Dialysate Buffer Research Articles

Citrate Dialysate with and without Magnesium Supplementation in Hemodiafiltration: A Comparative Study Versus Acetate.

The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one.

#6829 DIFFERENTIAL LIPIDIC PROFILE WITH THE USE OF CITRATE OR ACETATE DIALYSATES

Abstract Background and Aims Unlike other high-cardiovascular-risk populations, the efficacy obtained from lipid-lowering therapy remains uncertain in dialysis-dependent chronic kidney disease (DD-CKD) patients. This is probably given to the exclusion in clinical trials of patients with very high LDL levels, their population's heterogeneity, accompanying cardiovascular morbidities, and the higher mortality risk explained partly by chronic inflammation. The latter has been associated with the accumulation of uremic toxins, membrane biocompatibility, and acetate-based dialysates, which promote inflammation. Different dialysate weak acidifying agents such as lactic, pyruvic, hydrochloric, or citric acids have surged as less-inflammatory alternatives to acetate. This study aims to evaluate the effects of the metabolism of acetate and citrate in the lipidic profile of DD-CKD patients. Method In a unicentric, cross-over, prospective study, we compared the lipidic profile by assessing the plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), high-density (HDL) and very low-density (VLDL) lipoprotein cholesterol, and lipoprotein (a) [Lp(a)] comparing the use of citrate (CD) vs. acetate (AD) as dialysate buffers, after twelve sessions with each one. Prealbumin was also measured to rule out malnutrition as a potential confounding factor. Prevalent (i.e., dialysis vintage ≥3 months) adult patients on maintenance hemodialysis were included. The dialysis prescription parameters and additional medical treatments remained unchanged during their sessions with both dialysates. Quantitative variables are reported with mean and standard deviation. Normal distribution was assessed with the Shapiro-Wilk test, and the comparisons were made with the Student's paired T-test or Wilcoxon's signed-rank test, accordingly. A two-sided p-value ≤0,05 was considered statistically significant. Results After twelve dialysis sessions with CD, compared to AD, there was a statistically significant decline in TG and HDL and an increase in LDL. There was also a notable but non-significant reduction in VLDL (Table 1). Conclusion There were noteworthy differences in the lipid profile that can only be attributed to the change of dialysis fluid, as we avoided inter-individual (with a cross-over design) and intra-individual (different inflammatory or nutritional profiles would not be expected with this short-term setting) variabilities. Further studies must elucidate if the short-term changes induced in the lipidic profile of DD-CKD patients by the dialysate's weak acid translate into clinical implications.

Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism-A Targeted Metabolomics Approach.

Acetate is widely used as a dialysate buffer to avoid the precipitation of bicarbonate salts. However, even at low concentrations that wouldn’t surpass the metabolic capacity of the Krebs tricarboxylic acid (TCA) cycle, other metabolic routes are activated, leading to undesirable clinical consequences by poorly understood mechanisms. This study aims to add information that could biologically explain the clinical improvements found in patients using citrate dialysate. A unicentric, cross-over, prospective targeted metabolomics study was designed to analyze the differences between two dialysates, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Fifteen metabolites were studied to investigate changes induced in the TCA cycle, glycolysis, anaerobic metabolism, ketone bodies, and triglyceride and aminoacidic metabolism. Twenty-one patients completed the study. Citrate increased during the dialysis sessions when CD was used, without surpassing normal values. Other differences found in the next TCA cycle steps showed an increased substrate accumulation when using AD. While lactate decreased, pyruvate remained stable, and ketogenesis was boosted during dialysis. Acetylcarnitine and myo-inositol were reduced during dialysis, while glycerol remained constant. Lastly, glutamate and glutarate decreased due to the inhibition of amino acidic degradation. This study raises new hypotheses that need further investigation to understand better the biochemical processes that dialysis and the different dialysate buffers induce in the patient’s metabolism.

Effect of dialysate bicarbonate and sodium on blood pH in maintenance hemodialysis-A prospective study.

