High Cut-Off Extended Dialysis - Term Paper Example

Name : Tutor : Title : Institution : Date : @ 2012 LITERATURE REVIEW Introduction Renal failure is a cause of many cases of mortality and morbidity. It is a dangerous condition that is treated through the removal of free light chains through haemodialysis (Hutchison, Cockwell, Reid, Chandler, Mead, Harrison, Hattersley, Evans, Chappell, Cook, Goehl, Storr, Bradwell 2007, 890). Many authors have written about extended haemodialysis using high cut off dialysis to remove free light chains in patients having acute renal failure secondary to multiple myeloma. Extended haemodialysis is the most effective, most credible and the most superior method of dealing with free light chains and consequently renal failure. It is used by many health practitioners sometimes in combination with other methods. It has shown tremendous development and success over time and therefore deserves to be studied. This paper presents a review of some of the journal articles published on this topic. The scope of the review is restricted to journal articles. There are many studies that have been done on other methods of removal of free light chains from the blood. However, because this review is on haemodialysis as a method of FLC removal it will not expand to cover the other methods. The review has the introduction, the body which includes the literature development through the years, discussion of the findings, summary and analysis of reviewed literature and finally the conclusion. Extended haemodialysis by use of high cut off dialyzer has the capacity to remove many free light chains when used on patients having acute renal failure secondary to multiple myeloma. Free light chains result from intact l g synthesis and their removal from circulation is accomplished through renal clearance (Zucchelli, Pasquali, Cagnoli, Ferrari 1988, 1177). With the recovery of the renal function, the outcome of the patient is bound to improve. Several studies done on this topic have come out with contradicting results while some of them tend to agree on some aspects and not others. Development of literature over time Literature on extended haemodialysis to remove free light chains has been developing over time. This has been going on as the process of haemodialysis developed from discovery through the stages to its present level. Some authors have documented studies with the use of the newly discovered process and equipment (Bostrom, Freedman 2010, 1110). Other authors have documented results on the improved extended dialysis process and the improved dialyzer. Important improvements on the dialyzer and other equipment for haemodialysis took place during the 1940s and 1950s. Literature has been changing as researchers made efforts to improve the equipment. For example Nils Alwal was the one who began the application of hydrostatic pressure in ultrafiltration. During this time, most of the literature developed was based on experiments on the use of hydrostatic pressure to achieve ultrafiltration and the entire new system. Before they could agree on the superiority of the dialyzer author studies were focused on other methods of removal for free light chains (Torra, Blade, Cases, Lopez-Pedret, Montserrat, Rozman, Revert 1995, 1856). With the coming of the coil and later the twin dialyzer, many studies were done on these new equipment and their use in haemodialysis. A totally new phase in haemodialysis came in 1960 when the Quinton and Scribner AV shunt were introduced. Studies at that time were about the suitability of these discoveris in haemodialysis. Many studies were designed to get better ways of use for effective haemodialysis. Many studies done during this time involved the use of silastic tubes with Teflon tips fitted on them and the radial artery was the target as well as the cephalic vein. This method was applied in many studies because it introduced a new thing. Blood in the patient could circulate continuously, even when the machine was disconnected. This could help avoid clotting and through it repeated haemodialysis could be done over a long time (Rayner, Haynes, Thompson, Russell, Fletcher 1991, 520) Another important development featured in studies on haemodialysis happened when Brescia and Crimino came up with an arterio-venous fistula to be used in chronic vascular access. This created a point of interest for many researchers and many articles were written on this. In the last forty years studies have focused on the design of the dialyzer, biocompatibility of the membrane, hermofiltration and hemodiafiltration among other things that concern extended haemodialysis (Pozzi, Pasquali, Donini, Casanova, Banfi, Tiraboschi, Furci, Porri, Ravelli, Lupo 1987, 5). Discussion of findings From the articles reviewed, different authors have presented the procedures they used and the findings they got form their studies. At the beginning when patients present themselves, about 50% of them present with renal impairment and up to 20 percent show up with acute renal failure (Nozza, Siracusano, Armando 2006, 970). A review done on a large registry in Europe, demonstrated that renal morbidity is a huge burden. Although reversible factors like hypercalcaemia, dehydration and medical treatment are to blame, monoclonal free light chains cause the biggest percentage of renal failure (Magee et al 1999, 604). Huge quantities of free light chains go through the glomerular fenestrations and overpower the ability of the proximal tubules to absorb. When they enter the distal tubules they precipitate with other substances to form some waxy substances