Dialysis Bath Research Articles

Five Decades of Indian Nephrology: A Personal Journey

Impressive accomplishments have been made in Indian nephrology during the last 5 decades. The first renal biopsy performed in 1956 ushered in a new era of modern nephrology practice in India and led to the recognition of nephrology as a distinct specialty. The first hemodialysis facility was established in 1961; presently, there are 950 nephrologists, 850 hospitals equipped with dialysis facilities, and 170 institutions recognized for kidney transplantation, with approximately 3,500 transplantations performed every year. The majority of dialysis units are small minimal-care facilities with fewer than 5 dialysis stations, and more than 85% are in the private sector. Government hospitals provide free treatment to poor patients with chronic kidney disease; however, inadequate funding and lack of health insurance schemes pose serious hurdles in providing renal replacement therapy. In contrast, private/corporate hospitals located in big cities have large units with state-of-the-art dialysis and transplantation facilities, similar to advanced centers of the world, but are accessible to only upper-income groups. Of the estimated 175,000 new patients who develop end-stage renal disease annually, less than 10% are able to gain access to renal replacement therapy. Research in the field of renal diseases has evolved slowly and is focused primarily on tropical conditions. The availability of structured nephrology training programs coupled with excellent diagnostic and therapeutic facilities in some academic institutions and tertiary-care private/corporate hospitals have diminished the need for foreign travel by students, patients, and consultants to a considerable extent. The expansion of therapeutic facilities in India is hampered by only economic constraints, not lack of expertise.

A Tribute to Willem Johan Kolff, M.D., 1912–2009

Willem J. Kolff, M.D., 97, inventor of the first artificial organ to reliably sustain life, died of congestive heart failure on February 11, 2009, in Newtown Square, PA. Dr. Kolff is widely considered the “father of artificial organs.” His rotating drum artificial kidney was initially reported in 1943 and, for the first time, offered an effective intervention for the treatment of acute renal failure.1 It was in The Netherlands during World War II at the height of German occupation that he began work on the first dialysis machine. He had moved to a small hospital in Kampen, on the Zuider Zee, to escape the Nazi sympathizers who had been put in charge of his hospital at Groningen. There, conducting bench experiments with sausage casing (Visking Casing Corporation), saline, and urea, he saw that urea moved down its concentration gradient and equilibrated across this cellulosic membrane. He then cobbled together his rotating drum artificial kidney from miscellaneous available parts including bed slats, a bathtub, and sundry tubing connectors of considerable sophistication. It is the only artificial kidney where uremic blood is circulated through tubing that itself is moving through a stationary noncirculating dialysis bath. The membrane area employed was 2 to …

Induction of NO synthase 2 in ventricular cardiomyocytes incubated with a conventional bicarbonate dialysis bath

In hypotension-prone patients, conventional bicarbonate dialysis (BD) causes a reduced cardiovascular tolerance to the treatment with respect to acetate-free biofiltration (AFB). One possible explanation is an overproduction of endogenous NO (nitric oxide) due to the residual quote of acetate (4 mM) in the BD dialysate formulation. NO overload might cause the impairment of cardiovascular reactivity observed during BD. In this study, a potential direct impact of the residual quote of acetate on the cardiac cells was investigated. Ventricular cardiac myocytes isolated from adult rat hearts were treated with three different dialysis baths with or without acetate: BD, AFB and AFB + 4 mM of acetate (AFB(+)). Corresponding levels of expression of the inducible NO synthase 2 (NOS2) were assessed after the treatments along with the measurement of single-cell action potential (AP). Incubation with acetate-containing dialysis solutions significantly enhanced (P < 0.05) the expression of NOS2 mRNA (BD: 1.11 +/- 0.31; AFB(+): 0.73 +/- 0.04, NOS2/GAPDH intensitometric ratio) with respect to the acetate-free bath (AFB: 0.03 +/- 0.01). Accordingly, protein translation was also enhanced (BD: 0.176 +/- 0.021; AFB(+): 0.135 +/- 0.009, NOS2/alpha-tubuline intensitometric ratio) with respect to AFB (0.002 +/- 0.001, P < 0.05). Measurement of the AP indicates that acetate-containing solutions determine a shortening of the repolarization phase as compared to treatment with AFB (BD: 95 +/- 13; AFB(+): 76 +/- 10; AFB: 162 +/- 16 ms). These findings show that the residual quote of acetate of the BD bath formulation affects the expression of NOS2 and the duration of AP in cardiac cells. This might cause the cardiac contractile impairment in unstable patients during BD treatment.

