Assessment of intradialysis calcium mass balance by a single pool variable-volume calcium kinetic model.

INTRODUCTION: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single-pool variable-volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. METHODS: Thirty-four patients on thrice-weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end-dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. FINDINGS: The difference between predicted and measured values was 0.02 mmol/L (range -0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD -0.84 ± 1.33 mmol, range -5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. DISCUSSION: The proposed single pool variable-volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.

Optimizing haemodialysate composition.

Survival and quality of life of dialysis patients are strictly dependent on the quality of the haemodialysis (HD) treatment. In this respect, dialysate composition, including water purity, plays a crucial role. A major aim of HD is to normalize predialysis plasma electrolyte and mineral concentrations, while minimizing wide swings in the patient's intradialytic plasma concentrations. Adequate sodium (Na) and water removal is critical for preventing intra- and interdialytic hypotension and pulmonary edema. Avoiding both hyper- and hypokalaemia prevents life-threatening cardiac arrhythmias. Optimal calcium (Ca) and magnesium (Mg) dialysate concentrations may protect the cardiovascular system and the bones, preventing extraskeletal calcifications, severe secondary hyperparathyroidism and adynamic bone disease. Adequate bicarbonate concentration [HCO3 (-)] maintains a stable pH in the body fluids for appropriate protein and membrane functioning and also protects the bones. An adequate dialysate glucose concentration prevents severe hyperglycaemia and life-threating hypoglycaemia, which can lead to severe cardiovascular complications and a worsening of diabetic comorbidities.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

BACKGROUND: Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN: A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS: 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION: AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES: Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS: More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS: A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS: This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.

Hemodiafiltration - state of the art.

Many observational studies have consistently shown that high-flux hemodialysis (hf-HD) has positive effects on the survival and morbidity of chronic kidney disease stage 5 dialysis (CKD5D) patients when compared with low-flux hemodialysis, but the primary analysis of the prospective randomized Hemodialysis Outcomes (HEMO) study showed that the use of hf-HD was not associated with a significant reduction of the relative risk of mortality. More recently, the Membrane Permeability Outcome (MPO) study found that survival could be significantly improved by use hf-HD compared with low-flux dialysis in high-risk patients as identified by serum albumin ≤4 g/dl and, in a post-hoc analysis, in diabetic patients. Online hemodiafiltration (HDF) is reported as the most efficient technique of using high-flux membranes. Clearances of small solutes like urea are higher than in hemofiltration and of middle solutes like ß(2)-microglobulin are higher than in hf-HD. As the number of randomized prospective trials comparing HDF and hf-HD is still very limited, no conclusive data are available concerning the effect of increased convection of online HDF on survival and morbidity in CKD5D patients. A large, randomized controlled study is needed to clinically confirm the theoretical advantages of online HDF.

Management of anemia by convective treatments.

Anemia secondary to chronic kidney disease is a complex syndrome. Adequate dialysis can contribute to its correction by removing small and possibly medium/large molecules that may inhibit erythropoiesis. A clear relationship among hemoglobin, erythropoiesis stimulating agent (ESA) dose and increase in dialysis dose has been pointed out by a number of prospective and retrospective studies. Increasing attention has also been paid to the relationship between dialysis, increased inflammatory stimulus and ESA response, as dialysate contamination and low compatible treatments may increase cytokine production and consequently inhibit erythropoiesis. As medium/large molecular weight inhibitors can be removed only by more permeable membranes, convective treatment sand, particularly, online treatments, could theoretically improve anemia correction by two mechanisms: higher removal of medium and large solutes (possibly containing bone marrow inhibitors) and reduced microbiological and pyrogenic contamination of the dialysate. Unfortunately, available results are conflicting. Large, prospective, randomized studies on this topic are still needed.

Effect of synthetic vitamin E-bonded membrane on responsiveness to erythropoiesis-stimulating agents in hemodialysis patients: a pilot study.

