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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.

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.

The aim of this multicenter, prospective, randomized cross-over study was to clarify whether on-line conductivity ultrafiltrate kinetic modeling (treatment B), as a substitute for sodium kinetic modeling, is capable of reducing intradialytic cardiovascular instability in comparison with standard treatment (treatment A), by reducing the sodium balance variability. Both treatments were performed by means of a modified hemodiafiltration technique. Treatment A was performed using fixed dialysate conductivity; treatment B made use of the dialysate conductivity derived from a conductivity kinetic model, in order to obtain an end-dialysis ultrafiltrate conductivity at each dialysis session that was equal to the mean value determined in the same patient during the four-week run-in period. Thus, during treatment B, the expected end-dialysis ultrafiltrate conductivity value of each patient should have been constant. The study was carried out according to a multicenter cross-over design of 16 weeks with two treatments (A or B), two sequences (1 = ABB and 2 = BAA), a run-in period of four weeks (period 1, treatment A), and three consecutive experimental periods of four weeks each. Analysis of variance for a cross-over design was used for the statistical analysis. Forty-nine hemodialysis patients prone to intradialytic hypotension (> 25% of sessions) were enrolled from 16 participating centers, and randomly assigned to either sequence 1 (26 patients) or sequence 2 (23 patients). Six patients dropped out and four were protocol violators, which left 39 patients selected for statistical analysis. There was no difference in the average dialysate conductivity, predialysis and end-dialysis plasma water ultrafiltrate conductivity or body weight between treatment A and treatment B. Thus, the observed mean sodium balance was not different and, as expected, only the intra-patient variability of end-dialysis ultrafiltrate conductivity (index of sodium balance variability) was reduced (21%). During treatment A, systolic blood pressure decreased by 23 mm Hg (95% confidence intervals 21 to 24 mm Hg) at the end of dialysis with respect to the pre-dialysis values. Treatment B reduced this intradialytic decrease (P = 0.001) with a maximum effect at the third hour of dialysis (4.4 mm Hg, 95% confidence intervals 1.9 to 6.9 mm Hg, 23% less than during treatment A, P 0.0005) without any period or carry-over effect (P = 0.53 and 0.08, respectively). There was no treatment effect on intradialytic diastolic blood pressure (P = 0.291). In conclusion, intradialytic cardiovascular stability was significantly improved by matching the interdialytic sodium load with intradialytic sodium removal using on-line conductivity ultrafiltrate kinetic modeling as an alternative to sodium kinetic modeling. Although highly significant, this effect was clinically not very large. By applying this conductivity kinetic model to patients with a more variable sodium intake from one session to another, a greater benefit can be expected.

Background: There are many reports concerning HCV in dialysis patients and most of them conclude that the clinical and biochemical features of hepatitis C are often silent in chronic dialysis patients. Elevated levels of serum alanine aminotransferase activity are a sensitive measure of hepatocellular injury, but so far the relationship between anti-HCV and ALT among chronic dialysis patients has been considered imperfect. To our knowledge, however, such an issue has not been adequately addressed., Methods: Demographic, biochemical, and virological data from 506 patients undergoing chronic dialysis treatment in four dialysis units in Lombardy, northern Italy were collected in order to assess the influence of virological and host factors on serum aminotransferase values., Results: Analysis of covariance showed that positivity for anti-HCV antibody was significantly associated with raised serum AST (P = 0.0001) and ALT (P = 0.0001) levels in the dialysis patients of the whole study group. Logistic regression analysis performed in the subset of patients tested for HCV viraemia and genotype showed that detectable HCV RNA in serum is a strong predictor of raised AST (P = 0.0001) and ALT (P = 0.000001) values. Gender showed an independent weak influence on AST levels (P = 0.055), serum levels of ferritin were significantly (P = 0.042) associated with AST values, the coexistence of HBsAg infection and positivity for anti-HCV antibody was independently associated with raised ALT levels (P = 0.016). The other factors (including positivity for anti-HCV) showed no independent effect on serum aminotransferase levels when they were matched with HCV viraemia in our multivariate analysis. HCV RNA positive patients showed serum AST (P < 0.008) and ALT levels (P < 0.0001) higher than HCV RNA negative patients. There was no relationship between HCV genotypes and liver enzymes., Conclusions: Our data show that detectable HCV RNA in serum is a strong independent predictor of raised aminotransferase values in chronic dialysis patients; the relationship between serum aminotransferase values and anti-HCV antibody was exclusively related to the association between raised aminotransferase values and HCV viraemia; HCV RNA positive patients show higher hepatic enzyme levels than dialysis patients with no detectable HCV RNA; no association between HCV genotype and serum aminotransferase activity was apparent.

