I. Ledebo - Academia.edu (original) (raw)
Papers by I. Ledebo
Blood Purification, 1999
The Journal of the American Society of Nephrology recently presented a publication by Henderson, ... more The Journal of the American Society of Nephrology recently presented a publication by Henderson, Colton and Ford from 1975 as a Milestone in Nephrology [1]. The title is ‘Kinetics of hemodiafiltration. II. Clinical characterisation of a new blood cleansing modality’. Rereading this classical paper was like seeing an old photograph of a close friend. All the well-known features are there, although he looks quite different today. Hemofiltration (HF), as the name was later changed to, is characterised by convective solute removal which is independent of molecular weight. Already in the first clinical application [1], the investigators could show increased removal of medium-to-large solutes, reduction of symptoms connected with fluid removal and improved blood pressure control with time, all in comparison with hemodialysis (HD). The importance of the sieving properties of the membrane to allow removal of solutes up to the size of, but not including, albumin was noted. Finally, the authors pointed to what was to become the Achilles’ heel of hemofiltration therapy – the cost and the labor connected with using large volumes of replacement fluid. In the commentaries to this milestone publication, Henderson and Bosch emphasise the great technical contributions to present dialysis therapy that were spin-offs from hemofiltration projects in the late 1970s and 1980s – high-flux membranes, volume control and ultrafiltration to prepare pyrogen-free fluids. These are today essential components of renal replacement therapies, without which we could not perform high-flux dialysis, hemodiafiltration, various forms of CRRT or use ultrapure fluids in hemodialysis. Considering this it may be felt that hemofiltration therapy should be allowed to rest in peace. The epitaph could be that it contributed greatly to present dialysis technology, but did not qualify as a renal replacement therapy. However, there are still nephrologists who are convinced that the clinical benefits of hemofiltration are unequalled by present dialysis therapies, and that many of the clinical problems encountered in today’s dialysis population would be ideally managed by hemofiltration.
Nephrology Dialysis Transplantation, 1998
dialysate containing 37 mmol/l bicarbonate provides Background. Automated peritoneal dialysis (AP... more dialysate containing 37 mmol/l bicarbonate provides Background. Automated peritoneal dialysis (APD) has improved acid-base balance and possibly improved the possibility of increasing the dialysis efficacy by biocompatibility, and may lead to a significant cost using higher fill volumes, frequent dialysate exchanges, reduction. Further development in order to provide and tidal techniques. It is then possible to treat patients smaller machines and more precise ways of achieving adequately without residual renal function. The drawa desired dialysate glucose concentration is necessary. backs of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of Key words: automated peritoneal dialysis; bicarbonate lactate-based dialysate bags and difficulties for the dialysate; on-line-prepared dialysate patients in handling these bags. So far, bicarbonatebased peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' Introduction preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line The number of patients performing automated peritonpreparation of substitution fluid for haemofiltration. eal dialysis (APD) is increasing worldwide [1]. Patients Methods. Four patients without residual renal function often prefer APD during the night because then the were treated with APD five times weekly in a crossday remains free of any manual bag exchange. The over study design. Patients received standard lactateother important reason for the success of APD is the based (35 mmol/l) treatment (25 litres per session frequent necessity to increase efficacy of the standard each) in weeks 1 and 3. In week 2 on-line-produced continuous ambulatory peritoneal dialysis (CAPD) bicarbonate-buffered (37 mmol/l) dialysate was used. with four dialysate exchanges in order to obtain This dialysate was prepared by an AK 100 Ultra adequate dialysis [2-4]. High fill volumes (up to 3.5 haemodialysis machine. The machine was modified for litres), short dwell times (in patients with high peritonadding glucose from a 50% concentrate to the desired eal transport characteristics) and tidal techniques are concentration of 1.7%. Electrolytes, pH, pCO 2 , and also being applied to APD patients to increase the dialysis efficacy parameters were measured. Microdialysis clearance in patients who have lost their residbiological testing was carefully performed. ual renal function [5]. The total amount of dialysate Results. Creatinine clearances, Kt/V, and pCO 2 did necessary per dialysis session then can reach up to 30 not vary between the different treatment phases, litres. The negative consequences as e.g. the difficulty whereas the pH showed a distinct increase during the to handle the multiple 5-litre-dialysate bags and the bicarbonate phase. Repeated determinations of endofact that the cost of treatment becomes even higher toxins and culturing showed no contamination of the than the costs of centre haemodialysis limits the distridialysate. The composition of the produced dialysate bution of APD. was reproducible with respect to pH, pCO 2 , sodium, These drawbacks could only be overcome by the calcium and bicarbonate, whereas the glucose concenon-line preparation of the peritoneal dialysis (PD) tration varied by ±20%. fluids as it has been introduced by Tenckhoff et al. [6 ] Conclusions. On-line preparation of PD fluid with the and used long-term in smaller numbers of IPD patients, AK 100 Ultra is easy and safe to handle. APD with and Quellhorst [personal communication]. However, the opportunity to use advanced technologies, Correspondence and offprint requests to: Prof. Dr R. Brunkhorst, introduced for the on-line preparation of bicarbonate