Electrolyte concentration during haemodialysis and QT interval prolongation in uraemic patients

To assess the effect of different combinations of potassium and calcium concentrations on QT interval in the dialysis bath in uraemic patients. Sixteen haemodialysis (HD) patients underwent a 24 h Holter recording before and during HD sessions with six randomized combinations of electrolytes concentrations of the dialysis bath (K(+), 2 and 3 mmol/L; Ca(2+), 1.25, 1.5, and 1.75 mmol/L). The effect of different dialysis baths on QT interval was significant (P < 0.05). The longest mean QTc was observed with the lowest K(+) (2 mmol/L) and Ca(2+) concentrations (1.25 mmol/L), whereas the shortest mean QTc was observed with the highest K(+) (3 mmol/L) and Ca(2+) concentrations (1.75 mmol/L). QTc was >440 ms in 9 of 16 patients (56%) at the lowest Ca(2+) and K(+) concentrations, and in 3 of 16 patients (18%) at the highest electrolytes level. Changes in QTc during the HD sessions were inversely correlated with that in total Ca and Ca(2+) plasma concentrations (P < 0.0001). Changes in ventricular repolarization duration associated with HD largely depend on the concentrations of Ca(2+) and K(+) in the dialysis bath. These findings may have important implications for the choice of the electrolytes concentration of the dialysis bath during the HD session.

Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial

BackgroundMagnesium salts bind dietary phosphorus, but their use in renal patients is limited due to their potential for causing side effects. The aim of this study was to evaluate the efficacy and safety of magnesium carbonate (MgCO3) as a phosphate-binder in hemodialysis patients.MethodsForty-six stable hemodialysis patients were randomly allocated to receive either MgCO3 (n = 25) or calcium carbonate (CaCO3), (n = 21) for 6 months. The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO3 group and 0.48 mmol/l in the CaCO3 group.ResultsOnly two of 25 patients (8%) discontinued ingestion of MgCO3 due to complications: one (4%) because of persistent diarrhea, and the other (4%) because of recurrent hypermagnesemia. In the MgCO3 and CaCO3 groups, respectively, time-averaged (months 1–6) serum concentrations were: phosphate (P), 5.47 vs. 5.29 mg/dl, P = ns; Ca, 9.13 vs. 9.60 mg/dl, P < 0.001; Ca × P product, 50.35 vs. 50.70 (mg/dl)2, P = ns; Mg, 2.57 vs. 2.41 mg/dl, P = ns; intact parathyroid hormone (iPTH), 285 vs. 235 pg/ml, P < 0.01. At month 6, iPTH levels did not differ between groups: 251 vs. 212 pg/ml, P = ns. At month 6 the percentages of patients with serum levels of phosphate, Ca × P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines were similar in both groups, whereas more patients in the MgCO3 group (17/23; 73.91%) than in the CaCO3 group (5/20, 25%) had serum Ca levels that fell within these guidelines, with the difference being significant at P < 0.01.ConclusionOur study shows that MgCO3 administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients. The administration of MgCO3 in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia.