Background: It has been calculated that 30% of chronic uraemic patients fail to produce antibodies to HBsAg antigen after hepatitis B (HB) vaccination. Low-dose intradermal (i.d.) inoculations and supplementary intramuscular (i.m.) injections have been reported to improve the response rate in previous non-responder chronic uraemic patients, but no cost-effectiveness evaluations have been made about this issue., Methods: We re-vaccinated 50 chronic dialysis patients, who did not have any detectable anti-HBs antibody after a reinforced protocol of hepatitis B vaccine given by i.m. route, with hepatitis B recombinant DNA yeast vaccine (80 micrograms) by intradermal (25 patients) or intramuscular (25 patients) administration (randomly allocated). We used the same amount of HBsAg in order to exclude the confounding effect of the dose level administered on the immune response of uraemic patients. We studied, over a 20-month follow-up, the persistence of anti-HBs antibodies in our responder vaccinees. We made a comparison between the costs of our re-vaccination protocol and the other re-vaccination strategies that have been recently suggested., Results: One month after completion of re-vaccination protocol, seroconversion rates (100% vs 48%, P = 0.008) and proportion of patients who elicited protective anti-HBs titres (96% vs 40%, P = 0.0001) were significantly higher in i.d. compared to i.m. patients. The levels of anti-HBs expressed as geometric mean titres and 95% confidence intervals (GMT (95% CI)), were significantly increased in i.d. than in i.m. groups, 100 (44-187) vs 26 (14-52) mUI/ml (P = 0.018). At month 12, the seroconversion rates were 57 vs 14% in i.d. and i.m. groups respectively (P = 0.158); the seroprotection rate was higher in i.d. individuals in comparison with i.m. patients, 50 vs 0%, P = 0.072. At month 20, the seroconversion rates were 54 and 0% among i.d. and i.m. patients respectively (P = 0.055); the seroprotection rate was higher in i.d. than in i.m. group (30 vs 0%, P = 0.2). At month 20, the median anti-HBs titres in i.d. patients were 21 mUI/ml, and GMT (95% CI) were 20.9 (2-54) mUI/ml. No important general or local side-effects were observed. The cost of our schedule was $92 US whereas the costs of other re-vaccination protocols ranged between 138 and $807 US., Conclusions: Our results show that the unresponsiveness to recombinant yeast-derived vaccine may be mostly reversed by repeated low-dose i.d. injections of the same agent. In spite of an equal amount of HBsAg received, i.d. hepatitis B re-vaccination shows higher immunogenicity compared to i.m. administration over a 20-month observation period. Cost-effectiveness analysis demonstrated that the intradermal administration of HB vaccine is the most clinically effective re-vaccination strategy; it is also the most unexpensive one. We strongly recommend low-dose intradermal inoculations in order to re-vaccinate chronic dialysis patients who fail to respond to hepatitis B vaccination.

Sodium removal is one of the main factors affecting intradialytic cardiovascular stability and interdialytic hypertension, and its removal should therefore be individualized. The aims of this study were: (1) to test the ability of a single-pool variable volume (SPVV) sodium kinetic model (NaKM) to optimize sodium removal in paired filtration dialysis (PFD), and (2) to test a SPVV conductivity kinetic model (CKM) in order to verify whether CKM can be used as an alternative for NaKM in estimating sodium balance. The mean difference between the NaKM-predicted and measured end-PFD plasma water ionized sodium concentrations was 0.00 +/- 0.55 mEq/l, which means that the model has an imprecision of < or = 1.1 mEq/ l. The mean difference between predicted and measured sodium removal was 0.21 +/- 16.86 mEq/session, which means a model overestimate of 0.21 mEq/session. The mean difference between the CKM-predicted and measured end-PFD ultrafiltrate conductivity was 0.01 +/- 0.05 mS/cm, which means an inaccuracy of the model of 0.01 mS/cm and an imprecision of < or = 0.1 mS/cm. The regression in the ionized sodium concentration measured in plasma or blood on the conductive values of the ultrafiltrate shows an error of < or = 2 mEq/l in the prediction of the ionized sodium concentration in blood by means of ultrafiltrate conductivity measurements. These results demonstrate that both models make it possible to obtain a level of dialytic sodium removal that is almost equivalent to interdialytic sodium loading. Moreover, given that it does not require blood sampling and the possibility of making repeated and inexpensive ultrafiltrate conductivity measurements, the CKM allows online monitoring of programmed sodium removal.