The validity of adjusting dialysate bicarbonate based on pre-hemodialysis (HD) serum bicarbonate is unclear. There are no studies of the impact of dialysate sodium on blood pH. To understand the impact of dialysate bicarbonate and sodium on blood pH. Two hundred arterialized blood samples were obtained on the third session of HD with four configurations of dialysate: sodium (140, 137 mEq/L) and bicarbonate (38, 32 mEq/L). The correlation between pre-HD serum bicarbonate and pH was modest (r=0.6). A lower dialysate sodium (p=0.035) and a higher bicarbonate (p=0.02) associated with a higher post-HD blood pH. The frequency of pre-HD blood pH of <7.4 and a post-HD blood pH of >7.5 did not differ for samples with serum bicarbonate <22, 22-26, or >26 mEq/L. Adjusting dialysate buffer based on pre-HD serum bicarbonate is unnecessary. A higher bicarbonate and lower dialysate sodium associate with post-HD alkalemia.

Choices in hemodialysis therapies: variants, personalized therapy and application of evidence-based medicine.

ABSTRACTThe extent of removal of the uremic toxins in hemodialysis (HD) therapies depends primarily on the dialysis membrane characteristics and the solute transport mechanisms involved. While designation of ‘flux’ of membranes as well toxicity of compounds that need to be targeted for removal remain unresolved issues, the relative role, efficiency and utilization of solute removal principles to optimize HD treatment are better delineated. Through the combination and intensity of diffusive and convective removal forces, levels of concentrations of a broad spectrum of uremic toxins can be lowered significantly and successfully. Extended clinical experience as well as data from several clinical trials attest to the benefits of convection-based HD treatment modalities. However, the mode of delivery of HD can further enhance the effectiveness of therapies. Other than treatment time, frequency and location that offer clinical benefits and increase patient well-being, treatment- and patient-specific criteria may be tailored for the therapy delivered: electrolytic composition, dialysate buffer and concentration and choice of anticoagulating agent are crucial for dialysis tolerance and efficacy. Evidence-based medicine (EBM) relies on three tenets, i.e. clinical expertise (i.e. doctor), patient-centered values (i.e. patient) and relevant scientific evidence (i.e. science), that have deviated from their initial aim and summarized to scientific evidence, leading to tyranny of randomized controlled trials. One must recognize that practice patterns as shown by Dialysis Outcomes and Practice Patterns Study and personalization of HD care are the main driving force for improving outcomes. Based on a combination of the three pillars of EBM, and particularly on bedside patient–clinician interaction, we summarize what we have learned over the last 6 decades in terms of best practices to improve outcomes in HD patients. Management of initiation of dialysis, vascular access, preservation of kidney function, selection of biocompatible dialysers and use of dialysis fluids of high microbiological purity to restrict inflammation are just some of the approaches where clinical experience is vital in the absence of definitive scientific evidence. Further, HD adequacy needs to be considered as a broad and multitarget approach covering not just the dose of dialysis provided, but meeting individual patient needs (e.g. fluid volume, acid–base, blood pressure, bone disease metabolism control) through regular assessment—and adjustment—of a series of indicators of treatment efficiency. Finally, in whichever way new technologies (i.e. artificial intelligence, connected health) are embraced in the future to improve the delivery of dialysis, the human dimension of the patient–doctor interaction is irreplaceable. Kidney medicine should remain ‘an art’ and will never be just ‘a science’.

MO795CALCIUM BALANCE AND CKD-MBD PARAMETERS DIFFERENCES OF CITRATE VS. ACETATE DIALYSATE

Abstract Background and Aims Dialysate composition is an essential feature of hemodialysis treatment. The use of acetate as the dialysate buffer and its calcium concentration are still topics of debate. Calcium transfer during dialysis sessions is related to short-term (hemodynamic tolerance and arrhythmias) and long-term effects (cardiovascular calcification and mortality). This study aims to identify the potential benefits derived from acetate-free dialysis by using citrate as a buffer in terms of calcium balance and CKD-MBD biomarkers. Method We performed a prospective crossover study that analyzed 24 dialysis sessions, 12 with each dialysate buffer, on every patient. Ionized calcium and CKD-MBD parameters were analyzed with each acidifier. Both dialysates had a calcium concentration of 1.5 mml/L. The remaining hemodialysis patients’ parameters were unchanged during the study period. Results No differences were found between pre-dialytical ionized calcium (iCa) (1,11 ± 0,12 vs. 1,08 ± 0,12 mmol/L) in both groups. However, we identified a significant iCa increase in the sessions were acetate dialysate was used, both in immediate (1,29 ± 0,07 mmol/L) and in 30-minutes post-dialytical blood analysis (1,22 ± 0,07 mmol/L). Whereas iCa levels remained stable during the immediate (1,07 ± 0,06 mmol/L) and 30-minutes post-dialytical analysis (1,08 ± 0,11 mmol/L) when using citrate. On the other hand, pre-dialysis albumin-corrected total calcium was higher with acetate (8,9 ± 0,6 vs. 8,31 ± 0,75 mg/dL, p = 0,003) and PTH was lower with acetate (169 vs. 267 pg/mL, p &amp;lt; 0,001). Conclusion Acetate-free dialysis using citrate as an acidifier stabilizes iCa levels during dialysis sessions while maintaining a neutral or negative effect in calcium balance. This analytical benefit may translate into better cardiovascular long-term outcomes.