Experimental Therapies in Renal Replacement: The Effect of Two Different Potassium Acetate‐free Biofiltration Protocols on Striated Muscle Fibers

Dramatic removal of potassium during hemodialysis sessions can induce changes in the electrical properties of nerve cells or muscle fibers, which may underlie neuromuscular symptoms referred by end-stage renal disease patients. The primary aim of our study was to investigate the effects of acetate-free biofiltration (AFB) on the amplitude of compound motor action potential (cMAP) obtained after stimulation of the ulnar nerve at the wrist. The secondary aim was to compare the effect of two different potassium removal modalities on cMAP amplitude and to analyze the effects on muscular force by specific dynamometric tests. Twenty-eight patients received dialysis for 4 h, 3 times per week, first with standard AFB with constant potassium (AFB) and then with AFB with a variable concentration of potassium in the dialysis bath (AFB(K)). The amplitude of cMAP was determined after ulnar nerve stimulation at the wrist at different time intervals: at the start of dialysis; at 15, 45, 90, and 120 min after beginning the session; and at the end of treatment. At the same time intervals, muscle force generation was determined using a dynamometer. Finally, we measured plasma electrolytes, intraerythrocytic potassium, and the electrical membrane potential at rest (REMP) of the erythrocytic membrane. The main finding of this study was a significant reduction of cMAP amplitude in the first 45 min after AFB, which paralleled the reduction in serum potassium levels. Moreover, there was a reduction of muscular strength determined with dynamometric measurements. Potassium removal induced by the two different modalities of AFB may significantly affect myocardial and fibromuscular cells by modulating the electrochemical balance of cell membranes. The transient alteration of the electrical properties on voluntary striated muscle fibers may contribute to the brief reduction in muscular strength we detected in patients who underwent AFB. AFB(K) can minimize the negative effects of standard AFB treatment on neuromuscular excitability, most likely through a more gentle variation of potassium levels during dialysis.

Serum and Dialysate Potassium Concentrations and Survival in Hemodialysis Patients

Controlling serum potassium is an important goal in maintenance hemodialysis patients. We examined the achievement of potassium balance through hemodialysis treatments and the associated fluctuations in serum potassium. A 3-yr (July 2001 to June 2004) cohort of 81,013 maintenance hemodialysis patients from all DaVita dialysis clinics across the United States were studied. Nine quarterly-averaged serum potassium groups (< 4.0, > or = 6.3 mEq/L and seven increments in-between) and four dialysate potassium concentration groups were created in each of the 12 calendar quarters. The death risk associated with predialysis potassium level and dialysate potassium concentration was examined using unadjusted, case-mix adjusted, and malnutrition-inflammation-adjusted time-dependent survival models. Serum potassium correlated with nutritional markers. Serum potassium between 4.6 and 5.3 mEq/L was associated with the greatest survival, whereas potassium < 4.0 or > or = 5.6 mEq/L was associated with increased mortality. The death risk of serum potassium > or = 5.6 mEq/L remained consistent after adjustments. Higher dialysate potassium concentration was associated with increased mortality in hyperkalemic patients with predialysis serum potassium > or = 5.0 mEq/L. A predialysis serum potassium of 4.6 to 5.3 mEq/L is associated with the greatest survival in maintenance hemodialysis patients. Hyperkalemic patients who undergo maintenance hemodialysis against lower dialysate bath may have better survival. Limitations of observational studies including confounding by indication should be considered when interpreting these results.

Comparison between different dialysate calcium concentrations in nocturnal hemodialysis