The primary aim of this multicenter, prospective, randomized cross-over study was to clarify whether a new model of hemodialysis (HD) potassium (K) removal using a decreasing intra-HD dialysate K concentration and a constant plasma-dialysate K gradient (treatment B) is capable of reducing the arrhythmogenic effect of standard HD, which has a constant dialysate K concentration and decreasing plasma-dialysate K gradient (treatment A). The secondary aim was to verify whether this new model is clinically safe. In treatment B, the initial dialysate K concentration had to be 1.5 mEq/liter less than the plasma K concentration, and exponentially decrease to 2.5 mEq/liter at the end of HD. Forty-two chronic HD patients with an increase in premature ventricular complexes (PVC) during dialysis were enrolled from 18 participating centers, and randomly assigned to either sequence 1 (ABA) or sequence 2 (BAB). A pool of 333 of 378 expected ECG Holter recordings were checked for signal quality; 269 (71%) from 36 patients (86%) had a satisfactory signal quality and 108 were selected for analysis (1 per patient per period). There was a difference in the natural logarithm of the increase in PVC/hr and PVC couplets/hr during HD between treatments A and B (1.70 +/- 1.59 vs. 1.09 +/- 1.76 and 0.94 +/- 0.86 vs. 0.64 +/- 1.01, a reduction of 36% and 32%, P = 0.011 and 0.047, respectively) without any carry over effect (P = 0.61 and 0.24, respectively). The fact that this decrease of one third is due to a lower plasma-dialysate K gradient is supported by the observation that it was more evident during the first than the last two hours of HD (a reduction in the natural logarithm of the increase in PVC/hr and PVC couplets/hr of 60% and 60%, P 0.002 and 0.009, vs. 26% and 17%, P = 0.098 and 0.332, respectively): the initial plasma-dialysate K gradient was 2.3 times lower during treatment B than during treatment A, without adversely affecting pre-HD plasma K levels. These results could have a considerably clinical impact not only because of the possibility of physiologically decreasing the arrhythmogenic effect of HD, but also because this effect can be considered a "marker" of the electrophysiological derangement induced by the administration of standard HD three times a week for years ("electric disequilibrium syndrome").

The importance of sodium balance avoiding intradialytic cardiovascular instability and interdialytic hypertension and pulmonary edema is well known. An early analytical single-pool kinetic model created to evaluate sodium balance in hemodialysis, using flame photometry to determine plasma and dialysate sodium concentrations, has been shown to have a level of imprecision of +/- 2.8 mEq/l in predicting end-dialysis sodium plasma water concentrations (NaPWt). The ionometric determination of sodium concentrations seems to be more accurate and refers to the activity of the sodium capable of crossing dialysis membranes. On the basis of the theoretical premises of the model mentioned above, we developed a computerized single-pool kinetic model which makes it possible to calculate the ionized dialysate sodium activity (NaDI) required to reach a pre-established target of end-dialysis blood sodium activity (NaBI). Thirty-seven non-diabetic and anuric patients undergoing regular thrice-weekly hemodialysis were given their usual dialysis treatment, with NaDI at the usual value for each patient (range 137-147 mEq/l) and kept constant throughout dialysis. At the beginning and end of the session, NaDI and NaBI were measured in quadruplicate by means of a Nova-1 device (Direct Potentiometry, Pabisch Instruments). The validity of this kinetic model was tested by considering the difference between predicted and observed (P-O) NaBI at the end of dialysis [(t)]. P-O NaBI(t) was -0.37 +/- 0.42 mEq/l, which was statistically different from 0 (p < 0.001). When P-O NaBI(t) was plotted against ONaBI(t), it was more negative at the higher values of ONaBI(t). P-O intradialytic sodium removal (Nag) was -12.5 +/- 17.8 mEq/session, which was also statistically different from 0 (p < 0.001). The imprecision of this kinetic model was less than 0.84 mEq/l, as estimated by doubling the SD of P-O NaBI(t) (0.42 = 0.84 mEq/l). Although the reasons for its inaccuracy especially at higher ONaBI(t) values remain to be clarified, these data are the expression of a satisfactory clinical model.