Kidney International, 2001
Hemodialysis International, 2004
Dialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has ... more Dialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has been considered acceptable because the dialysis membrane was believed to be a protective barrier to blood. However, improved methods for detection of cellular activation have demonstrated that bacterial products in the dialysate may stimulate monocytes to produce cytokines with most dialysis membranes. Ultrapure dialysis fluid is practically free from bacteria and endotoxin (< 0.1 CFU/mL and < 0.03 EU/mL) and can be prepared from standard-quality dialysis fluid using a single step of controlled ultrafiltration. The European guidelines for hemodialysis (HD) set the use of ultrapure dialysis fluid as the goal for all dialysis modalities. Several clinical studies report improved inflammatory status in HD patients when ultrapure dialysis fluid is used, compared with standard-quality dialysate. The benefits include less frequent occurrence of carpal tunnel syndrome, lower C-reactive protein values, reduced need for erythropoietin, better nutritional status, and even better preservation of residual renal function. For patients on daily dialysis, dialysate quality is especially important because such patients are often treated at home where quality control of incoming water may be less rigorous, and increased treatment frequency leads to exposure to larger volumes of dialysis fluid than with conventional dialysis. The use of ultrapure dialysis fluid together with low-complement-activating membranes maximizes the biocompatibility of a dialysis treatment, a goal of treatment, although there is a lack of evidence to date supporting a beneficial effect on mortality. From a physiologic point of view the reduced inflammatory stimulus that can be achieved with ultrapure dialysis fluid is highly desirable. In addition, achieving ultrapure dialysis fluid is realistic, because today it can be practically and economically prepared using modern equipment and applying appropriate microbiologic surveillance techniques.
Blood Purification, 2011
decrease was 15 8 57 g/m 2 during 16 8 7 months. As analyzed by MANOVA (mixed model), the differe... more decrease was 15 8 57 g/m 2 during 16 8 7 months. As analyzed by MANOVA (mixed model), the difference in LVMI over the whole period was statistically significant (p = 0.03) with a more favorable outcome in HF. Blood pressure and other study variables did not differ between the groups, but at baseline and throughout the study, HF patients required heavier antihypertensive treatment. Conclusions: In incident dialysis patients, long-term predilution HF, a purely convective dialysis treatment, is associated with a significantly more favorable development of LVMI compared with regular low-flux HD. Considering the predictive strength of LVMI as a risk factor, the quantitative difference between the treatments is of clinical importance.
Artificial Organs, 1998
There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafi... more There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10-15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and beta2-microglobulin (beta2m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.
Artificial Organs, 1999
With increasing awareness about the degree and the potential impact of microbiological contaminat... more With increasing awareness about the degree and the potential impact of microbiological contamination in dialysis fluids, there is a desire to improve their microbiological quality. To achieve this goal, the origin of the microbiological contamination has to be identified. The water, the bicarbonate concentrate, and the fluid distribution system can be major contributors. Regular disinfection of the entire fluid path is necessary to prevent the formation of biofilm. The bicarbonate concentrate should be handled with special attention because it constitutes an excellent growth medium for microflora that may not be detected with regular assays. With a well maintained reverse osmosis (RO) system, frequent disinfection of the entire flow path, and microbiological awareness, it is possible to produce dialysis fluid that meets the most stringent standard (<10(2) colony forming units (CFU)/ml and <0.25 IU/ml of endotoxin). Adding a step of ultrafiltration just before the dialyzer can make the dialysis fluid ultrapure (<10(-1) CFU/ ml and <0.03 IU/ml). One additional step of controlled ultrafiltration provides sterile and pyrogen-free fluids (<10(-6) CFU/ml and <0.03 IU/ml) that can be used for infusion.