Benefits of dialysate with greater calcium (Ca) concentration are reported in nocturnal hemodialysis (NHD) to prevent Ca depletion and subsequent hyperparathyroidism. Studies with patients dialyzing against 1.25 mmol/L Ca baths demonstrate increases in alkaline phosphatase (ALP) and parathyroid hormone (PTH) and increasing dialysate Ca subsequently corrects this problem. However, whether 1.5 or 1.75 mmol/L dialysate Ca is most appropriate for NHD is yet to be determined, and differences in the effect on mineral metabolism of daily vs. alternate daily NHD have also not been well defined. We retrospectively analyzed mineral metabolism in 48 patients, from 2 institutions (30 at Monash and 18 at Geelong), undergoing home NHD (8 hr/night, 3.5-6 nights/week) for a minimum of 6 months. Thirty-seven patients were dialyzed against 1.5 mmol/L Ca bath and 11 patients against 1.75 mmol/L. We divided patients into 4 groups, based on dialysate Ca and also on the hours per week of dialysis, <40 (1.5 mmol/L, n=29 and 1.75 mmol/L, n=8) or > or =40 (n=4 and 7). We compared predialysis and postdialysis serum markers, time-averaged over a 6-month period, and the administration of calcitriol and Ca-based phosphate binders between 1.5 and 1.75 mmol/L Ca dialysate groups. Baseline characteristics between all groups were similar, with a slightly longer, but nonsignificant, duration of NHD in both 1.75 mmol/L dialysate groups compared with 1.5 mmol/L. The mean predialysis Ca, phosphate, and Ca x P were similar between the 1.5 and 1.75 mmol/L groups, regardless of NHD hr/week. Postdialysis Ca was significantly greater, with 1.75 vs. 1.5 mmol/L in those dialyzing <40 hr/week (2.64+/-0.19 vs. 2.50+/-0.12 mmol/L, p=0.046), but postdialysis Ca x P were similar (2.25+/-0.44 vs. 2.16+/-0.29 mmol(2)/L(2), p=0.60). Parathyroid hormone was also lower with 1.75 vs. 1.5 mmol/L baths in the <40 hr/week groups (31.99+/-26.99 vs. 14.47+/-16.36 pmol/L, p=0.03), although this difference was not seen in those undertaking NHD > or =40 hr/week. Hemoglobin, ALP, and albumin were all similar between groups. There was also no difference in vitamin D requirement when using 1.75 mmol/L compared with the 1.5 mmol/L dialysate. Multivariate analysis to determine independent predictors of postdialysis serum Ca showed a statistically significant positive association with predialysis Ca, dialysate Ca, and total NHD hr/week. An elevated dialysate Ca concentration is required in NHD to prevent osteopenia but differences in serum markers of mineral metabolism between 1.5 and 1.75 mmol/L Ca dialysate in NHD in our study were few. This was similar for patients undertaking NHD <40 or > or =40 hr/week, although differences in the frequency of NHD may also be as important as dialysate Ca with regard to serum Ca levels. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown and further studies addressing bone metabolism with larger NHD numbers are required.

Vasopressin administration facilitates fluid removal during hemodialysis

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Treatment of post-dialytic orthostatic hypotension with an inflatable abdominal band in hemodialysis patients

The purpose of this study was to ascertain whether abdominal compression with an inflatable abdominal band, a device we developed, improved post-dialytic orthostatic hypotension (OH) in hemodialysis (HD) patients. Twenty-five chronic HD patients with intractable post-dialytic OH were recruited. Post-HD changes in systolic blood pressure (DeltaSBP) in the supine and standing positions were compared in the patients, measured with or without the use of the band. The study showed DeltaSBP after HD without the band was significantly greater than that measured before HD (-36.1+/-18.2 vs -13.1+/-16.8 mm Hg; P<0.0001). DeltaSBP after HD with the band was reduced significantly in comparison to DeltaSBP after HD without the band (-19.4+/-21.2 vs -36.1+/-18.2 mm Hg; P<0.002). Use of the band did not cause an elevation in SBP in the supine position (149.0+/-29.6 vs 155.4+/-25.7 mm Hg); however, it did increase SBP upon standing (129.6+/-27.3 vs 117.2+/-22.6 mm Hg; P<0.05). Eight patients in whom an increase in SBP of 25 mm Hg or more was achieved with the band were classified as responders. Ejection fraction was significantly higher (76.4+/-11.1 vs 61.9+/-13.6%; P<0.02) and atrial natriuretic peptide concentration significantly lower (27.9+/-22.0 vs 68.9+/-47.5 pg/ml; P<0.02) in responders than in non-responders. We conclude that the abdominal band was effective for overcoming post-dialytic OH, without elevating supine SBP in some patients.