Improvements in Inflammation and Calcium Balance of Citrate versus Acetate as Dialysate Buffer in Maintenance Hemodialysis: A Unicentric, Cross-Over, Prospective Study

Introduction: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. Methods: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients’ treatment remained unchanged during the study period. Results: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. Conclusions: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes.

Optimizing serum total carbon dioxide concentration during short and nocturnal frequent hemodialysis using lactate as dialysate buffer base.

Definitive clinical studies to determine the optimal dialysate lactate concentration to prescribe during frequent hemodialysis when using the NxStage System One dialysis delivery system at low dialysate flow rates have not been reported. We used clinical data from patients who transferred from in-center thrice-weekly hemodialysis (ICHD) to daily home hemodialysis using the NxStage System One and the H+ mobilization model to calculate acid generation rates in patient sub-groups during the FREEDOM study. Assuming those acid generation rates were representative, we then predicted using the H+ mobilization model the effect of using dialysate lactate concentrations of 40 and 45 mEq/L on predialysis serum total carbon dioxide (tCO2 ) concentrations in patients who transfer from ICHD to short and nocturnal frequent hemodialysis prescriptions used in current clinical practice; the prescriptions evaluated varied by treatment frequency, dialysate volume per treatment, and treatment times. With frequencies of four to six treatments per week and treatment times of 170 to 210 minutes per treatment, the effect of dialysate lactate concentration was primarily dependent on weekly dialysate volume. For weekly dialysate volumes of 150 to 160 L per week, use of dialysate lactate concentrations of 45 mEq/L, but not 40 mEq/L, resulted in an increase of predialysis serum tCO2 concentration. When longer treatment times typical of nocturnal frequent hemodialysis were evaluated, model predictions showed that the use of dialysate lactate concentration of 45 mEq/L may not be appropriate for many patients because of excessive increases in predialysis serum tCO2 concentration. Reducing dialysate volume from 60 to 30 L may limit the increase in predialysis serum tCO2 concentration when patients transfer from ICHD to nocturnal frequent hemodialysis. Predictions from the H+ mobilization model show that dialysate lactate concentration and weekly dialysate volume are the primary prescription parameters for optimizing predialysis serum tCO2 concentration during short and nocturnal frequent hemodialysis.

Acid-base kinetics during hemodialysis using bicarbonate and lactate as dialysate buffer bases based on the H+ mobilization model.

The H+ mobilization model has been recently reported to accurately describe intradialytic kinetics of plasma bicarbonate concentration; however, the ability of this model to predict changing bicarbonate kinetics after altering the hemodialysis treatment prescription is unclear. We considered the H+ mobilization model as a pseudo-one-compartment model and showed theoretically that it can be used to determine the acid generation (or production) rate for hemodialysis patients at steady state. It was then demonstrated how changes in predialytic, intradialytic, and immediate postdialytic plasma bicarbonate (or total carbon dioxide) concentrations can be calculated after altering the hemodialysis treatment prescription. Example calculations showed that the H+ mobilization model when considered as a pseudo-one-compartment model predicted increases or decreases in plasma total carbon dioxide concentrations throughout the entire treatment when the dialysate bicarbonate concentration is increased or decreased, respectively, during conventional thrice weekly hemodialysis treatments. It was further shown that this model allowed prediction of the change in plasma total carbon dioxide concentration after transfer of patients from conventional thrice weekly to daily hemodialysis using both bicarbonate and lactate as dialysate buffer bases. The H+ mobilization model can predict changes in plasma bicarbonate or total carbon dioxide concentration during hemodialysis after altering the hemodialysis treatment prescription.