Nephrology Dialysis Transplantation, 2000
Whichever dialysis therapy is used, there is a should be replaced by dialysis in end-stage renal ... more Whichever dialysis therapy is used, there is a should be replaced by dialysis in end-stage renal disease patients. This is achieved by including a buffer in the similar need for correcting the acid-base balance. The dialysis fluid, but the choice of buffer source and mode most important tool for this is the buffer in the dialysis of dialysis are important determinants for the acidfluid and, when using convective therapies, also in the base correction. As acidosis has been shown to affect substitution solution. The buffer source in all modern several metabolic processes in the body, there is general versions of these therapies should be bicarbonate. The agreement that it should be avoided, but the target for more efficient the dialysis treatment in terms of small correction is still subject to discussion. solute transport, the more rapid the uptake of buffer. Thus, optimally applied haemodiafiltration has the potential for the largest buffer gain. The target for Components of acid-base correction in dialysis acid-base correction in dialysis is to maintain patients within or as close to the physiological plasma bicarbon-The buffer gain during a dialysis treatment should be ate range as possible. However, cross-sectional studies sufficient to compensate for the generation of acid of acid-base status among patients treated with conduring the interdialytic period and also for any loss of temporary forms of dialysis often show moderate acidbuffer that takes place during dialysis. The uptake of osis. As metabolic acidosis has been found to be an buffer during dialysis serves not only to increase important stimulus for protein catabolism in experithe plasma bicarbonate level, but also to restore the mental studies, an association with nutritional probbuffering capacity of other body buffer systems. If lems has been sought in dialysis patients. This has the patient has been in positive hydrogen balance, his revealed a negative correlation between plasma bicarnon-bicarbonate buffer stores may have contributed bonate and nutritional parameters. Acidotic patients buffer equivalents and need to be regenerated [1]. This were found to have better nutritional status than can be seen as an extended bicarbonate distribution patients with normalized acid-base balance. However, space [2]. caution should be exercised when interpreting plasma When bicarbonate is used as buffer in the dialysis bicarbonate levels, since acidosis may be a cause as fluid, the uptake is determined by the mass transfer well as an effect of excessive protein catabolism. rate across the membrane. Increasing the efficiency of Although available clinical data suggest that the catadialysis, in terms of small solute clearance, leads to bolic effect of mild acidosis can be compensated by increased rates of transfer of bicarbonate into the adequate nutrition and adequate dialysis, it should be blood. However, it is the difference in concentration desirable to aim for a normalized acid-base balance in between blood and dialysis fluid that makes up the combination with adequate nutritional intake and driving force for the transport and, when the gradient delivery of dialysis. is reduced gradually by rising blood bicarbonate levels, the system approaches a steady state. The titration of Key words: acidosis; bicarbonate; convection; haemonon-bicarbonate buffer stores still proceeds and therediafiltration; haemofiltration fore the treatment time is of importance for the total uptake of buffer. When the buffer source is acetate or lactate, which need to be metabolized before being effective as buffers, the rate of metabolism may be the limiting step and large amounts of bicarbonate may
Peritoneal Dialysis International, 2000
Saudi Journal of Kidney Diseases and Transplantation
... Paolo Altieri 1 , Gianbattista Sorba 2 , Piergiorgio Bolasco 3 , Ingrid Ledebo 4 , Ferruccio ... more ... Paolo Altieri 1 , Gianbattista Sorba 2 , Piergiorgio Bolasco 3 , Ingrid Ledebo 4 , Ferruccio Bolasco 5 , Marino Ganadu 6 , Franco Cadinu 7 , Rocco Ferrara 8 , Gianfranca Cabiddu 1 1 Divisione di Nefrologia e Dialisi, Azienda ... 1. Locatelli F, Del Vecchio L, Manzoni C, et al. ...
The actual dialysis therapy offers a notable long-term survival and rehabilitation, but it is sti... more The actual dialysis therapy offers a notable long-term survival and rehabilitation, but it is still far from normalizing the patient's quality of life as well as mortality and morbidity. The most widely used dialysis therapy is an almost exclusive diffusive treatment performed with low-flux cellulose membranes with a dialysis dose targeted to a urea Kt/V of 1.2 or higher. The convective treatments, which use highflux membranes, offer proven biological superiority over diffusive treatments, which are performed with bio-incompatible, lowflux membranes. Retrospective epidemiological studies have documented a reduction of morbidity and mortality with the use of high-flux membranes, but the results of the prospective studies comparing low-flux with high-flux treatments are still conflicting. Cardiovascular instability during treatment sessions is a potential cause of morbidity and mortality for patients on dialysis treatment. Hemofiltration (HF) is a pure convective treatment an...