Calcium phosphate metabolism and bone mineral density with nocturnal hemodialysis

An elevated calcium x phosphate product (Ca x P) is an independent risk factor for vascular calcification and cardiovascular death in dialysis patients. More physiological dialysis in patients undergoing nocturnal hemodialysis (NHD) has been shown to produce biochemical advantages compared with conventional hemodialysis (CHD) including superior phosphate (P) control. Benefits of dialysate with greater calcium (Ca) concentration are also reported in NHD to prevent Ca depletion and subsequent hyperparathyroidism, but there are concerns that a higher dialysate Ca concentration may contribute to raised serum Ca levels and greater Ca x P and vascular disease. The NHD program at our unit has been established for 4 years, and we retrospectively analyzed Ca and P metabolism in patients undergoing NHD (8-9 h/night, 6 nights/week). Our cohort consists of 11 patients, mean age 49.3 years, who had been on NHD for a minimum of 12 months, mean 34.3 months. Commencement was with low-flux (LF) NHD and 1.5 mmol/L Ca dialysate concentration, with conversion to high-flux (HF) dialyzers after a period (mean duration 18.7 months). We compared predialysis serum albumin, intact parathyroid hormone, P, total corrected Ca, and Ca x P at baseline on CHD, after conversion to LF NHD and during HF NHD. We also prospectively measured bone mineral density (BMD) on all patients entering the NHD program. Bone densitometry (DEXA) scans were performed at baseline (on CHD) and yearly after commencement of NHD. With the introduction of HF dialyzers, the Ca dialysate concentration was concurrently raised to 1.75 mmol/L after demonstration on DEXA scans of worsening osteopenia. Analysis of BMD, for all parameters, revealed a decrease over the first 12 to 24 months (N = 11). When the dialysate Ca bath was increased, the median T and Z scores subsequently increased (data at 3 years, N = 6). The mean predialysis P levels were significantly lower on LF NHD vs. CHD (1.51 vs. 1.77 mmol/L, p = 0.014), while on HF NHD P was lower again (1.33 mmol/L, p = 0.001 vs. CHD). Predialysis Ca levels decreased with conversion from CHD to LF NHD (2.58 vs. 2.47 mmol/L, p = 0.018) using a 1.5 mmol/L dialysate Ca concentration. The mean Ca x P on CHD was 4.56 compared with a significant reduction of 3.74 on LF NHD (p = 0.006) and 3.28 on HF NHD (p = 0.001 vs. CHD), despite the higher dialysate Ca in the latter. We conclude that an elevated dialysate Ca concentration is required to prevent osteopenia. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown. Better P control on NHD, however, reduces the overall Ca x P, despite the increased Ca concentration, therefore reducing the risk of vascular calcification.

The Use of Parenteral Nutrition in a Severely Malnourished Hemodialysis Patient With Hypercalcemia

There is a high prevalence of protein-energy malnutrition (PEM) in chronic dialysis patients. Causes of PEM include the catabolic effects of hemodialysis treatments, acidemia associated with end-stage renal disease, common comorbid conditions, and uremia-induced anorexia. Morbidity and mortality increase with PEM. Before considering parenteral nutrition (PN) as a nutrition intervention in a maintenance dialysis patient, all other efforts to promote optimal nutrition need to be exhausted. The first step is careful evaluation of protein-energy status, followed by intensive nutrition counseling. If necessary, this is followed by oral nutrition supplementation, appetite stimulation, enteral tube feedings, and finally PN. Short-term parenteral nutrition (PN) became a crucial component of the management of a 38-year-old hemodialysis (HD) patient who endured serious complications after kidney transplant rejection. A profound and prolonged malnourished state followed her treatment for necrotizing pancreatitis. She had developed persistent hypercalcemia believed secondary to tertiary hyperparathyroidism (HPT) and immobilization. Later, she developed hungry bone syndrome (HBS) after parathyroidectomy (PTX). She also developed refeeding syndrome after initiation of PN. The patient's persistent, poorly understood hypercalcemia did not resolve even after PTX and removal of all other sources of vitamin D and calcium from her feedings, medications, and dialysis bath. The close communication of the inpatient and outpatient dialysis multidisciplinary teams became a key component to the successful outcome in this complex patient.