Renal Association Clinical Practice Guideline on Haemodialysis

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: “what does good quality haemodialysis look like?”The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to – most of this is freely available online, at least in summary form.A few notes on the individual sections:This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines “enough” dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term “eKt/V” is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient.This section deals with “non-standard” dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week – this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here.This section deals with membranes (the type of “filter” used in the dialysis machine) and “HDF” (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it’s as good as but not better than regular dialysis.This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this.This section deals with dialysate, which is the fluid used to “pull” toxins out of the blood (it is sometimes called the “bath”). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate.This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects.This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful.This section draws together a few aspects of dialysis which don’t easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered.There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.

New chemistry supporting portable solutions for end-stage renal disease dialysis treatment

A new polymeric adsorbent to improve portable dialysis treatment by simplifying urea removal at the dialysate regeneration step is proposed. An adsorbent to remove urea was synthesized by molecular imprinting technology that can potentially overcome drawbacks existing in urease enzyme-based dialysate regeneration technology. Molecularly imprinted polymer (MIP) for urea generates cavities both in shape and in size targeted for urea. Using the synthesized MIP, we have shown removal of urea present in the dialysate buffer. Various experimental conditions such as choice of monomers, porogen, and template to monomer ratios were optimized to achieve highest binding capacity on a column flow through system monitored using high-performance liquid chromatography (HPLC). Taking advantage of the basicity of urea molecule, monomers having Brønsted acidic groups such as acrylic acid, methacrylic acid and itaconic acid were screened. The MIP synthesized using urea:acrylic acid:EGDMA (1:4:12) in acetonitrile:ethylene dichloride (1:1) as porogen gave highest binding capacity of 24.5g/kg of urea in the dialysate buffer matrix.

Nouveaux dialysats : quel acide dans le bain de dialyse ?

The mix of bicarbonate and divalent cations requires a small amount of acid to avoid insoluble precipitation in the dialysate buffer. Small doses of acetic acid (3–7mmol/L) are commonly used. Acetic acid may be replaced by hydrochloric acid or citric acid to achieve acetate-free haemodialysis. Hydrochloric acid theoretically avoids metabolic side effects of acetate. However, additional cost generated by technical constraints probably slowed its generalization. Citric acid has been proposed as a more biocompatible acidifier than acetic acid. By binding calcium, citric acid inhibits both coagulation and complement activation and may reduce the treatment-induced inflammatory response. However, results of the study are conflicting, especially regarding impact on calcium and phosphate metabolism and acid-base metabolism. On the basis of current findings, systematic replacement of acetic acid by citric acid cannot be proposed for all the patients.

Microbiological monitoring of ultrapure dialysis fluid in a hemodialysis center in Alexandria, Egypt

Microbiological contamination of dialysate is an issue that attracted attention since the 1990s. This is partly due to the extensive use of sodium bicarbonate as a dialysate buffer, which helps mic...

Acid base status of prevalent peritoneal dialysis patients

Acid-base status of patients on peritoneal dialysis is influenced by multiple factors. Metabolic acidosis is a common feature of chronic renal failure and dialysis treatment provides alkali in the dialysate in order to maintain a normal acid-base balance. This paper reports the prevalence of acid-base disorders in peritoneal dialysis patients and their associations with clinical and laboratory parameters. This is a cross-sectional retrospective study that included all PD patients registered in the RDPLF database. Metabolic acidosis was found in 20.4% of patients while 27.8% of patients had metabolic alkalosis. There is a significant relationship between age, protein intake estimated by nPNA and the level of alkaline reserve pleading in favor of the influence of dietary intakes in the maintenance of metabolic acidosis. Low residual renal function is associated with a lower probability of being in metabolic alkalosis. These results could allow an individual choice of the dialysate buffer in order to permanently obtain stable acid-base status in patients on peritoneal dialysis.

Basics of base in hemodialysis solution: Dialysate buffer production, delivery and decontamination.