BACKGROUND: Oxidative stress, a recently identified factor related to the response to erythropoiesis-stimulating agents (ESAs), is increased in hemodialysis patients. The aim of this study was to verify whether ESA responsiveness improves if the anti-oxidant vitamin E (Vi-E) is placed on the blood-side layer of a synthetic polysulfone (PS) dialyzer. METHODS: This 8-month, controlled and open randomized study involved 2 groups of patients on stable ESA therapy undergoing hemodialysis using a PS dialyzer with or without Vi-E treatment. Hemoglobin, albumin, high-sensitivity C-reactive protein, interleukin-6, iron status, parathyroid hormone (PTH), Vi-E (alpha- and gamma-tocopherol levels) and the oxidative stress markers, advanced oxidation protein products, carbonyls and advanced glycation end products were evaluated every 2 months. The primary outcome measure was ESA resistance, the weekly ESA dose divided by the product between hemoglobin level and end-dialysis body weight. RESULTS: Nineteen of the 20 randomized patients completed the study. During the follow-up, the ESA resistance significantly decreased (p = 0.024), greater in the Vi-E group (37%) than in the PS group (20%), but this difference was not statistically significant (p = 0.596). Baseline PTH and Vi-E levels were associated with ESA resistance. In the secondary analysis, including these covariates in the model, the difference between groups in ESA resistance became significant (p = 0.042). CONCLUSIONS: Vi-E placed on the blood-side of a dialyzer may have a possible beneficial effect on ESA resistance in hemodialysis patients; baseline PTH levels seem to predict ESA resistance and were useful in showing the possible beneficial effect of Vi-E and should be considered in designing adequate-sized trials for testing this hypothesis.

Can convective therapies improve dialysis outcomes?

PURPOSE OF REVIEW: Convective treatments are characterized by enhanced removal of middle and large molecular weight solutes, important in the genesis of many complications of hemodialysis, compared with conventional low-flux hemodialysis. The availability of these techniques represented an intriguing innovation and a possible means to improve the still poor prognosis of hemodialysis patients. In this study we will critically review the most important published studies evaluating the impact of convective treatments on dialysis outcomes. RECENT FINDINGS: The Hemodialysis (HEMO) study showed that greater urea removal nonsignificantly reduces the relative risk of mortality and that also high-flux hemodialysis was associated with a nonsignificant reduction, although a secondary analysis pointed to an advantage for high-flux membranes in subgroups of patients. More recently, the Membrane Permeability Outcome (MPO) study found that survival could be improved by use of high-flux membranes compared with low-flux dialysis in high-risk patients as identified by serum albumin < or =4 g/dl as well as in people with diabetes. In an observational study, hemodiafiltration with large reinfusion volume has been associated with a lower relative risk of mortality, compared with low-flux hemodialysis. SUMMARY: The biologic plausibility of advantages of convective treatments and the results of the MPO and Dialysis Outcomes and Practice Patterns (DOPPS) studies are supporting rationales for the use of convective treatments to improve survival and delay long-term complications of hemodialysis patients.

Dialysate composition.

The most appropriate dialysate composition is one of the central topics in dialysis treatment. The prescription of a certain dialysate composition could change in order to obtain not only an adequate blood purification but also a high tolerability. Sodium balance represents the cornerstone of cardiovascular stability and good blood pressure control. The goal of dialysis is to remove the amount that has accumulated in the interdialysis period. Potassium removal is adequate when hyperkaliemia is avoided. Bicarbonate in dialysate should be personalized in order to avoid acidosis and end-dialysis excessive alkalosis.

Membrane characteristics.

Dialysis membrane characteristics are important for an effective and biocompatible dialysis. The properties of a membrane determine the size range of uremic toxins that are eliminated, but are also associated to patient morbidity and mortality. In this paper we describe dialysis the membrane characteristics that could influence the choice of a different type of dialysis.

Clinical aspects of haemodiafiltration.