that prevent urine from flowing and result in interstitial inflammation. A study by Montseny, Kleinknecht, Meyrier, Vanhille, Simon, Pruna, Eladari (1998, 1440) has analyzed the rates of renal recovery following the removal of free light chains by haemodialysis. Results obtained from these studies have however not been pleasing. Although the study produced an early report that was promising, there was no clinical benefit obtained from the subsequent bigger trials. The study failed because the concentrations of free light chains in urine and serum were not monitored. This is a problem that has been identified in a few other studies where researchers tend to leave out certain important procedures. The end result is that the outcome of the study is either misleading or not credible at all. In a study done by Magee, Vella, Tormey, Walshe (1998, 601) on two cases with acute renal failure, extended high cut off haemodialysis was found to be a substitute process for plasma exchange for the removal of free light chains. The process has shown a rate of clearance of these free light chains of 30 to 40 ml per minute for lambda and kappa free light chains. With this, the concentrations of serum reduced by 60 to 70% for each session. When the sera belonging to patients from whom removal of free light chains using extended HCO-HD was evaluated, it showed that the available free light chains were below the cut off molecular weight of the high cut off membrane. In the two cases studied by Magee, Vella, Tormey, Walshe (1998, 601), free light chains were not removed using extended HCO-HD. Even though many authors have agreed on the fact that extended high cut off haemodialysis has the ability to remove free flight chains and therefore cure renal failure, there is a point of agreement as well. Some studied done by certain authors show that the removal of free light chains can be impossible. This would happen where the polymers are weighty. The study done by Magee et al (1998, 601) is a classic example. In the two cases studied, size exclusion chromatography showed that huge polymers existed. Because the large molecular weight found in the polymers was more that the cut off for the dialyzer and in the process this limited the removal process. The clinical utility of the method of extended hemodialysis by use of high cut off dialysis (HCO-HD) where free light chains in people with multiple myeloma is yet to be known. For this reason, it has become a point of disagreement between authors (Katzung, Bertram 2007, 733).  Renal failure results in a lot of mortality and morbidity cases. Kyle, Gertz, Witzig, Lust, Lacy, Dispenzieri, Fronseca, Rajkumar, Offord, Larson, Plevak, Therneau, Greipp (2003, 26) found that the concentrations of serum in monoclonal free light chains could be excess by many thousands times over the ordinary in people with multiple renal failure secondary to multiple myeloma. With reversible factors not included, it has been observed through many studies that renal failure in most of the patients is cast nephropathy. This is a result of high concentrations of free light chains in serum. Because of this, many experiments have been done to reduce the concentrations of free light chains in serum. A study done by Knudsen, Hjorth, Hippe (2000, 177) showed that people with cast nephropathy could recover from renal failure when the free light chains in serum went down by over 50%. For this reduction to be obtained, studies done earlier recommended the use of chemotherapy which reduces the rate of production of free light chains from the plasma cell clone. Removing the free light chains from serum could serve as adjuvant treatment. In the past, plasma exchange was used for removing these free light chains (FLCs). However, the outcome of the best clinical experiments has not indicated any achievement. Analyzing the FLCs of serum makes it possible for results to be obtained and reported on the same day. This enables clinicians to know those patients with a problem of removal of free light chains using high cut off haemodialysis (Winearls 1995). A study carried out by Johnson, Kyle, Pineda, O'Brien, Holley (1990, 865) sought to find out the possibility of totally removing free light chains through haemodialysis. From the in vitro experiments they did they discovered that they could use many different dialyzers. The main method of clearance was membrane binding. Other results from in vivo and in vitro dialysis indicated that the Gambro 1100 dialyzer having a cut off of 45 kD had the highest efficiency. The researchers concluded that every day extended dialysis by use of Gambro HCO 1100 dialyzer has the capacity to continuously get rid of huge amounts of free light chains. They found out that through clinical and modeling results that removal of FLCs was through haemodialysis was more fruitful than when plasma exchange procedures are used. Support for this can be found in clinical efficacy since renal recovery was good in majority of the patients having cast nephropathy. There is need for more studies in patients where optimal chemotherapy will be given a chance as well as infection control. This could necessitate controlled hemodialysis trials by use of Gambro HCO dialyzers to establish the general clinical utility. Another study done by Irish, Winearls, Littlewood (1997, 775) was aimed at creating a model for removing free light chains in order to understand the different strategies of treatment available. With available variables for the model and data of patients the researchers modeled successfully free light chain removal in vivo. With this it was