Hemodialysis requires the use of high volumes of freshly prepared, clean dialysate to foster the removal of low molecular weight metabolites (i.e., urea) and to correct the electrolyte and acid-base imbalance of chronic renal failure. Dialysate is produced by mixing clean, AAMI grade water with both an acid and base concentrate. This purpose of this report is to describe production, mixing and delivery of the buffer component of dialysate, and to also to address the cost, safety and feasibility of producing online bicarbonate. As endotoxin contaminated dialysate has been associated with the release of key mediators in acute and chronic inflammatory diseases associated with long-term hemodialysis therapy, aspects of disinfecting a bicarbonate delivery loop are also addressed.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

Management of Sepsis-Induced Acute Kidney Injury

Acute kidney injury (AKI) occurs in a significant proportion of patients with severe sepsis, and is an important cause of mortality in such patients. Current concepts of pathogenesis of AKI are shifting from vasoconstriction-ischaemia induced injury to toxic and immune mediated injury and hyperaemic injury resulting in apoptosis of renal cells. Renal replacement therapy is the mainstay of management of AKI. Adequacy of dialysis is likely to be linked to better outcome, but there is still no clear consensus on the timing, modality, intensity or frequency of dialysis. Haemodynamically unstable patients usually require modes of continuous renal replacement therapy. Biocompatible dialyser membranes are likely to be safer than older cellulose membranes. Bicarbonate is preferred to acetate and lactate as dialysate buffer. Anticoagulation has to be undertaken with care to prevent excessive haemorrhage in the setting of already deranged haemostasis. Adequate volume resuscitation and maintenance of renal perfusion by the use of vasopressors is beneficial; norepinephrine is the vasopressor of choice. There is no place for the use of low- or renal-dose dopamine, mannitol or frusemide in the setting of sepsis-induced AKI, and in fact they may be detrimental. Prevention of kidney damage by nephrotoxic drugs and radio-contrast media is of vital importance. Careful dose management of nephrotoxic drugs will prevent renal injury. Hydration prior to administration of contrast media prevents nephrotoxicity, but the benefit of N-Acetylcysteine is unclear. Tight glycaemic control may have renoprotective effects, though its place in the management of severe sepsis is now controversial. No clear evidence of benefit is seen with other newer therapies.Keywords: Critical care; acute kidney injury; dialysis; renal replacementCitation: Rajapakse S, Rodrigo C, Wijewickrema ES. Management of Sepsis-Induced Acute Kidney Injury. Sri Lanka Journal of Critical Care 2009;1:3-14DOI: 10.4038/sljcc.v1i1.937

The impact of haemodialysis-associated variables on lipid profile in Egyptian haemodialysis population

Haemodialysis (HD) patients appear to have particular susceptibility for cardiovascular (CV) diseases with lipid abnormalities among its significant contributors. However, there is controversy concerning the combined effect on lipid constituents during HD of the three commonly used variables; the type of heparin, dialysis membrane and the constituent of dialysate buffer bases. Consequently, this controlled prospective study was thought of. Randomly 63 patients were assigned from Urology and Nephrology haemodialysis (HD) unit, Mansoura, Egypt for the planned study. Their mean age was 45.79 +/- 13.11 years. Fourteen patients with end-stage renal disease (ESRD) served as control group for the remaining 49 HD patients. They were subdivided according to the HD duration (< and > 1 year), anticoagulant used (unfractionated [UFH] and low-molecular weight heparin [LMWH, Enoxaparin), membrane type (Hemophane [HP] and polysulfone [PS] membrane) and dialysate buffer bases (bicarbonate versus acetate based). Determining the fasting lipid value of total cholesterol (TC) and triglycerides (TG) as well as lipoproteins including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and lipoprotein (a) [Lp (a)] was completed. Bicarbonate dialysate was associated with significantly lower TG (134.7 +/- 11 mg/dl vs. 153 +/- 14 mg/dl, p = 0.004), higher HDL-C (33.1 +/- 3 vs. 28.3 +/- 2, p = 0.0002) and subsequently better atherosclerosis risk ratio [TC/HDL-C (ARR)] (6.02 +/- 0.09 vs. 5.3 +/- 0.9, p = 0.001) despite its insignificant effect on TC and LDL-C. However, logarithm (log) Lp (a) level was significantly higher (1.92 +/- 0.05 vs. 1.82 +/- 0.04 p = 0.001) in comparison with acetate dialysate. Membrane type was not influential in those dialyzed for < 1 year before intervention while after a year of HD, PS (n = 11) compared to HP filters (n = 11) significantly lowered TC (151.7 +/- 16 vs. 172.6 +/- 12, p = 0.003), TG (127.8 +/- 15 vs. 155.7 +/- 15, p = 0.004), LDL-C (122.1 +/- 5 vs. 130.6 +/- 7, p = 0.006) levels as well as ARR (5.9 +/- 0.5 vs. 5.4 +/- 0.3, p = 0.02). Likewise was the reduction in log Lp (a) (1.9 +/- 0.03 vs. 1.8 +/- 0.04, p = 0.002) with insignificant effect on HDL-C. After 6 months, Enoxaparin caused significant improvement of TC (0.0004), TG (p = 0.018), LDL-C (p = 0.006), HDL-C (0.041) and Lp (a) (0.047) compared to UFH. Patients who continued on Enoxaparin for 3 more months displayed an even better attenuation in most of lipid parameters whilst continuation of UFH was insignificant. Switching few patients (n = 4) from UFH to LMWH for 3 months resulted in significant lowering of TC (153 +/- 7 vs. 177.7 +/- 3, p = 0.01), TG (127.5 +/- 5 vs. 137.3 +/- 4, p = 0.03) and LDL-C (124.7 +/- 5 vs. 127.5 +/- 5, p = 0.005). However, switching equal number of patients from LMWH to UFH caused no significant change. Dyslipidaemia in Egyptian haemodialysis patients was improved when bicarbonate-based haemodialysis, the use of polysulfone membrane, and more so when the low-molecular weight heparin Enoxaparin were used.