Journal of the American Society of Nephrology : JASN, 2002
On-line preparation, i.e., continuous mixing and immediate use, was introduced for dialysis fluid... more On-line preparation, i.e., continuous mixing and immediate use, was introduced for dialysis fluid in 1964, and it contributed significantly to the expansion of dialysis therapy through simplified handling, improved microbiology, and enhanced efficiency. On-line prepared replacement solution for hemofiltration was shown to be clinically safe as early as 1978, but the implementation was delayed for 20 yr because of regulatory conservatism. On-line preparation of sterile and pyrogen-free solutions for infusion is based on the use of water and concentrates that contribute a minimum of microorganisms and are mixed and distributed in a hygienically designed and maintained flow path. Ultrafilters with known retention capacity are placed in strategic positions and dimensioned to remove bacteria and endotoxins, which gives a sterility assurance level of at least six magnitudes, as required by the Pharmacopoeia for sterile products. Microbiologic testing of the fluid should be applied when de...
Advances in renal replacement therapy, 1999
On-line hemodiafiltration (HDF) provides the largest amount of blood purification over a wide mol... more On-line hemodiafiltration (HDF) provides the largest amount of blood purification over a wide molecular weight spectrum achievable with present renal replacement therapies. When used with state of the art dialysis membranes and treatment systems, the biocompatibility of on-line HDF is as high as can presently be defined. From an economic perspective, the added cost of the ultrafilters used to prepare the substitution solution is balanced by the therapeutic benefits of HDF. For optimal HDF, the ultrafiltration rate must be maximized with respect to the blood flow rate. In on-line HDF systems, the excess volume ultrafiltered, approximately 20 to 30 liters per treatment, is automatically replaced, preferably in postdilution mode, by a substitution solution that is continuously generated by stepwise ultrafiltration of dialysate. When properly prepared, this fluid fulfills the quality demands of commercially available infusion solutions; that is, it can be referred to as sterile and pyro...
The International journal of artificial organs, 1995
Postdilution hemofiltration (HF) as practised during the 80's is today associated with limita... more Postdilution hemofiltration (HF) as practised during the 80's is today associated with limitations of a medical, practical and economical nature. High blood flow rates are required to generate sufficient ultrafiltrate in order to achieve a clearance of small solutes comparable to hemodialysis within a reasonable time. High hematocrit and large body weight lead to extended treatment times. IV-quality solution is required in large volumes. This makes the use of bicarbonate difficult and has placed HF among the most expensive renal replacement therapies. These limitations can be resolved by performing HF in a predilution mode using an on-line prepared infusion solution. Diluting the blood before filtration increases the filtration fraction and the clearance of all solutes which are sieved by the membrane. Comparing pre- to postdilution at similar blood flow rates, the clearance may increase by 50% but three times as much infusion solution is required. To make predilution economical...
Contributions to nephrology, 1992
Journal of general microbiology, 1976
The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of ... more The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of these ions to its envelope, has been studied. Bacteria suspended in media of low ionic content showed decreases in wet weight, dry weight and growth capacity, and increases in light scattering and in the release of u.v.-absorbing substances into the medium. The permeability barrier to Ca2+ was also damaged, and there was a release of radioactivity from bacteria labelled with 45Ca2+. These events occurred at the optimum growth temperature, and took place at increased rates at higher temperatures. Damage was prevented to about the same extent by 0.1 mM-CaC12, BaC12 or MgC12 and by 10 mM-NaC1, KC1 or LiC1. Ion competition experiments showed that Ca2+ was preferentially taken up and retained in comparison with Ba2+, Mg2+ and Na+, in that order. Isolated envelopes gave similar results. The dry weight of envelopes was reduced by 35% when they were suspended in water at 40 degrees C. It is clea...
Contributions to Nephrology, 2007
The objective of hemodiafiltration (HDF) is to increase the convective transport of solutes poorl... more The objective of hemodiafiltration (HDF) is to increase the convective transport of solutes poorly removed by diffusion, and therefore ultrafiltration (UF) beyond the desired weight loss is prescribed. The excess UF is compensated for by infusion of a physiological solution which should be sterile and nonpyrogenic. This replacement solution can be provided either in bags containing commercially prepared infusion solution, i.e. so-called classic HDF, or by an integrated stepwise filtration of the dialysis fluid, i.e. so-called online HDF. In both cases the composition of the replacement solution should mirror that of plasma water. When the fluid is provided in bags, practical handling is a limiting factor, and the amount of convection that can be delivered is most often restricted to 10-12 l/session. Results from clinical studies show that the degree of convective transport obtained in classic HDF corresponds to what can be achieved in contemporary high-flux dialysis, where uncontrolled UF and backfiltration take place inside the dialyzer. Classic HDF with replacement fluid in bags offers the possibility of delivering an HDF treatment with controlled convective dose and fluid quality, albeit with a limited amount of convection.
