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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Multiple myeloma &#40;MM&#41; is a plasma cell neoplasm that causes acute renal failure &#40;ARF&#41; in 12&#37;-20&#37; of cases&#44; whether as an initial manifestation of the myeloma or during the course of evolution of the disease following diagnosis&#46;<span class="elsevierStyleSup">1 </span>The survival of these patients will depend on whether or not they recover renal function&#44; not only due to the complications derived from the renal failure itself&#44; but also from the reduced possibility of access to more effective treatments&#46;<span class="elsevierStyleSup">2&#44;3</span> Renal function is not recovered in 75&#37; of dialysis-dependent patients&#44;<span class="elsevierStyleSup">4-7</span> and their mean survival on renal replacement therapy is less than 1 year&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Cast nephropathy is the most common cause of ARF and plays a role in over 55&#37; of cases&#44; and 75&#37; of those that require dialysis&#46;<span class="elsevierStyleSup">9&#44;10</span> The formation of casts in the distal tubules&#44; caused by the deposition of light chains and Tamm-Horsfall protein&#44; is the main cause of renal failure in these patients<span class="elsevierStyleSup">11-14</span>&#59; as such&#44; it is essential to rapidly reduce blood levels of free light chains in order to facilitate the recovery of renal function&#46;<span class="elsevierStyleSup">15</span></p><p class="elsevierStylePara">Chemotherapy treatments for MM have improved greatly in the last decade&#44; and regimens involving bortezomib&#44; melphalan&#44; thalidomide&#44; and lenalidomide have improved the prognosis of these patients&#46;<span class="elsevierStyleSup">16</span> One coadjuvant therapy for this disease has been reducing free light chain levels using extracorporeal purifying techniques&#46; Plasmapheresis has been used for many years to reduce the circulating levels of light chains&#44; although the efficacy of this treatment in recovering renal function has not been clearly demonstrated&#46;<span class="elsevierStyleSup">17</span> This has caused researchers to search for new techniques that can effectively remove light chains and improve the recovery rate of renal function&#46; To this end&#44; Hutchison et al&#44; using high cut-off &#40;HCO&#41; dialysers and long haemodialysis sessions &#40;8 hours&#41;&#44; have achieved good results in these patients&#44; with recovery rates over 60&#37;&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">We present the evolution of six patients with myeloma and acute renal failure that were treated with these HCO filters&#44; as well as the complications that arise with this type of haemodialysis&#44; and review the pros and cons of this technique&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Six patients diagnosed with MM and ARF requiring dialysis and with serum light chain levels &#62;500mg&#47;l were treated with haemodialysis using HCO 1100<span class="elsevierStyleSup">&#174;</span> &#40;1m<span class="elsevierStyleSup">2</span>&#41; or Theralite<span class="elsevierStyleSup">&#174;</span> &#40;2&#46;1m<span class="elsevierStyleSup">2</span>&#41; high cut-off filters made from polyaryl ether sulfone&#47;polyvinyl pyrrolidone &#40;Gambro Dyalisatorem&#44; Henchingen&#44; Germany&#41;&#46;<span class="elsevierStyleSup">19</span> These filters are designed to increase the permeability of substances smaller than 60kD&#46; The only difference between them is the greater surface area of the membrane&#44; which increases the efficacy in removing light chains and produces a greater loss of albumin&#46; We used Theralite<span class="elsevierStyleSup">&#174;</span> &#40;2&#46;1m<span class="elsevierStyleSup">2</span>&#41; filters when they were commercially available&#46; The haemodialysis sessions involved standard haemodialysis monitors&#44; lasted for 8 hours&#44; involved a blood flow of 200ml&#47;min-250ml&#47;min&#44; and had an ultrapure dialysate flow rate of 500ml&#47;min&#46; Sodium heparin was applied at 3000IU to start with&#44; and 500IU at each hour&#46; At the end of