possible for them to calculate the rates of removal for free light chains between the compartments outside and within the blood vessels. It also made comparison between plasma exchange and hemodialysis an easy task. It was clear from the model that given between 8 to 12 hours of dialysis on daily basis there was a possibility that there would be a reduction in the free light chains to very low concentrations in the serum in only a few days as long as chemotherapy did not fail. In a different study on haemodialysis use for removal of FLCs, a number of tumor killing rates were applied within the model designed in the study. The tumor killing rates were used so that various clinical possibilities could be afforded. Since tumor killing was not done very efficiently, the ongoing production of free light chains made haemodialysis to be more effective in comparison to plasma exchange methods. Summary and analysis of literature For some of the theoretical models developed in certain studies for use in free light chain removal and reviewed in this paper, there is need for more assessment to ascertain their accuracy and mode of reproducibility. Modeling renal free light chain metabolism may be a difficult task since it alters in the process of recovery. The models developed so far however have made it possible for researchers to compare various regimens of treatment. Those models in which tumor killing rates were used were disadvantageous because presently there may be no published reports about tumor killing rates that can be used for purposes of comparison. Many authors tend to agree on the fact that renal failure is treatable with the removal of the free light chains through haemodialysis. However the methodologies of removal of these chains differ with some researchers preferring those that other researchers tend to dislike. Formerly, many authors agreed on the use of plasma exchange for removing free light chains. With new studies being done on hemodialysis as a new method there are varying opinions on its suitability and effectiveness. A number of methods have been employed by researchers in their studies. Some researchers subject patients to sessions of haemodialysis for around 8 hours with a HCO-HD filter in use. In this method the researchers would measure the levels of light chains in serum are measured with a nephelometry. This necessitates the recording of other parameters. Together with nephelometry patients are required to undergo chemotherapy. This method of combining haemodialysis with chemotherapy has been found to be highly effective. However it presents its own problems especially where the procedures for the two choices have to be harmonized. Renal failure is successfully treated through the reduction of FLCs within the blood. Reducing the free light chains in the blood can be achieved through plasmapheresis. However the efficacy of this method is yet to be proven clearly. In order to stop irreversible renal damage by the free light chains there is need to use a chemotherapeutic regimen that can help stop their production. This is done as a method of removal is put in place. Some authors such as Cserti, Haspel, Stowell, Dzik (2007, 513) advocate for plasmapheresis for removing the free light chains in people with acute kidney injury. Recent studies however have failed to show the advantage of plasmapheresis when compared to chemotherapy to help patients recover from the dialysis process. The most popular method today for the removal of FLCs is extended haemodialysis that uses a filter with a big pore that is peameable to proteins. The filter used here has a cut off of 50kDa and this makes it possible for the removal of both lambda and kappa. Extended dialysis is by far effective than plasmapheresis when it comes to removing FLCs. This success can be attributed to the long time used which goes up to 8 hours (Knudsen, Hjorth, Hippe 2000, 177). Reduction of the free light chains using HCO-HD cannot be enough and therefore treatment is necessary to get rid of the FLCs. Heyne, Weisel, Hutchison, Friedrich, Goehl, Kanz, Risler 2007, 124) recommend from their studies that bortezomib be used as a treatment to reduce the free light chains. In this case the use of HOD-HD went on for too long to bring down the FLC load and keep it down. The use of HOD-HD however requires the availability of resources although this can be countered by the fact that patients are not subjected to haemodialysis forever (Ludwig, Drach, Graf, Lang, Meran 2007, 1414). The method where chemotherapy is combined with HCO-HD has proved to be very effective when it comes to renal recovery and producing dialysis independence. Currently, researchers are trying to compare HCO-HD with standard high flux haemodialysis with chemotherapy based on bortezomib. This is being done on patients having de novo MM. Hutchison, Cook, Heyne, Weisel, Billingham, Bradwell, Cockwell 2008, 55) also discovered through a study that when chemotherapy based on bortezomib is combined with HCO-HD it restores renal function early enough. Another study done by Innes, Cuthbert, Russell, Morgan, Burden 1994, 151) made use of a lifetime tree model based on excel which followed from the time a patients presents with myeloma to the time of death. Most of the authors who have conducted studies on the removal of free light chains using various methods have all based on their research on patients who are dependent on dialysis. More studies should be done on those patients who are not dialysis dependent so that better methods of removing the FLCs can be developed. Some studies in the articles reviewed do