Nephrology Dialysis Transplantation, 1998
Nephrology Dialysis Transplantation, 2006
Blood Purification, 1999
The Journal of the American Society of Nephrology recently presented a publication by Henderson, ... more The Journal of the American Society of Nephrology recently presented a publication by Henderson, Colton and Ford from 1975 as a Milestone in Nephrology [1]. The title is ‘Kinetics of hemodiafiltration. II. Clinical characterisation of a new blood cleansing modality’. Rereading this classical paper was like seeing an old photograph of a close friend. All the well-known features are there, although he looks quite different today. Hemofiltration (HF), as the name was later changed to, is characterised by convective solute removal which is independent of molecular weight. Already in the first clinical application [1], the investigators could show increased removal of medium-to-large solutes, reduction of symptoms connected with fluid removal and improved blood pressure control with time, all in comparison with hemodialysis (HD). The importance of the sieving properties of the membrane to allow removal of solutes up to the size of, but not including, albumin was noted. Finally, the authors pointed to what was to become the Achilles’ heel of hemofiltration therapy – the cost and the labor connected with using large volumes of replacement fluid. In the commentaries to this milestone publication, Henderson and Bosch emphasise the great technical contributions to present dialysis therapy that were spin-offs from hemofiltration projects in the late 1970s and 1980s – high-flux membranes, volume control and ultrafiltration to prepare pyrogen-free fluids. These are today essential components of renal replacement therapies, without which we could not perform high-flux dialysis, hemodiafiltration, various forms of CRRT or use ultrapure fluids in hemodialysis. Considering this it may be felt that hemofiltration therapy should be allowed to rest in peace. The epitaph could be that it contributed greatly to present dialysis technology, but did not qualify as a renal replacement therapy. However, there are still nephrologists who are convinced that the clinical benefits of hemofiltration are unequalled by present dialysis therapies, and that many of the clinical problems encountered in today’s dialysis population would be ideally managed by hemofiltration.
Nephrology Dialysis Transplantation, 1998
dialysate containing 37 mmol/l bicarbonate provides Background. Automated peritoneal dialysis (AP... more dialysate containing 37 mmol/l bicarbonate provides Background. Automated peritoneal dialysis (APD) has improved acid-base balance and possibly improved the possibility of increasing the dialysis efficacy by biocompatibility, and may lead to a significant cost using higher fill volumes, frequent dialysate exchanges, reduction. Further development in order to provide and tidal techniques. It is then possible to treat patients smaller machines and more precise ways of achieving adequately without residual renal function. The drawa desired dialysate glucose concentration is necessary. backs of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of Key words: automated peritoneal dialysis; bicarbonate lactate-based dialysate bags and difficulties for the dialysate; on-line-prepared dialysate patients in handling these bags. So far, bicarbonatebased peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' Introduction preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line The number of patients performing automated peritonpreparation of substitution fluid for haemofiltration. eal dialysis (APD) is increasing worldwide [1]. Patients Methods. Four patients without residual renal function often prefer APD during the night because then the were treated with APD five times weekly in a crossday remains free of any manual bag exchange. The over study design. Patients received standard lactateother important reason for the success of APD is the based (35 mmol/l) treatment (25 litres per session frequent necessity to increase efficacy of the standard each) in weeks 1 and 3. In week 2 on-line-produced continuous ambulatory peritoneal dialysis (CAPD) bicarbonate-buffered (37 mmol/l) dialysate was used. with four dialysate exchanges in order to obtain This dialysate was prepared by an AK 100 Ultra adequate dialysis [2-4]. High fill volumes (up to 3.5 haemodialysis machine. The machine was modified for litres), short dwell times (in patients with high peritonadding glucose from a 50% concentrate to the desired eal transport characteristics) and tidal techniques are concentration of 1.7%. Electrolytes, pH, pCO 2 , and also being applied to APD patients to increase the dialysis efficacy parameters were measured. Microdialysis clearance in patients who have lost their residbiological testing was carefully performed. ual renal function [5]. The total amount of dialysate Results. Creatinine clearances, Kt/V, and pCO 2 did necessary per dialysis session then can reach up to 30 not vary between the different treatment phases, litres. The negative consequences as e.g. the difficulty whereas the pH showed a distinct increase during the to handle the multiple 5-litre-dialysate bags and the bicarbonate phase. Repeated determinations of endofact that the cost of treatment becomes even higher toxins and culturing showed no contamination of the than the costs of centre haemodialysis limits the distridialysate. The composition of the produced dialysate bution of APD. was reproducible with respect to pH, pCO 2 , sodium, These drawbacks could only be overcome by the calcium and bicarbonate, whereas the glucose concenon-line preparation of the peritoneal dialysis (PD) tration varied by ±20%. fluids as it has been introduced by Tenckhoff et al. [6 ] Conclusions. On-line preparation of PD fluid with the and used long-term in smaller numbers of IPD patients, AK 100 Ultra is easy and safe to handle. APD with and Quellhorst [personal communication]. However, the opportunity to use advanced technologies, Correspondence and offprint requests to: Prof. Dr R. Brunkhorst, introduced for the on-line preparation of bicarbonate