each session&#44; 20&#37; albumin was administered &#40;100cc&#41; along with monosodium phosphate &#40;10ml&#41; and magnesium sulphate &#40;10ml&#41;&#44; following the protocol set out by Hutchison et al&#46;<span class="elsevierStyleSup">20</span> The goal was to perform 5 sessions on consecutive days&#44; followed by sessions on alternating days until renal function was recovered or until light chain levels fell below 500mg&#47;l&#46; Ultrafiltration was programmed according to the clinical needs of each patient&#46;</p><p class="elsevierStylePara">Before and after each session&#44; mean free light chain levels were measured in terms of mg&#47;l using nephelometry &#40;FREELITE<span class="elsevierStyleSup">&#174;</span>&#59; The Binding Site&#44; Birmingham&#44; UK&#41;&#44;<span class="elsevierStyleSup">21</span> and creatinine&#44; albumin&#44; phosphorous&#44; calcium&#44; and magnesium were measured before each session&#46; These measurements were also taken after each session in the first patient&#46; In cases requiring a renal biopsy&#44; an analysis was performed using a light microscope and immunofluorescence with standard techniques&#44; including the detection of anti-kappa and lambda light chain antibodies by immunofluorescence&#46; We also used a Congo red stain test&#46;</p><p class="elsevierStylePara">At the same time&#44; patients were treated with chemotherapy regimens according to the protocols of the haematology department&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Three men and three women were admitted to the nephrology department for ARF of an unknown cause and were finally diagnosed with MM&#46; The characteristics of the patients are summarised in Table 1&#46; Three patients were younger than 60 years&#44; and the other three were older than 70&#46; The initial symptoms were bone pain in four cases&#44; one patient sought treatment for constitutional syndrome&#44; and the sixth patient was admitted under the diagnosis of unconfirmed pancreatitis and renal failure&#46; The start of symptoms varied greatly&#44; between 7 days and over a year &#40;6<span class="elsevierStyleSup">th</span> patient&#41;&#46; In this patient&#44; a review of the clinical history revealed that a monoclonal gammopathy and bone infarcts had been detected one year before&#44; requiring health care&#44; but with an incomplete analysis&#46; The patients that took the longest time to be diagnosed were those that did not recover renal function&#46;</p><p class="elsevierStylePara">Three patients had kappa light chain myeloma&#44; two had lambda IgG myeloma&#44; and one had IgA kappa myeloma&#46; The bone marrow was infiltrated to a varying degree by plasma cells of an anomalous phenotype that are characteristic of the disease&#46; Four patients underwent a renal biopsy&#58; two were diagnosed with cast nephropathy and the other two were diagnosed with cast nephropathy and light chain deposition disease&#46; Immunofluorescence was positive in glomerular samples for light chains in two of the deposition disease cases&#44; and in the tubules and cylinders of all four cases&#46; Interstitial damage was mild&#44; and tubular reactivity with marked regenerative changes was similar in all cases&#46; None of the Congo red stain tests resulted positive&#46; One patient refused the biopsy &#40;case 3&#41;&#44; and the health of another &#40;case 4&#41; negated that possibility&#46; Proteinuria ranged between 6680mg&#47;dl and 570mg&#47;dl&#44; with no correlation observed with serum free light chain levels or histological findings&#46;</p><p class="elsevierStylePara">The number of days of hospitalisation&#44; days to diagnosis&#44; days to start of HCO-HD&#44; as well as the number of days elapsed between hospitalisation and the start of chemotherapy are shown in Table 2&#46; The first three patients were treated with vincristine&#44; adriamycin&#44; and dexamethasone&#44; and the last three were given bortezomib and melphalan and&#47;or prednisone&#44; according to the protocols of the haematology department&#46;</p><p class="elsevierStylePara">It total&#44; the six patients underwent 90 sessions of haemodialysis&#44; with a range of 6-40 sessions each&#46; The HCO-HD