Once-weekly intravenous paricalcitol in the treatment of secondary hyperparathyroidism in hemodialysis patients

Paricalcitol, a vitamin D analog, is commonly administered three times weekly to control secondary hyperparathyroidism in hemodialysis patients. Less frequent dosing would be more convenient, require less nursing time, and be an option in other dialysis modalities. No studies have examined the efficacy of once-weekly dosing of paricalcitol. Chronic hemodialysis patients receiving a stable dose of paricalcitol three times weekly with intact PTH (iPTH) 100-500 ng/l were monitored during a two-week baseline, then were converted to a single mid-week paricalcitol dose equal to the previous cumulative weekly dose. Serum calcium and phosphorus were monitored weekly and iPTH levels determined during study Weeks 4 and 8. A single paricalcitol dose adjustment was made during study Week 5 based on iPTH to achieve a target value of 150-300 ng/l. Phosphate binders and calcium dialysate bath were kept constant during the study. In the 25 patients, mean iPTH was 295 +/- 107 ng/l at baseline, and not significantly different at Week 4 (307 +/- 111 ng/l) or Week 8 (285 +/- 98 ng/l). Paricalcitol dose increases mid-study were almost exclusively in patients with iPTH > 300 ng/l. Calcium, phosphorus, and calcium x phosphorus product were not significantly different on weekly therapy. (Only one patient developed a calcium > 2.55 mmol/l during the study.) Once-weekly dosing of paricalcitol is an effective option in treatment of secondary hyperparathyroidism. Less frequent dosing may better allocate nursing time and potentially benefit other patient populations with CKD and ESRD.

The effect of two different protocols of potassium haemodiafiltration on QT dispersion

The risk of developing cardiovascular diseases is higher in patients on haemodialysis than in the general population. These patients may develop arrhythmias that depend on the extra- and intracellular concentrations of potassium. ECG findings, particularly the QT interval and its dispersion (QT(d)) and the QT(c) (QT interval corrected for heart rate according to Bazett's formula) and its dispersion (QT(cd)), may be direct indicators of the risk of developing arrhythmia. Our cohort comprised 28 patients who were dialysed for 3.5-4 h three times per week, first with haemodiafiltration with a constant potassium concentration (HDF) in the dialysis bath then with haemodiafiltration with variable concentrations of potassium (HDF(k)). ECGs were done at different time intervals: at the start of dialysis (T(0)), at 15 (T(15)), 45 (T(45)), 90 (T(90)) and 120 min (T(120)) after the beginning of the session, and at the end of treatment (T(end)). ECG-derived data (QT, QT(d), QT(c) and QT(cd)) were measured. At the same time points, plasma electrolytes, intra-erythrocytic potassium and the electrical membrane potential at rest (REMP) of the erythrocytic membrane were measured. Plasma potassium concentration diminished more gradually in HDF(k) than in HDF, the difference being statistically significant at T(15) and T(45) (P<0.05), and T(90) (P<0.01). The intra-erythrocytic potassium concentration remained constant throughout the observation period. In both HDF and HDF(k), REMP was lower at all points after T(0) (P<0.05), but the reduction was greater and more significant in HDF than in HDF(k) at T(15) and T(120) (P<0.05). ECG revealed a statistically significant diminution in HDF(k) vs HDF in the measures of dispersion of QT and QT(c) at T(15), T(90), T(120) and T(end) (P<0.01) and of QT(cd) at T(45) (P<0.05). The mean of QT(d), adjusted for plasma potassium, increased over time in HDF with large alternate mean increase and decrease peaks and error intervals. In HDF(k), instead, there was a progressive and constant diminution with minor error intervals. QT(cd) adjusted for plasma potassium had the same trend. A marked difference was found between the final values in standard HDF and those in HDF(k). HDF and HDF(k) have significantly different effects on QT(c). ECG data demonstrate that the risk of arrhythmia could be lower, with a variable removal of potassium during haemodialysis. With HDF but not HDF(k), hyperpolarization of the cell membrane is detected, and this could have a destabilizing effect on different types of cardiac cell, giving rise to retrograde circuits.