Kidney International, 2001
Hemodialysis International, 2004
Dialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has ... more Dialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has been considered acceptable because the dialysis membrane was believed to be a protective barrier to blood. However, improved methods for detection of cellular activation have demonstrated that bacterial products in the dialysate may stimulate monocytes to produce cytokines with most dialysis membranes. Ultrapure dialysis fluid is practically free from bacteria and endotoxin (< 0.1 CFU/mL and < 0.03 EU/mL) and can be prepared from standard-quality dialysis fluid using a single step of controlled ultrafiltration. The European guidelines for hemodialysis (HD) set the use of ultrapure dialysis fluid as the goal for all dialysis modalities. Several clinical studies report improved inflammatory status in HD patients when ultrapure dialysis fluid is used, compared with standard-quality dialysate. The benefits include less frequent occurrence of carpal tunnel syndrome, lower C-reactive protein values, reduced need for erythropoietin, better nutritional status, and even better preservation of residual renal function. For patients on daily dialysis, dialysate quality is especially important because such patients are often treated at home where quality control of incoming water may be less rigorous, and increased treatment frequency leads to exposure to larger volumes of dialysis fluid than with conventional dialysis. The use of ultrapure dialysis fluid together with low-complement-activating membranes maximizes the biocompatibility of a dialysis treatment, a goal of treatment, although there is a lack of evidence to date supporting a beneficial effect on mortality. From a physiologic point of view the reduced inflammatory stimulus that can be achieved with ultrapure dialysis fluid is highly desirable. In addition, achieving ultrapure dialysis fluid is realistic, because today it can be practically and economically prepared using modern equipment and applying appropriate microbiologic surveillance techniques.
Blood Purification, 2011
decrease was 15 8 57 g/m 2 during 16 8 7 months. As analyzed by MANOVA (mixed model), the differe... more decrease was 15 8 57 g/m 2 during 16 8 7 months. As analyzed by MANOVA (mixed model), the difference in LVMI over the whole period was statistically significant (p = 0.03) with a more favorable outcome in HF. Blood pressure and other study variables did not differ between the groups, but at baseline and throughout the study, HF patients required heavier antihypertensive treatment. Conclusions: In incident dialysis patients, long-term predilution HF, a purely convective dialysis treatment, is associated with a significantly more favorable development of LVMI compared with regular low-flux HD. Considering the predictive strength of LVMI as a risk factor, the quantitative difference between the treatments is of clinical importance.
Artificial Organs, 1998
There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafi... more There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10-15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and beta2-microglobulin (beta2m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.
Artificial Organs, 1999
With increasing awareness about the degree and the potential impact of microbiological contaminat... more With increasing awareness about the degree and the potential impact of microbiological contamination in dialysis fluids, there is a desire to improve their microbiological quality. To achieve this goal, the origin of the microbiological contamination has to be identified. The water, the bicarbonate concentrate, and the fluid distribution system can be major contributors. Regular disinfection of the entire fluid path is necessary to prevent the formation of biofilm. The bicarbonate concentrate should be handled with special attention because it constitutes an excellent growth medium for microflora that may not be detected with regular assays. With a well maintained reverse osmosis (RO) system, frequent disinfection of the entire flow path, and microbiological awareness, it is possible to produce dialysis fluid that meets the most stringent standard (<10(2) colony forming units (CFU)/ml and <0.25 IU/ml of endotoxin). Adding a step of ultrafiltration just before the dialyzer can make the dialysis fluid ultrapure (<10(-1) CFU/ ml and <0.03 IU/ml). One additional step of controlled ultrafiltration provides sterile and pyrogen-free fluids (<10(-6) CFU/ml and <0.03 IU/ml) that can be used for infusion.