was interrupted due to&#58; a&#41; renal function recovery in three cases &#40;cases 1&#44; 3&#44; and 5&#41;&#59; b&#41; in case 2&#44; the start of HCO-HD was delayed several days since the patient had a large inguinal haematoma following catheterisation of the femoral vein&#44; and <span class="elsevierStyleItalic">a posteriori</span> analysis showed that light chain levels had fallen below 500mg&#47;l&#59; c&#41; in case 4&#44; treatment was interrupted upon finding that the patient&#8217;s light chain levels remained above 700mg&#47;l and anuria continued even after 7 sessions of haemodialysis&#59; and d&#41; in case 6&#44; treatment was discontinued after 40 sessions of HCO-HD and three cycles of bortezomib and prednisone in the absence of a response&#44; with light chains remaining at 2760mg&#47;l and persistent oliguria&#46;</p><p class="elsevierStylePara">The percentage reduction in light chain levels from the start of treatment to the end of treatment in each patient is summarised in Figure 1&#44; and was very high in all patients except for patient 6&#44; who did not respond to chemotherapy treatment&#44; with a small reduction in light chain levels &#40;12&#46;6&#37;&#41;&#46; In the other five patients&#44; levels decreased by over 65&#37;&#46; In 56 sessions in which pre and post-HD light chain levels were measured&#44; the mean percentage reduction in light chain levels was 54&#46;98&#37;&#177;17&#46;27&#37; &#40;Figure 2 and Figure 3&#41;&#46; There were no differences in the reduction of lambda and kappa light chains &#40;kappa&#58; 53&#46;52&#37;&#177;18&#46;6&#37; vs lambda 57&#46;82&#37;&#177;14&#46;2&#37;&#41;&#44; or between results when using 1&#46;1m<span class="elsevierStyleSup">2</span> HCO or 2&#46;2m<span class="elsevierStyleSup">2</span> Theralite<span class="elsevierStyleSup">&#174;</span> filters &#40;56&#37;&#177;19&#37; vs 53&#37;&#177;15&#37;&#44; respectively&#41;&#46;</p><p class="elsevierStylePara">In 25 haemodialysis sessions &#40;28&#37;&#41;&#44; several complications&#47;events were registered&#46; These are discussed in Table 3&#46; On 12 occasions &#40;48&#37;&#41;&#44; the complications were due to system coagulations &#40;8 episodes in patient 6&#41;&#44; requiring a suspension of the session on three occasions&#46; Reduced flow and catheter obstruction were the causes of 8 other episodes &#40;32&#37;&#41;&#46; Other complications were irrelevant&#46;</p><p class="elsevierStylePara">There were no major changes in predialysis albumin levels when using this method&#44; although patients that were treated using the 2&#46;1m<span class="elsevierStyleSup">2</span> Theralite<span class="elsevierStyleSup">&#174;</span> filter had a greater decrease in albumin&#44; requiring increased doses after dialysis &#40;cases 5 and 6&#41;&#46; Although calcium&#44; phosphorous&#44; and magnesium levels were slightly reduced in several cases&#44; this change had no clinical significance &#40;Table 4&#41;&#46; Other complications in the evolution of our study patients were&#58; two infections &#40;one resulted in a positive blood culture for <span class="elsevierStyleItalic">Escherichia coli</span>&#44; the other one testing negative&#41; and one stroke with complete recovery&#46;</p><p class="elsevierStylePara">In three patients&#44; renal function was recovered &#40;cases 1&#44; 3&#44; and 5&#41;&#44; and these patients remain alive and free of dialysis&#46; Case 1 received a bone marrow transplant and has had favourable evolution for three and a half years&#59; case 3 has been monitored for two years 8 months&#44; and case 5 for 8 months&#46; Of the three cases that did not recover renal function&#44; one patient died 4 months after starting haemodialysis&#59; in the other two cases&#44; the patients are still alive&#44; although they continue to depend on dialysis &#40;case 2&#58; 2 years&#44; 10 months&#59; case 6&#58; 4 months&#41;&#46; In the two cases that did not recover renal function and had undergone a renal biopsy&#44; cast nephropathy was accompanied by deposition disease&#44; whereas in the two cases that underwent a biopsy and recovered renal function&#44; the cast nephropathy was the sole