NOT ALL POLYSULFONE (PS) HEMODIALYSIS MEMBRANES (HDM) ARE THE SAME

There are increasing numbers of PS HDM available on the market. However, these membranes have very different structures which may result in measurable differences in their ability to retain bacterial endotoxin (E) We developed an in-vitro method of characterizing the E passage capability of different PS HDM using current E detection methods. Fresenius Optiflux® F200NR (FMC, Lexington, MA) and Gambro Polyflux® 210H (Gambro, Lund, SW) were challenged with a dialysate bath containing approximately 500 EU/ml endotoxin produced from Pseudomonas aeruginosa ATCC 27853 and Stentrophomonas maltophilia ATCC 13637. Detection limits were 0.015 EU/ml using the kinetic turbidimetric LAL method (Charles River Labs). The contaminated dialysate was circulated through the dialysate side of the dialyzers at 500 ml/min. Ultrafiltration of dialysate to the blood side was set at 15 ml/min. Blood side samples were taken at t=0, 7, 15, 60, 67, 75 and 120 minutes. Results: E was not detected in any of the blood side samples for the Fresenius Optiflux® F200 NR while for the Gambro Polyflux® 210H blood side E was detected at 7 minutes and rose to 3 EU/ml at 15 and 60 minutes. High contamination levels of the dialysate was used due to the ability of all membranes to retain some level of endotoxin. The higher contamination values allow for this differentiation and may suggest that even at low E contamination levels during dialysis small quantities of E will cross the membrane and accumulate in the patient. Further in-vivo studies are in progress to quantify these differences and their clinical effects.

Pulse Pressure Determinants in Chronic Hemodialysis Patients

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Hypertension contributes to the high cardiovascular morbidity in patients undergoing chronic hemodialysis therapy (PCHD). Optimal blood pressure (BP) in dialysis patients is not different from recommendations for the general population. The definition of hypertension in patients undergoing chronic hemodialysis therapy is still under debate. Predialysis systolic and diastolic BP is of particular importance. The mean arterial pressure (MAP) also serves as an expression of BP in hemodialysis patients, instead of systolic or diastolic BP. Investigations in the general population have demonstrated the predictive utility of pulse pressure (systolic minus diastolic blood pressure), a measure reflecting the pulsatile nature of the cardiac cycle. Recent recognition of pulse pressure (PP) as an important correlate of mortality in patients receiving dialysis highlights the need to investigate the relationship between PP and clinical outcomes in patients with end-stage renal disease. We conducted this study to demonstrate clinical and biochemical determinants of predialysis and postdialysis PP values during a 15-month period in a group of patients undergoing chronic hemodialysis therapy.

Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation

Background: Activation of polymorphonuclear neutrophils (PMNs) and monocytes has been described during hemodialysis (HD), which results in the release of reactive oxygen species and cytokines. Acetate-free biofiltration (AFB) has been shown to cause less monocyte activation and cytokine release than bicarbonate HD (BHD). No data are available to date on the effect of AFB on PMN activation. Methods: We studied ex vivo superoxide anion release by PMNs isolated from nine patients treated in random order with AFB or BHD (three sessions each). Plasma interleukin-1β (IL-1β) levels and the nitric oxide (NO) synthetic pathway also were evaluated. A polyacrylonitrile (AN69; Hospal, Bologna, Italy) dialyzer was used for both treatments. Fourteen healthy volunteers were used as controls. Blood samples were drawn predialysis and 5 and 15 minutes after starting dialysis to obtain plasma and PMNs. Results: Neither ex vivo superoxide anion release nor blood PMN count was affected by AFB. Conversely, a peak in superoxide anion production associated with a decrease in PMN count was observed at 5 minutes during BHD. Results of superoxide anion production by control PMNs exposed in vitro to AFB or bicarbonate dialysis bath or Hank's balanced salt solution supplemented with bicarbonate or acetate indicated that BHD-induced PMN activation could be attributed to the amount of bicarbonate present in the dialysis bath. IL-1β plasma levels did not change during dialysis with AFB and were numerically higher at 5 and 15 minutes with respect to predialysis values during BHD. Uremic plasma obtained during either AFB or BHD induced greater NO synthesis by human umbilical vein endothelial cells than control plasma. Conclusion: AFB, unlike BHD, does not cause PMN and monocyte activation, which could have a positive impact on dialysis-associated cardiovascular disease of dialyzed patients. © 2002 by the National Kidney Foundation, Inc.