Nephrology Dialysis Transplantation, 2000
Whichever dialysis therapy is used, there is a should be replaced by dialysis in end-stage renal ... more Whichever dialysis therapy is used, there is a should be replaced by dialysis in end-stage renal disease patients. This is achieved by including a buffer in the similar need for correcting the acid-base balance. The dialysis fluid, but the choice of buffer source and mode most important tool for this is the buffer in the dialysis of dialysis are important determinants for the acidfluid and, when using convective therapies, also in the base correction. As acidosis has been shown to affect substitution solution. The buffer source in all modern several metabolic processes in the body, there is general versions of these therapies should be bicarbonate. The agreement that it should be avoided, but the target for more efficient the dialysis treatment in terms of small correction is still subject to discussion. solute transport, the more rapid the uptake of buffer. Thus, optimally applied haemodiafiltration has the potential for the largest buffer gain. The target for Components of acid-base correction in dialysis acid-base correction in dialysis is to maintain patients within or as close to the physiological plasma bicarbon-The buffer gain during a dialysis treatment should be ate range as possible. However, cross-sectional studies sufficient to compensate for the generation of acid of acid-base status among patients treated with conduring the interdialytic period and also for any loss of temporary forms of dialysis often show moderate acidbuffer that takes place during dialysis. The uptake of osis. As metabolic acidosis has been found to be an buffer during dialysis serves not only to increase important stimulus for protein catabolism in experithe plasma bicarbonate level, but also to restore the mental studies, an association with nutritional probbuffering capacity of other body buffer systems. If lems has been sought in dialysis patients. This has the patient has been in positive hydrogen balance, his revealed a negative correlation between plasma bicarnon-bicarbonate buffer stores may have contributed bonate and nutritional parameters. Acidotic patients buffer equivalents and need to be regenerated [1]. This were found to have better nutritional status than can be seen as an extended bicarbonate distribution patients with normalized acid-base balance. However, space [2]. caution should be exercised when interpreting plasma When bicarbonate is used as buffer in the dialysis bicarbonate levels, since acidosis may be a cause as fluid, the uptake is determined by the mass transfer well as an effect of excessive protein catabolism. rate across the membrane. Increasing the efficiency of Although available clinical data suggest that the catadialysis, in terms of small solute clearance, leads to bolic effect of mild acidosis can be compensated by increased rates of transfer of bicarbonate into the adequate nutrition and adequate dialysis, it should be blood. However, it is the difference in concentration desirable to aim for a normalized acid-base balance in between blood and dialysis fluid that makes up the combination with adequate nutritional intake and driving force for the transport and, when the gradient delivery of dialysis. is reduced gradually by rising blood bicarbonate levels, the system approaches a steady state. The titration of Key words: acidosis; bicarbonate; convection; haemonon-bicarbonate buffer stores still proceeds and therediafiltration; haemofiltration fore the treatment time is of importance for the total uptake of buffer. When the buffer source is acetate or lactate, which need to be metabolized before being effective as buffers, the rate of metabolism may be the limiting step and large amounts of bicarbonate may
Peritoneal Dialysis International, 2000
Saudi Journal of Kidney Diseases and Transplantation
... Paolo Altieri 1 , Gianbattista Sorba 2 , Piergiorgio Bolasco 3 , Ingrid Ledebo 4 , Ferruccio ... more ... Paolo Altieri 1 , Gianbattista Sorba 2 , Piergiorgio Bolasco 3 , Ingrid Ledebo 4 , Ferruccio Bolasco 5 , Marino Ganadu 6 , Franco Cadinu 7 , Rocco Ferrara 8 , Gianfranca Cabiddu 1 1 Divisione di Nefrologia e Dialisi, Azienda ... 1. Locatelli F, Del Vecchio L, Manzoni C, et al. ...
The actual dialysis therapy offers a notable long-term survival and rehabilitation, but it is sti... more The actual dialysis therapy offers a notable long-term survival and rehabilitation, but it is still far from normalizing the patient's quality of life as well as mortality and morbidity. The most widely used dialysis therapy is an almost exclusive diffusive treatment performed with low-flux cellulose membranes with a dialysis dose targeted to a urea Kt/V of 1.2 or higher. The convective treatments, which use highflux membranes, offer proven biological superiority over diffusive treatments, which are performed with bio-incompatible, lowflux membranes. Retrospective epidemiological studies have documented a reduction of morbidity and mortality with the use of high-flux membranes, but the results of the prospective studies comparing low-flux with high-flux treatments are still conflicting. Cardiovascular instability during treatment sessions is a potential cause of morbidity and mortality for patients on dialysis treatment. Hemofiltration (HF) is a pure convective treatment an...