diagnosis&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Based on our experience&#44; patients with MM and ARF with cast nephropathy can recover renal function through combined treatment with chemotherapy and long haemodialysis sessions with HCO filters&#44; as occurred in at least 50&#37; of the patients in our small study&#46;</p><p class="elsevierStylePara">Recent studies have demonstrated that a rapid decrease in free light chain levels with chemotherapy and extracorporeal techniques is associated with recovered renal function&#46;<span class="elsevierStyleSup">15&#44;22-24</span> Several studies have evaluated the efficacy of plasmapheresis in the treatment of myeloma-related renal failure&#46; The study by Zucchelli et al&#44;<span class="elsevierStyleSup">23</span> and more importantly&#44; the study by Johnson<span class="elsevierStyleSup">24</span> demonstrated a better patient evolution in those cases that were treated with plasmapheresis vs those that were not&#59; however&#44; the small sample size&#44; the fact that not all patients had cast nephropathy&#44; and the use of different dialysis methods significantly limited the conclusions made in this study&#46; Afterwards&#44; Clark<span class="elsevierStyleSup">17 </span>published a randomised&#44; controlled study involving 97 patients&#44; the largest study available in the literature&#46; In this study&#44; plasmapheresis did not achieve superior results in terms of death&#44; dependence on dialysis&#44; and glomerular filtration rate &#40;&#60;30&#37;ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#41;&#46; However&#44; Leung<span class="elsevierStyleSup">15</span> found that plasmapheresis was effective at recovering renal function &#40;mean time&#58; 2 months&#41; if the renal damage was due to cast nephropathy and the level of free light chains decreased by at least 50&#37;&#46; In summary&#44; the efficacy of plasmapheresis in myeloma kidney is uncertain at best&#44; and has yet to be fully upheld as a valid treatment after the publication of only a small number of studies with few patients&#46; The reason for this is that plasmapheresis only purifies the intravascular space &#40;17&#37;&#41; and not at the quantity necessary to provide a benefit to many patients&#44; since the reduction in light chain levels depends primarily on the level of production&#46;<span class="elsevierStyleSup">5</span> Furthermore&#44; plasmapheresis cannot be sustained for a very long time&#46;</p><p class="elsevierStylePara">Since 2007&#44; the use of long haemodialysis sessions with membranes that are permeable to proteins has been proposed in order to increase the extraction rate of light chains up to 90&#37; during three weeks&#46;<span class="elsevierStyleSup">20</span> In this study&#44; HCO filters &#40;Gambro&#41; with a cut-off of 45kD were superior to four different high-flux dialysers &#40;10kD&#41; and two super-flux dialysers &#40;20kD&#41; in clearing light chains &#40;22&#46;5-31kD&#41;&#46; In this same study&#44; the HCO filter was tested in 11 patients with myeloma and requiring haemodialysis who underwent different chemotherapies&#46; Of the 11 patients diagnosed with cast nephropathy based on a renal biopsy&#44; 5 underwent dialysis on a daily basis for one week and afterwards on alternating days&#59; 3 recovering renal function&#46; In the 2 patients that did not recover renal function&#44; infections forced an interruption of the chemotherapy provided&#44; with a consequent rebound in light chain levels&#46; Later&#44; these same authors reported their experience with 19 patients with renal biopsies showing cast nephropathy&#44; 13 of which recovered renal function&#46; Of the 6 patients in which chemotherapy had to be suspended&#44; only one recovered renal function&#44; which appears to suggest that the extraction of light chains using this method is only useful when accompanied by a response to chemotherapy&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">Following the first experience by Hutchison et al&#44; we started treating patients with MM and ARF from cast nephropathy with this method of haemodialysis&#44; with similar results to those from previous authors&#46; In our six patients&#44; the extraction