As cardiovascular stability and the delivery of the prescribed dialysis "dose" seem to be the main factors in determining the morbidity and mortality of hemodialyzer patients today, it is of paramount importance to match hydro-sodium removal with interdialytic load and to verify the delivered dialysis at each session. A specially designed Biofeedback Module (BM--COT Hospal) allows the automatic determination of plasma water conductivity and effective ionic dialysance with no need for blood samples. Using BM, we evaluated the validity of "conductivity kinetic modelling" (CKM) and the possibility that this may substitute "sodium kinetic modelling". Moreover, we evaluated the "in vivo" relationship between ionic dialysance and effective urea clearance. Our results demonstrate that: 1) CKM makes it possible to obtain programmed end-dialysis plasma water conductivity with an error of less than +/- 0.14 mS/cm, roughly equivalent to a sodium concentration of +/- 1.4 mEq/L. 2). Ionic dialysance and effective urea clearance are not equivalent but, as the interrelationship between these is known, the BM allows the routine monitoring of delivered dialysis.

The aim of this study was to evaluate the feasibility and the nutritional and depurative adequacy of the integrated diet dialysis program. The integrated diet dialysis program consists of a low-protein diet (0.4 g/kg ideal body weight/d), supplemented with essential amino acids or a mixture of essential amino acids and chetoanalogues, and once-weekly hemodialysis, tailored to maintain predialytic blood urea nitrogen levels lower than 90 mg/dL. Sixty-nine of 84 recruited patients with a mean age of 62.9 +/- (SD) 11.1 years and a baseline glomerular filtration rate of 2.54 +/- 0.94 mL/min entered the experimental phase; 15 dropped out, eight because of poor diet compliance. At 12-month follow-up, patient and technique survival were, respectively, 89% and 56%. The laboratory, anthropometric, and instrumental parameters of 28 patients with a follow-up of more than 12 months were also evaluated using repeated measures ANOVA. Mean predialytic blood urea nitrogen values were not significantly different (82 +/- 21 mg/dL v 93 +/- 26 mg/dL at baseline and after 12-month follow-up, respectively); total weekly KT/V from residual renal function plus dialysis (1.64 +/- 0.32 v 1.70 +/- 0.29; P = NS) and dialytic index according to Babb and Scribner (1.35 +/- 0.31 v 1.21 +/- 0.33) were stable. No problems were found as far as acid-base, calcium phosphate, water-electrolyte metabolism and blood pressure control are concerned. Body weight, fat free mass, fat, plasma proteins, albumin, and C3 and C4 complement factors were stable. Creatinine production (sum of metabolized plus excreted creatinine) decreased (14.3 +/- 3.2 mg/kg/d v 13.4 +/- 2.6 mg/kg/d; P < 0.05). Transferrin decreased but not significantly (221 +/- 46 mg/dL v 204 +/- 42 mg/dL; P < 0.09). Distal motor conduction velocity from the posterior tibial nerve did not improve during the study (37.8 +/- 4.9 m/s v 36.4 +/- 4.9 m/s), while distal motor conduction velocity from the median nerve worsened (50.8 +/- 4.3 m/s v 46.3 +/- 6.3 m/s; P < 0.05). In conclusion, even though the integrated diet dialysis program may be very important in the psychologically delicate phase between the conservative and the classical three-times-a-week hemodialysis programs, and may also solve some economic and dialytically related organizational problems, it arouses some concern as far as compliance and long-term nutritional and depurative adequacy are concerned. It should therefore be limited to highly motivated patients in centers with well-trained staff or where dialysis facilities are lacking.

Ten healthy volunteers were studied to test the effect of a meat meal on the circadian rhythm of urinary proteins. All subjects were kept at bed-rest during the whole 24-h evaluation period. An oral protein load (0.6 g/kg bodyweight) was given at supper-time (19.00 hours). Urinary and serum samples were collected every 3 h and examined for total protein, albumin, retinol-binding protein, and creatinine. All these variables and glomerular filtration rate (GFR), as measured by creatinine clearance, showed circadian rhythms. Acrophases were located at 14.21 hours (range 11.11-16.25) for urinary total protein, at 17.27 hours (13.14-22.31) for serum total protein, at 15.13 hours (13.01-18.04) for urinary albumin, at 14.18 hours (11.13-19.20) for serum albumin, at 21.22 hours (18.42-02.41) for urinary retinol-binding protein, at 14.51 hours (08.52-19.57) for serum retinol-binding protein, and at 16.17 hours (13.38-19.25) for creatinine clearance. Thus, the acrophases of urinary total protein and urinary albumin excretion rates occurred before the supper protein load, in a time span common to the acrophases of their serum levels and maximal GFR, whereas the acrophase of urinary retinol-binding protein occurred after the supper meat meal, concomitantly with the lowest value of serum retinol-binding protein. These findings suggest that circadian rhythms of urinary total protein and urinary albumin are influenced by changes in GFR, which occur also independently from an oral protein load. In fact, the latter did not modify creatinine clearance when administered at supper time.(ABSTRACT TRUNCATED AT 250 WORDS)