Challenges and future of renal replacement therapy

Renal community increasingly recognizes the challenges of very high mortality, morbidity and low quality of life among dialysis patients. Current hemodialysis (HD) schedule provides less than 10% of the clearance power of the natural kidneys and therefore current standard HD treatment is still a long way from providing adequate renal replacement. In the future it would be expected to improve dialysis control with the development of new technology: membranes, dialysate buffer, electrolyte concentration, system interface, arteriovenous access monitoring. Online technology must be adapted to routine HD for new prescription monitoring such as creatinine online sensing technology, sodium-specific electrode or hydrogen ion concentration. Online convective therapies offer the opportunity for a more biological renal replacement therapy increasing convective transport in order to "reproduce" glomerular function and improving small and middle molecular clearance in an economically feasible and safe way. The paradigm of thrice-weekly dialysis is faced with diminishing returns, with the possible exception of long dialysis sessions. More frequent (daily) dialysis represents a very promising tool for improving dialysis outcomes and quality of life. Future technologies for renal replacement include bioartificial kidneys based in continuous hemofiltration and bioartificial tubules. Although Phase I/II clinical trial on 10 patients with acute renal failure has been reported the procedure requires further evaluation. Organogenesis, therapeutic cloning, or cloning and organogenesis combined might in the future produce a functional and histocompatible kidney. The continuous increase in incidence and prevalence of renal-replacement therapy is a world-wide phenomenon, although the rates in Europe are still much lower than in the U.S. The increase in rates applies especially to older patients, patients with diabetes mellitus and renal vascular disease and the consequences of this important comorbidity are very important in terms of mortality.

The efficiency of potassium removal during bicarbonate hemodialysis

Patients on chronic hemodialysis often portray high serum [K+]. Although dietary excesses are evident in many cases, in others, the cause of hyperkalemia cannot be identified. In such cases, hyperkalemia could result from decreased potassium removal during dialysis. This situation could occur if alkalinization of body fluids during dialysis would drive potassium into the cell, thus decreasing the potassium gradient across the dialysis membrane. In 35 chronic hemodialysis patients, we compared two dialysis sessions performed 7 days apart. Bicarbonate or acetate as dialysate buffers were randomly assigned for the first dialysis. The buffer was switched for the second dialysis. Serum [K+], [HCO3-], and pH were measured in samples drawn before dialysis; 60, 120, 180, and 240 min into dialysis; and 60 and 90 min after dialysis. The potassium removed was measured in the dialysate. During the first 2 hr, serum [K+] decreased equally with both types of dialysates but declined more during the last 2 hr with bicarbonate dialysis. After dialysis, the serum [K+] rebounded higher with bicarbonate bringing the serum [K+] up to par with acetate. The lower serum [K+] through the second half of bicarbonate dialysis did not impair potassium removal (295.9 +/- 9.6 mmol with bicarbonate and 299.0 +/- 14.4 mmol with acetate). The measured serum K+ concentrations correlated with serum [HCO3-] and blood pH during bicarbonate dialysis but not during acetate dialysis. Alkalinization induced by bicarbonate administration may cause redistribution of K during bicarbonate dialysis but this does not impair its removal. The more marked lowering of potassium during bicarbonate dialysis occurs late in dialysis, when exchange is negligible because of a low gradient.