of light chains in each long haemodialysis session with HCO filters reduced light chain levels by 53&#37;-57&#37;&#44; similar to the results reported by Hutchison&#46; At the end of the treatment&#44; our patients had experienced decreases of over 70&#37; over the initial values&#44; except for patient number 6&#44; who&#44; despite the fact that haemodialysis was effective in reducing light chain levels&#44; did not respond to chemotherapy and never recovered renal function&#44; as occurred in Hutchison&#8217;s patients&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">We did not observe severe complications during haemodialysis sessions in our study&#44; and with the replacement of lost albumin&#44; calcium&#44; phosphates&#44; and magnesium&#44; we reached acceptable levels in all these parameters&#46; The use of 2&#46;1m<span class="elsevierStyleSup">2</span> filters did result in a greater loss of albumin&#44; which required increased doses to replenish albumin levels after dialysis sessions&#44; using a double filter&#46;<span class="elsevierStyleSup">25</span> The two infectious complications produced were not significant&#44; and did not require halting the chemotherapy regimen&#46;</p><p class="elsevierStylePara">With regard to the recovery of renal function&#44; our results are similar to Hutchison&#8217;s<span class="elsevierStyleSup">18</span>&#58; approximately 60&#37; of patients recovered renal function using this technique&#46;<span class="elsevierStyleSup">22 </span>Several factors influenced these results&#58; 1&#41; the time elapsed between the start of symptoms and the diagnosis of myeloma&#46; In our study&#44; the three patients that did not recover renal function were those that had suffered symptoms for the longest amount of time &#40;60 days&#44; 120 days&#44; and 1 year&#41;&#46; 2&#41; Histological findings&#58; the 2 patients that underwent a renal biopsy and did not recover renal function had deposition disease&#44; in addition to cast nephropathy&#46; This situation involves a poor prognosis and short life expectancy&#46;<span class="elsevierStyleSup">26</span> 3&#41; The speed with which chemotherapy treatment is started and the response to this treatment&#46; 4&#41; The efficacy in removing light chains in haemodialysis using high cut-off filters&#46; The possibility of recovery was 80&#37; in patients whose light chain levels decreased by 60&#37; after three weeks of treatment&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">There is still no proven evidence that this technique clearly contributes to improve survival in patients with MM and cast nephropathy&#44; or that this type of treatment is superior to plasmapheresis&#44; which has not demonstrated its effectiveness either&#46; Currently&#44; a randomised controlled study &#40;EuLITE&#41; is underway&#44; involving 90 newly diagnosed patients with myeloma caused by cast nephropathy and dialysis-dependent renal failure&#46; All patients will receive bortezomib and will be randomised to treatment with standard haemodialysis or HCO filter haemodialysis&#46; The primary variable is independence from dialysis after three months of treatment&#46;<span class="elsevierStyleSup">27</span> If results are favourable for this technique&#44; it will then be compared with plasmapheresis&#46;</p><p class="elsevierStylePara">Additionally&#44; one limitation for the use of this technique is its high economic cost&#46; Grima<span class="elsevierStyleSup">28</span> recently presented a cost-effectiveness model comparing the treatment of myeloma kidney with HCO filters vs standard haemodialysis&#46; This study found that the treatment of myeloma kidney with long haemodialysis sessions using HCO filters could substantially improve renal recovery in patients with multiple myeloma&#44; compared to the standard haemodialysis&#46; This results in an improved life expectancy and overall savings&#44; without the need for chronic haemodialysis&#46; The model predicts a mean survival of 19&#46;92 months in patients treated with standard haemodialysis vs 33&#46;9 months using the new technique&#44; with a total savings of 6000 pounds sterling per patient&#46;</p><p class="elsevierStylePara">In