not show how the researchers handled practice patterns that are directly actionable like dose dialysis management of anemia and the outcome of the patients like hospitalization and mortality. All these are important for the review of the practices and methods used in the various studies (Evans, Hattersley, Hutchison, Mead, Bradwell, Chappel 2006, 77). Generally, the literature reviewed involves several articles many of which confirm that treatment of renal failure is possible through the removal of free light chains by way of extended haemodialysis. Many authors agree that extended haemodialysis is the most effective method to be used in this case as opposed to other methods such as plasma exchange which have many shortcomings. Haemodialysis is able to remove all the free light chains that cannot be removed through other methods previously in use. Other researchers and authors recommend that extended haemodialysis be combined with other methods for purposes of effectiveness. Chemotherapy can be done in combination with extended haemodialysis. Plasmapheresis can also be used in combination with extended dialysis based on the studies performed by some authors (Clark, Stewart, Rock, Sternbach, Sutton, Barrett, Heidenheim, Garg, Churchill, Canadian Apheresis Group 2005, 780). Through the review of literature, it has become clear that many authors do not account for the methodological problems that occur in the various methods they advocate for. Most of the literature on haemodialysis does not give the methods used to take care of the side effects that come with the removal of a lot of fluid such as high blood pressure. These side effects have the potential to cause new complications in the patient even when treatment for renal failure is underway. Another issue that has been unearthed in the review of articles is that authors make assumptions for which they do not provide sufficient evidence. For example in a study done by Chanan-Khan, Kaufman, Mehta, Richardson, Miller, Lonial, Munshi, Schlossman, Tariman, and Singhal 2007, where haemodialysis was used to remove free light chains, the researcher failed to assess the removal of free light chains from serum through ultrafiltration. The author made an assumption that ultrafiltration would succeed but does not prove it. This kind of assumption has the ability to ruin the outcome of an experiment ending into unverified results (Blade, Fernandez-Llama, Bosch, Montoliu, Lens, Montoto, Cases, Darnell, Rozman, Montserrat 1998, 1891). Conclusion In this literature review, effort has been made to analyze various articles on extended haemodialysis for the removal of free light chains in renal failure treatment. The articles reviewed were strict journal articles although a lot of studies have been done and documented in other types of articles and books. The development of literature over time has been examined with articles written about the progressive development and experimentation of the haemodialysis process and equipment being reviewed. The articles reviewed have shown that researchers are deeply interested in the progressive growth and development of haemodialysis processes and the little developments that come with them. As a result studies have documented various experimental operations on the equipment some of which have resulted in diacovery and improvement on the dialyzer. The review also has the results of the analysis of the findings of various authors as obtained from various articles on the topic under study. Many authors agree that the extended haemodialysis method of removing free light chains is the most superior. Previously, other methods were in use but with the coming of haemodialysis many of the problems of free light chain removal have been dealt with. Extended haemodialysis has been found to have the capacity to remove all the free light chains including those that could not be removed through plasma exchange methods. Extended haemodialysis achieves the best results when used in combination with methods such as chemotherapy. Many dialyzers could be used to achieve membrane biding which is an effective way of removing free light chains. Researchers have come up with models for this purpose. Finally, the articles reviewed display some problems in the studies done by the different researchers. These problems include gaps in knowledge, points of disagreement and problems in methodology and assumptions that do not have supporting evidence. All these have been discussed in this paper. Haemodialysis is the most effective method of treating renal failure. Researchers should do more research on how this method can be used more effectively in cases where the patient is not dependent on dialysis since very little information exists on this. Some authors disagree on whether or not extended haemodialysis should be done in combination with chemotherapy or plasmapheresis. Certain authors insist that heamodialysis must be done strictly alone and that where there are deficiencies, further research should be done to cover for them. Other authors argue that it is necessary to combine a number of strategies so that the best results can be achieved. At present however, the most effective results in haemodialysis cannot be achieved when it is done without chemotherapy. Bibliography Blade J, Fernandez-Llama P, Bosch F, Montoliu J, Lens XM, Montoto S, Cases A, Darnell A, Rozman C, Montserrat E (1998): Renal failure in multiple myeloma: Presenting features and predictors of outcome in 94 patients from a single institution.  Bostrom MA, Freedman BI. 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