Standard haemodialysis is not a very efficacious treatment of chronic uraemia and patient mortality rate is still very high. The 2002 results of the HEMO study showed that alternative treatments such as 'high-efficiency haemodialysis' and 'high-flux haemodialysis' are associated with a non-significant reduction in the relative risk of mortality (4 and 8%, respectively). In an attempt to define the clinical impact of haemodiafiltration, we review some of the efficacy data from clinical studies in light of a number of factors that may be related to the high mortality among haemodialysis patients.

Effectiveness of sodium and conductivity kinetic models in predicting end-dialysis plasma water sodium concentration: preliminary results of a single-center experience.

The attainment of a neutral sodium balance represents a major objective in hemodialysis patients. It requires that at the end of each dialysis session, total body water volume (V(f)) and total plasma water sodium concentration (Na(pwf)) are constant. Whereas to achieve a constant V(f) it is sufficient that ultrafiltration equals the interdialytic increase in body weight, it is impossible to predict the value of Na(pwf) and calculate the dialysate sodium concentration needed to obtain it without making use of kinetic mathematical models. The effectiveness of both sodium and conductivity kinetic models in predicting Na(pwf) has already been validated in previous clinical studies. However, applying the sodium kinetic model appears to be poorly feasible in the everyday clinical practice, due to the need for blood samples at the start of each dialysis session for the determination of predialysis plasma water sodium concentration. The conductivity kinetic model appears to be more easily applicable, because no blood samples or laboratory tests are needed to determine plasma water conductivity (C(pw)) and ionic dialysance (ID), used in place of plasma water sodium concentration and sodium dialysance, respectively. We applied the 2 models in 69 chronic hemodialysis patients using the Diascan Module for the automatic determination of C(pw) and ID, and using the latter as an estimate of sodium dialysance in the sodium kinetic model. The conductivity kinetic model was shown to be more accurate and precise in predicting Na(pwf) as compared with the sodium kinetic model. Both accuracy and imprecision of the 2 models were not significantly affected by the method used to estimate total body water volume. These findings confirm the conductivity kinetic model as being an effective and easily applicable instrument for the achievement of a neutral sodium balance in chronic hemodialysis patients.

A critical assessment of uremia research.

There are considerably fewer randomized controlled trials investigating hemodialysis (HD) than other fields of internal medicine, and no significant improvements have been observed over time. Only the National Cooperative Dialysis Study and the HEMO trial were based on hard endpoints such as morbidity and mortality, but neither considered on-line hemodiafiltration or super-flux membranes, which are thought to provide a number of advantages in terms of the cardiovascular condition of uremic patients. However, results of well-designed clinical trials showing that increasing convection may improve the clinical outcome of HD patients are still lacking. The need for maximizing removal of uremic toxins calls for more frequent HD sessions, but this may be affected by many organizational problems. Therefore, well-designed, long-term clinical trials are urgently needed to investigate which currently available therapeutic instruments can improve the clinical outcome of uremic patients.

Relationship between urea clearance and ionic dialysance determined using a single-step conductivity profile.

BACKGROUND: On-line determination of ionic dialysance (ID) has been used to measure the clearance of small solutes like urea. However, attempts to determine the in vivo relationship between ID and urea clearance have led to discordant findings. The aim of this study was to determine the relationship between the mean values of repeated instantaneous determinations of ID throughout a dialysis session ((m)ID), obtained using a single-step inlet dialysate conductivity profile, and the mean values of urea clearance corrected for access recirculation (K(eu1)), total recirculation (access plus cardiopulmonary recirculation, K(eu2)), and the entire postdialysis urea rebound (K(wb)). METHODS: Eighty-two anuric patients on chronic thrice-weekly hemodialysis were studied using an Integra machine equipped with the Diascan module for the automatic determination of ID. The mean values of repeated ID measurements made at 30-minute intervals were compared with K(eu1) (available for only 31 patients), K(eu2), and K(wb). RESULTS: The results in all 82 patients were: (m)ID = 176 +/- 23 mL/min; K(eu2) = 181 +/- 25 mL/min; K(wb) = 159 +/- 22 mL/min. The mean (m)ID/K(wb) and (m)ID/K(eu2) ratios were, respectively, 1.11 +/- 0.06 and 0.98 +/- 0.06. The results in the 31 patients for whom K(eu1) values were available were: (m)ID = 179 +/- 24 mL/min and K(eu1) = 200 +/- 27 mL/min; the mean (m)ID/K(eu1) ratio was 0.90 +/- 0.05. CONCLUSION: The mean value of repeated ID determinations obtained using a single-step conductivity profile underestimates urea clearance corrected for access recirculation, and may be considered an adequate estimate of urea clearance corrected for total recirculation.