conclusion&#44; the poor prognosis of patients with MM and ARF due to cast nephropathy requiring dialysis&#44; the relationship between reduced light chain levels and the recovery of renal function suggest the potential benefit of early chemotherapy combined with a method for the extra-corporeal removal of light chains that is effective and can be maintained over time&#46; Long haemodialysis sessions with HCO filters are a reasonable option&#44; although new studies involving new chemotherapy agents and new direct extraction methods of light chains are needed&#46;</p><p class="elsevierStylePara">The authors declare potential conflicts of interest&#58;</p><p class="elsevierStylePara">The author&#40;s&#41; are paid for conferences&#46;</p><p class="elsevierStylePara">The author&#40;s&#41; receive a travel bursary&#47;allowance&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26255&#95;en&#95;t111094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26255_en_t111094.jpg" alt="Characteristics of the six patients diagnosed with multiple myeloma"></img></a></p><p class="elsevierStylePara">Table 1&#46; Characteristics of the six patients diagnosed with multiple myeloma</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26256&#95;en&#95;t211094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26256_en_t211094.jpg" alt="Days to diagnosis and to treatment with HCO&#44; chemotherapy used in the six patients diagnosed with multiple myeloma"></img></a></p><p class="elsevierStylePara">Table 2&#46; Days to diagnosis and to treatment with HCO&#44; chemotherapy used in the six patients diagnosed with multiple myeloma</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26257&#95;en&#95;t311094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26257_en_t311094.jpg" alt="Complications in HCO haemodialysis "></img></a></p><p class="elsevierStylePara">Table 3&#46; Complications in HCO haemodialysis </p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26258&#95;en&#95;t411094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26258_en_t411094.jpg" alt="Maximum&#44; minimum&#44; mean&#44; and standard deviation of phosphorous&#44; calcium&#44; magnesium&#44; albumin&#44; and creatinine values before haemodialysis sessions"></img></a></p><p class="elsevierStylePara">Table 4&#46; Maximum&#44; minimum&#44; mean&#44; and standard deviation of phosphorous&#44; calcium&#44; magnesium&#44; albumin&#44; and creatinine values before haemodialysis sessions</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26260&#95;en&#95;f111094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26260_en_f111094.jpg" alt="Percentage reduction in free light chain levels in the six patients treated with HCO haemodialysis at the end of treatment"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Percentage reduction in free light chain levels in the six patients treated with HCO haemodialysis at the end of treatment</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26262&#95;en&#95;f211094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26262_en_f211094.jpg" alt="Serum free light chain levels before and after haemodialysis in the six patients"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Serum free light chain levels before and after haemodialysis in the six patients</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26263&#95;en&#95;f311094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26263_en_f311094.jpg" alt="Percentage reduction in serum free light chains in the haemodialysis sessions of all six patients"></img></a></p><p class="elsevierStylePara">Figure 3&#46; Percentage reduction in serum free light chains in the haemodialysis sessions of all six patients</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducci&#243;n&#58;</span> El fracaso renal agudo &#40;FRA&#41; en el mieloma m&#250;ltiple &#40;MM&#41; se presenta entre el 12-20&#37; de los casos y la supervivencia de estos pacientes depende de la recuperaci&#243;n de la funci&#243;n renal&#46; El 75&#37; de los pacientes dependientes de di&#225;lisis no recuperan la funci&#243;n renal y su supervivencia media en situaci&#243;n de tratamiento sustitutivo es inferior al a&#241;o&#46; La&#160;nefropat&#237;a