A pharmacokinetic interpretation of increasing concentrations of DEHP in haemodialysed patients

The degree of exposure to DEHP was assessed in 11 patients with chronic renal failure undergoing maintenance haemodialysis. The amount of DEHP leached from the dialyser during a 4-h dialysis session was estimated by monitoring the DEHP blood concentration using a HPLC method. When a patient undergoes a dialysis treatment, the concentration of di-2-ethylhexyl phthalate (DEHP) in venous blood is increased when the blood crosses through the dialysis apparatus. This increase may be explained either because DEHP is not extracted by the dialyser or because DEHP comes from the dialysis bath due to contact of blood against plasticized pipes. To explain the increasing concentration of DEHP during treatment of renal failure using plasticized tubing, we propose a pharmacokinetic compartmental model in order to fit raw data obtained from dialysed patients and to get the amount of DEHP which enters the body by AUC calculations. Results obtained after HPLC analysis show a high degree of interpatient variability in DEHP retained. This amount can reach a toxicity level because of repetitive dialysis treatments over prolonged periods of time. In the coming years, it seems necessary to reconsider the use of DEHP as a plasticizer in medical devices. Highly unacceptable amounts of DEHP leached during the dialysis session could be easily avoided by careful selection of haemodialysis tubing.

Evidence of Hepatitis C Virus Passage Across Dialysis Membrane

The passage of hepatitis C virus (HCV) across the dialysis membrane is a controversial issue. We performed a study applying extreme conditions of permeability to the dialysis membrane and avoiding the use of heparin and dialysis bath that might interfere with polymerase chain reaction (PCR) results. We obtained samples from the ultrafiltrate at the beginning of 18 hemodialysis sessions carried out in 6 HCV RNA-positive patients. HCV RNA was detected by PCR in 3 (16.7%) ultrafiltrate samples belonging to 1 of the patients. HCV genotype was the same as that found in positive ultrafiltrate samples and in the serum corresponding to this patient. The viral load of this patient was under the levels detectable by the assay employed. Therefore, contamination of the ultrafiltrate may constitute a potential risk for HCV transmission in hemodialysis units.

Contribution of dialysis to endogenous oxalate production in patients with chronic renal failure

We tested the possibility that the buffering agents in dialysis bath fluid might contribute to increased endogenous oxalate production in dialyzed patients. Using stable isotope dilution mass spectrometry, we obtained oxalate production rates and pool sizes directly for 10 patients in chronic renal failure, 5 of whom were undergoing continuous ambulatory peritoneal dialysis (lactate-buffered fluid). All peritoneal dialysis patients had either increased oxalate production rates or expanded oxalate pools when compared with undialyzed patients in renal failure. From a further four patients receiving maintenance hemodialysis we took blood samples immediately before and after three consecutive dialysis sessions in which the bath-fluid buffering agent (bicarbonate or acetate) was alternated; we analyzed these samples for oxalate and key precursors by capillary gas chromatography. Plasma glycine and serine concentrations remained within the physiological range. Glycolate and oxalate concentrations decreased, but the oxalate remained above normal after dialysis. All changes were independent of the bath-fluid buffering agent. We suggest that dialysis might stimulate the formation of oxalate by removing product inhibition of a late catabolic step.