Salvatore Di Filippo

Optimization of Sodium Removal in Paired Filtration Dialysis by Single Pool Sodium and Conductivity Kinetic Models

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.

Sodium Kinetics Across Dialysis Membranes

The kinetics of sodium across dialysis membranes were studied during diffusion and during convection utilizing cuprophan and cellulose hydrate membranes. During diffusion the changes in plasma water sodium concentration are correlated to the sodium concentration gradient between plasma water and dialysate but an increase also occurs when the gradient is annulled, due to the Donnan effect. During convection the plasma water sodium concentration increases during the passage through the dialyzer and the ultrafiltrate sodium concentration is significantly lower than the plasma water sodium concentration; this is due to the fact that the plasma proteins, as anions unable to cross the membrane, affect the kinetics of the sodium cations. Therefore, during diffusion the kinetics of sodium are mainly affected by the sodium concentration gradient and by the plasma protein concentration, while during convection the plasma protein concentration is the main factor affecting the kinetics of sodium.

Supplemented Low-Protein Diet and Once-Weekly Hemodialysis

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.

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 (α- and γ-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.

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.

Sodium Kinetics During Dialysis

Despite technological advances, cardiovascular instability still affects a large percentage of uremic patients undergoing extracorporeal substitutive programs. Although the pathogenesis of this instability is multifactorial, growing importance is ascribed to the progressive increase in the age and comorbid conditions of patients starting substitutive therapy, the median dialytic age and comorbid conditions of existing patients, and the tendency to shorten dialysis treatment time by means of higher blood flows, larger dialyzer surfaces, and greater ultrafiltration rates. Since little can be done concerning the epidemiological factors, and economic reasons and patient wishes make it difficult to lengthen the duration of dialysis sessions, particular emphasis now has to be placed on other possible means of improving cardiovascular stability. It has long been known that dialysate sodium concentration is one of the main factors affecting intradialytic cardiovascular stability, and so sodium dialysate concentrations have been progressively increased. However, although this is effective in reducing intradialytic morbidity, the systematic use of higher sodium concentrations is not without its disadvantages (hypertension and pulmonary edema), particularly as sodium balance is infrequently checked. Hemofiltration and hemodiafiltration have been reported to be alternative methods of improving cardiovascular stability, possibly because their effects on peripheral resistance are different from those of hemodialysis (1–3). However, the lower morbidity rates reported for hemofiltration may be at least partially due to the fact that, under conditions of usual use, it removes less sodium than hemodialysis (4) and so has the same potential side effects as those mentioned above. Consequently, not only the sodium concentration of the dialysate but also that of reinfusion fluids has to be taken into account when convective techniques are used and, given the close relationship between morbidity and dialytic sodium removal, any comparison of different dialytic strategies should include the assessment of sodium flux.

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.

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 patients 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.

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 (Vf) and total plasma water sodium concentration (Napwf) are constant. Whereas to achieve a constant Vf it is sufficient that ultrafiltration equals the interdialytic increase in body weight, it is impossible to predict the value of Napwf 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 Napwf 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 (Cpw) 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 Cpw 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 Napwf 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.

Opinion: Can Chronic Volume Overload Be Recognized and Prevented in Hemodialysis Patients?

Hypertension is very common in dialysis patients: according to the Dialysis Outcome and Practice Pattern Study, its prevalence is 83% in United States, 73% in Europe, and 56% in Japan (1). It is largely a consequence of an expanded extracellular volume resulting from a positive sodium balance (2), although sympathetic nervous activity, renin-angiotensin system, cardiac function, and vascular resistance are also to be considered. It is not easy to estimate the absolute value of extracellular volume and its compartments (blood and interstitial volume), but somemethods ofmonitoring hydration in hemodialysis patients have been developed and are discussed in the following paragraphs.