Mini-peritoneal equilibration test: A simple and fast method to assess free water and small solute transport across the peritoneal membrane.

BACKGROUND: Loss of ultrafiltration (UF) of peritoneal membrane is one of the most important causes of peritoneal dialysis failure. UF is determined by osmotic forces acting mainly across small pores (UFSP) and ultrasmall pores or free water transport. At present, only semiquantitative estimates or complicated computer simulations are available to assess free water transport. The aim of this study was to assess free water transport during a 3.86% peritoneal equilibration test lasting 1 hour. In this condition, sodium transport is mainly due to convection, allowing the estimate of ultrafiltration of small pores and then of free water transport (total UF - UFSP). METHODS: In 52 peritoneal dialysis patients we performed a 3.86% peritoneal equilibration test (4 hours) and a 3.86% mini-peritoneal equilibration test (1 hour) and compared UF and small solute transports obtained with the two methods. RESULTS: During the 3.86% mini-peritoneal equilibration test, UFSP and free water transport were 279 +/- 142 mL and 215 +/- 86 mL, respectively; free water transport well correlated to total UF during the 3.86% peritoneal equilibration test (r= 0.67). The groups of peritoneal transporters, categorized according to glucose dialysate ratio (D/D(0)) and to creatinine/plasma ratio (D/P(Creat)), were in good agreement for the two peritoneal equilibration tests (weighted kappa 0.62 and 0.61, respectively). CONCLUSION: The 3.86% mini-peritoneal equilibration test is a simple and fast method to assess free water transport. It also gives information about total UF and small solute transports and it is in good agreement with the 3.86% peritoneal equilibration test.

Long-term outcome in hemodialysis: morbidity and mortality.

Despite technical and pharmacological improvements achieved over the past years, long-term prognosis of patients undergoing chronic hemodialysis is still rather poor. Cardiovascular disease is the leading cause of both morbidity and mortality in these patients, mostly because of their severely compromised cardiovascular conditions already at the time of starting hemodialysis. A proper management of factors involved in the development of cardiovascular abnormalities is therefore a basic pre-requisite for improving their clinical outcome. Hypertension and anemia should be adequately evaluated and corrected, in light of their primary involvement in the pathogenesis of left ventricular hypertrophy, whereas treatment of calcium and phosphate metabolism disorders, particularly of high serum phosphorus levels, is needed to prevent the development of severe secondary hyperparathyroidism and mainly vascular calcifications, whose detrimental pathophysiologic consequences on cardiovascular structures are huge. At the same time, the prescription of the hemodialytic treatment should be optimised, with a satisfactory removal of uremic toxins through the delivery of an adequate dialysis dose and with the use of biocompatible membranes, where possible, thus minimizing the inflammatory response secondary to the interaction between blood and the artificial material of the hemodialysis system. The clinical superiority of high-flux membranes, although suggested by all studies performed so far, has still to be demonstrated by well-conducted clinical studies; on-line convective treatments and daily hemodialysis, although promising, also need to be confirmed in randomized trials. In conclusion, long-term outcome of hemodialysis patients may only be improved by a complex, multi-factorial therapeutical approach.

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients.

BACKGROUND: An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance. METHODS: Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (U(pwt2')). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric hemodialysis patients were studied. RESULTS: V(DDQ) was 26.3 +/- 5.2 L; V(ID) was 26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3 +/- 3.3 L, which is statistically significant (P < 0.001). CONCLUSION: Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.