detected with any of three membranes. Clearance values of urea, creatinine and uric acid were superimposable for all the three membranes. However, benzyl cellulose had a significantly higher clearance for phosphorus (normalized for surface area) (p<0.01 vs acetate-cellulose, 0.001 vs polysulfone). These results implicate that synthetic modification of the cellulose polymer as for the benzyl-cellulose significantly reduces the in vitro adherence, delays the in vivo activation of "classic" biocompatibility parameters and notably improves the removal of inorganic phosphorus.

Long-term effects of intravenous calcitriol therapy on the control of secondary hyperparathyroidism.

Although high-dose intravenous calcitriol has been shown to be effective in suppressing parathyroid hormone (PTH) secretion in dialysis patients with secondary hyperparathyroidism, an increasing number of patients is refractory to treatment. Only a few studies have evaluated the factors that can predict a favorable response to calcitriol, but contrasting results have been reported. This study was performed to evaluate the effect of high-dose intravenous calcitriol on parathyroid function and to investigate the factors that can predict a favorable response to treatment. Thirty-five dialysis patients were selected for intravenous calcitriol treatment (2 microg after dialysis for 12 months) because of increased PTH levels (>325 pg/mL). Before starting the treatment, the set point of calcium and the PTH-ionized calcium (ICa) curve was evaluated in each patient by inducing hypocalcemia and, 1 week later, hypercalcemia to maximally stimulate or inhibit PTH secretion. Parathyroid glands were assessed by high-resolution color Doppler ultrasonography. Throughout the study, calcium carbonate or acetate dosage was modified to maintain serum phosphate less than 5.5 mg/dL. Hypercalcemia was managed by reducing dialysate calcium to 5 mg/dL and, if necessary, calcitriol dose. The therapeutic goal was to reduce PTH levels below 260 pg/mL while maintaining normocalcemia. The patients who achieved the therapeutic goal were considered responders. Taking the data from the 35 patients together, we observed a significant decrease (P < 0.01) in alkaline phosphatase (from 252 +/- 106 IU/L to 194 +/- 81 IU/L) and PTH (from 578 +/- 231 pg/mL to 408 +/- 291 pg/mL), and a significant increase in serum ICa (from 5.1 +/- 0.2 mg/dL to 5.3 +/- 0.2 mg/dL; P < 0.001) after calcitriol therapy. PTH changes after therapy were not correlated to serum ICa changes, serum phosphate levels during treatment, and calcitriol dose. The response to therapy was heterogeneous because PTH levels markedly decreased over the treatment period in 18 responsive patients, whereas they increased or remained unchanged in 14 of 17 nonresponders. In three additional refractory patients, there was a decline in PTH of 20% to 35%, but this decline was associated with hypercalcemia. Pretreatment parathyroid gland size, serum ICa, PTH, maximal PTH induced by hypocalcemia, minimal PTH induced by hypercalcemia, the set point of ICa, and the ICa levels at which maximal PTH secretion and inhibition occurred were higher in the 17 refractory patients than in the 18 responsive patients. However, logistic regression analysis showed that among these parathyroid function parameters, the only significant predictors of a favorable response to calcitriol therapy were the parathyroid gland size and the set point of ICa. Throughout the study, serum phosphate and calcitriol dose were comparable in the two groups. In conclusion, the response to intravenous calcitriol therapy in dialysis patients with secondary hyperparathyroidism is heterogeneous, consisting of patients who are either responsive or refractory to treatment; refractoriness can be predicted by parathyroid volume and calcium set point.

Protein nitrogen appearance in CAPD patients: what is the best formula?

BACKGROUND: The protein equivalent of nitrogen appearance is an indirect index commonly used to assess dietary protein intake in patients on CAPD. Moreover it has been suggested that the ratio between nitrogen appearance and dietary nitrogen intake (fractional urea synthesis) can predict nitrogen balance in uraemic patients. Several formulae to directly calculate the protein equivalent of nitrogen appearance have been published. It has not been established, however, what formulae give the most appropriate estimate of protein intake and nitrogen appearance. STUDY DESIGN: Nitrogen balance studies were carried out in seven stable patients on CAPD. All of the patients were receiving a diet whose protein content (1.2 g/kg/body wt/day) and calorie content (35 kcal/kg/body wt/day) were rigorously controlled. Six formulae for calculating protein equivalent of nitrogen appearance and nitrogen appearance were tested and the agreement of the estimating formulae was evaluated by means of the Bland and Altman method. RESULT: Net nitrogen balance was 1.68 +/- 0.9 g/N day, protein intake (g/day) 81 +/- 19, protein intake (g/kg) 1.05 +/- 0.17. Differences in protein equivalent of nitrogen appearance of up to about 20% were found. The smallest differences between protein equivalent of nitrogen appearance and protein intake were obtained by the formulae of Bergstrom (1 +/- 7 g, limits of agreement -12 and +15 g) and Blumenkrantz (-2 +/- 5 g, limits of agreement -11 and +7 g). The formula of Bergstrom most closely estimated nitrogen appearance (-0.35 +/- 0.89 g). Using such formula, the fractional urea synthesis was 54 +/- 12%, giving evidence of positive nitrogen balances. CONCLUSION: For the routine monitoring of protein equivalent of nitrogen appearance in CAPD patients, we recommend Bergstrom's formula with the determination of dialysate protein losses.