Journal of the American Society of Nephrology : JASN, 2002
On-line preparation, i.e., continuous mixing and immediate use, was introduced for dialysis fluid... more On-line preparation, i.e., continuous mixing and immediate use, was introduced for dialysis fluid in 1964, and it contributed significantly to the expansion of dialysis therapy through simplified handling, improved microbiology, and enhanced efficiency. On-line prepared replacement solution for hemofiltration was shown to be clinically safe as early as 1978, but the implementation was delayed for 20 yr because of regulatory conservatism. On-line preparation of sterile and pyrogen-free solutions for infusion is based on the use of water and concentrates that contribute a minimum of microorganisms and are mixed and distributed in a hygienically designed and maintained flow path. Ultrafilters with known retention capacity are placed in strategic positions and dimensioned to remove bacteria and endotoxins, which gives a sterility assurance level of at least six magnitudes, as required by the Pharmacopoeia for sterile products. Microbiologic testing of the fluid should be applied when de...
Advances in renal replacement therapy, 1999
On-line hemodiafiltration (HDF) provides the largest amount of blood purification over a wide mol... more On-line hemodiafiltration (HDF) provides the largest amount of blood purification over a wide molecular weight spectrum achievable with present renal replacement therapies. When used with state of the art dialysis membranes and treatment systems, the biocompatibility of on-line HDF is as high as can presently be defined. From an economic perspective, the added cost of the ultrafilters used to prepare the substitution solution is balanced by the therapeutic benefits of HDF. For optimal HDF, the ultrafiltration rate must be maximized with respect to the blood flow rate. In on-line HDF systems, the excess volume ultrafiltered, approximately 20 to 30 liters per treatment, is automatically replaced, preferably in postdilution mode, by a substitution solution that is continuously generated by stepwise ultrafiltration of dialysate. When properly prepared, this fluid fulfills the quality demands of commercially available infusion solutions; that is, it can be referred to as sterile and pyro...
The International journal of artificial organs, 1995
Postdilution hemofiltration (HF) as practised during the 80's is today associated with limita... more Postdilution hemofiltration (HF) as practised during the 80's is today associated with limitations of a medical, practical and economical nature. High blood flow rates are required to generate sufficient ultrafiltrate in order to achieve a clearance of small solutes comparable to hemodialysis within a reasonable time. High hematocrit and large body weight lead to extended treatment times. IV-quality solution is required in large volumes. This makes the use of bicarbonate difficult and has placed HF among the most expensive renal replacement therapies. These limitations can be resolved by performing HF in a predilution mode using an on-line prepared infusion solution. Diluting the blood before filtration increases the filtration fraction and the clearance of all solutes which are sieved by the membrane. Comparing pre- to postdilution at similar blood flow rates, the clearance may increase by 50% but three times as much infusion solution is required. To make predilution economical...
Contributions to nephrology, 1992
Journal of general microbiology, 1976
The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of ... more The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of these ions to its envelope, has been studied. Bacteria suspended in media of low ionic content showed decreases in wet weight, dry weight and growth capacity, and increases in light scattering and in the release of u.v.-absorbing substances into the medium. The permeability barrier to Ca2+ was also damaged, and there was a release of radioactivity from bacteria labelled with 45Ca2+. These events occurred at the optimum growth temperature, and took place at increased rates at higher temperatures. Damage was prevented to about the same extent by 0.1 mM-CaC12, BaC12 or MgC12 and by 10 mM-NaC1, KC1 or LiC1. Ion competition experiments showed that Ca2+ was preferentially taken up and retained in comparison with Ba2+, Mg2+ and Na+, in that order. Isolated envelopes gave similar results. The dry weight of envelopes was reduced by 35% when they were suspended in water at 40 degrees C. It is clea...
Contributions to Nephrology, 2007
The objective of hemodiafiltration (HDF) is to increase the convective transport of solutes poorl... more The objective of hemodiafiltration (HDF) is to increase the convective transport of solutes poorly removed by diffusion, and therefore ultrafiltration (UF) beyond the desired weight loss is prescribed. The excess UF is compensated for by infusion of a physiological solution which should be sterile and nonpyrogenic. This replacement solution can be provided either in bags containing commercially prepared infusion solution, i.e. so-called classic HDF, or by an integrated stepwise filtration of the dialysis fluid, i.e. so-called online HDF. In both cases the composition of the replacement solution should mirror that of plasma water. When the fluid is provided in bags, practical handling is a limiting factor, and the amount of convection that can be delivered is most often restricted to 10-12 l/session. Results from clinical studies show that the degree of convective transport obtained in classic HDF corresponds to what can be achieved in contemporary high-flux dialysis, where uncontrolled UF and backfiltration take place inside the dialyzer. Classic HDF with replacement fluid in bags offers the possibility of delivering an HDF treatment with controlled convective dose and fluid quality, albeit with a limited amount of convection.
Nephrology Dialysis Transplantation, 1998
Nephrology Dialysis Transplantation, 2006