On-line urea kinetics in haemodiafiltration.

BACKGROUND: Calculation of Kt/V and assessment of nutrition have so far been dependent upon off-line urea measurements of blood or dialysate samples. Here we describe a biosensor for on-line urea measurement during haemodiafiltration. Methods. The biosensor consisted of a cartridge containing covalently linked urease placed between two conductivity cells. The biosensor was placed on the outlet line of a haemofilter in series with a dialyser in order to obtain an aliquot of plasma ultrafiltrate for on-line measurement of urea. RESULTS: Urea nitrogen concentrations were highly correlated to the difference (Delta) in conductivity measured by the two conductivity cells both in aqueous solutions (in-vitro studies, y=-6. 676+32.12x, R2=0.998, P<0.0001) and in ultrafiltrates (ex-vivo studies, y=-637+32.01x, R2=0.98, P<0.00001). Delta conductivity was highly reproducible (% variation: ).8-5.3%) and stable (maximal % variation at 150 mg/dl after 100 min. 0.9+/-0.3 vs initial values). The intradialytic plasma water urea profile was obtained in 10 haemodialysis patients. To study recirculation, the plasma water urea profile was analysed before and 3 min after stopping the dialysate flow. The pre- and post-stopped flow ratio (1.21+/-0.1, mean+/-1 SD) was superimposable to conventional blood sampling data (opposite arm venous arterial: 1.22+/-0.11) and allowed correction for recirculation. A novel approach to urea kinetic modelling was described and used to reliably project end-dialysis and post-dialysis rebound urea concentration as early as 90 min. Projected (29.2+/-10.4 g) or measured (29.8+/-10.5 g) net urea removal was highly correlated with the amount of urea collected in the total spent dialysate (29.7+/-10.6 g) (R2=0.99, R2=0.97 respectively). CONCLUSIONS: These results indicate that on-line, real-time analysis of urea kinetics may provide information on delivery of adequate dialysis in high-efficiency techniques.

Effect of CAPD and hemodialysis on parathyroid function.

UNLABELLED: A high incidence of low turnover bone disease (LTBD) has been reported in predialysis and dialysis uremic patients, despite parathyroid hormone (PTH) levels two- to four-fold the upper normal limit. The aim of this study was to evaluate the trend of PTH in uremic patients after admission to continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD). Thus, we evaluated 53 patients (27 CAPD and 26 HD) of 73 consecutive uremic patients starting CAPD or HD from 1992, who had at least one year follow-up on dialysis. HD and CAPD patients were comparable for age, nephropathy, and duration of uremia. All the patients had been treated with calcium carbonate (CaCO3) as the sole phosphate binder during the predialysis period. At the time of admission to dialysis PTH was > 260 pg/mL (fourfold above the upper normal limit) in 12 CAPD and 9 HD patients, between 130 and 260 pg/mL in 6 CAPD and 5 HD patients, and < 130 pg/mL in 9 CAPD and 12 HD patients. Bone biopsy, performed in 22 patients, showed LTBD in 10 of 12 patients with PTH < 130 pg/mL and high bone turnover in 8 patients with PTH > 260 pg/mL. Patients were treated with a dialysate calcium (Ca) of 1.75 mmol/L and were given CaCO3 to maintain serum phosphate < 5 mg/dL. Oral calcitriol was given if they developed hypocalcemia (< 9 mg/dL). Hypercalcemia (> 10.5 mg/dL) occurred in 13 CAPD and 17 HD patients, and was managed by discontinuation of calcitriol and reduction of dialysate Ca to 1.25-1.5 mmol/L. A significant decrease in PTH and alkaline phosphatase was observed in both groups after six and 12 months of treatment. After one year of CAPD, PTH was > 260 pg/mL in 3 patients, between 130 and 260 pg/mL in 4 (all on calcitriol), and < 130 pg/mL in 20 patients (17 on calcitriol, but only 2 mild hypercalcemic). After one year of HD, PTH was > 260 pg/mL in 3 patients, 130-260 pg/mL in 5 (all on calcitriol), and < 130 pg/mL in 18 (11 on calcitriol, 1 mild hypercalcemic). IN CONCLUSION: (1) about 40% of predialysis patients treated with CaCO3 showed PTH levels suggestive of LTBD; (2) the proportion of patients with low PTH increases after one year on CAPD or HD, even though calcemia was maintained within the normal range; (3) suppressed PTH levels are associated with calcitriol therapy rather than dialysis modality; and (4) secondary hyperparathyroidism improves in most patients after one year on CAPD or HD.