por cilindros es la causa m&#225;s frecuente de fracaso renal y acontece en m&#225;s del 55&#37; de los casos&#44; y en el 75&#37; de aquellos que requieren di&#225;lisis&#46; Para facilitar la recuperaci&#243;n de la funci&#243;n renal es imprescindible la disminuci&#243;n r&#225;pida de los niveles en sangre de cadenas ligeras&#46; Una medida coadyuvante al tratamiento espec&#237;fico de la enfermedad ha sido la reducci&#243;n de estas cadenas ligeras con plasmaf&#233;resis&#44; sin que se haya demostrado claramente su eficacia&#44; por lo que se ha propuesto el uso de hemodi&#225;lisis largas con filtros de alto poro &#40;HCO&#41;&#44;&#160;consiguiendo una tasa de recuperaci&#243;n superior&#160;al 60&#37;&#46; Presentamos la evoluci&#243;n en seis casos de pacientes con mieloma y fracaso renal agudo que fueron tratados con&#160;dichos filtros HCO&#44; las complicaciones con este tipo de hemodi&#225;lisis y revisamos los pros y los contras de esta t&#233;cnica&#46; <span class="elsevierStyleBold">Metodolog&#237;a&#58;</span> Seis pacientes diagnosticados de MM y FRA con necesidad de di&#225;lisis y niveles circulantes de cadena ligera por encima de 500 mg&#47;l fueron tratados con hemodi&#225;lisis de 8 horas con filtro HCO&#46; Al comienzo y al final de cada sesi&#243;n se med&#237;an las cadenas ligeras s&#233;ricas por nefelometr&#237;a&#44; as&#237; como otros par&#225;metros&#46; Al mismo tiempo los pacientes fueron tratados con quimioterapia seg&#250;n protocolos&#46; <span class="elsevierStyleBold">Resultados&#58;&#160;</span>A<span class="elsevierStyleBold"> </span>tres hombres y tres mujeres diagnosticados de MM y FRA&#44;&#160;con&#160;inicio de los s&#237;ntomas muy variable&#44; desde 7 d&#237;as a m&#225;s de un a&#241;o&#44; se les realiz&#243; 90 sesiones de hemodi&#225;lisis largas con filtros HCO con un rango de entre 6 y 40 sesiones&#46; El porcentaje de reducci&#243;n de las cadenas ligeras desde el inicio del tratamiento&#160;hasta su finalizaci&#243;n fue el 65&#37; de media&#44; excepto en un paciente&#44; que fue del 12&#44;6&#37;&#46; La media del porcentaje de reducci&#243;n de la cadena ligera por sesi&#243;n fue de 54&#44;98 &#177; 17&#44;27&#37;&#46;&#160;En el 28&#37; de las sesiones se registr&#243; alguna complicaci&#243;n&#46; El 48&#37; de las complicaciones se debieron a la coagulaci&#243;n del sistema&#46;&#160;No hubo grandes cambios en los niveles de alb&#250;mina predi&#225;lisis&#44;&#160;calcio&#44; f&#243;sforo y magnesio&#44; aunque en alg&#250;n caso se registraron valores disminuidos que no comportaron relevancia cl&#237;nica&#46;&#160;En tres pacientes la funci&#243;n renal se recuper&#243; y permanecen vivos e independientes de la di&#225;lisis&#46; En los casos biopsiados y que recuperaron funci&#243;n renal&#44; la nefropat&#237;a por cilindros fue pura&#46; Los pacientes que tardaron m&#225;s en ser diagnosticados fueron los pacientes que no recuperaron funci&#243;n renal&#44; y cuando se les efectu&#243; biopsia el diagn&#243;stico fue de nefropat&#237;a por cilindros m&#225;s enfermedad por dep&#243;sitos&#46; <span class="elsevierStyleBold">Conclusi&#243;n&#58;</span> En nuestra experiencia&#44;&#160;la hemodi&#225;lisis larga con filtros HCO es una alternativa razonable en el FRA causado por nefropat&#237;a por cilindros&#44; alcanzando en nuestros casos una tasa de recuperaci&#243;n del 50&#37;&#46; En la recuperaci&#243;n influyeron&#58; el tiempo transcurrido desde el inicio de los s&#237;ntomas al diagn&#243;stico de mieloma&#44; los hallazgos histol&#243;gicos&#44; la rapidez de instauraci&#243;n del tratamiento quimioter&#225;pico y su respuesta&#160;y&#160;la eficacia en la extracci&#243;n de cadenas ligeras&#46; En cualquier caso&#44; son necesarios nuevos estudios con nuevos agentes quimioter&#225;picos y las nuevas t&#233;cnicas&#160;de extracci&#243;n directa de cadenas ligeras&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction&#58; </span>Acute renal failure &#40;ARF&#41; occurs in 12&#37;-20&#37; of all multiple myeloma &#40;MM&#41; cases&#44; and the survival of these patients depends on renal function recovery&#46; Renal function is not recovered in 75&#37; of dialysis-dependent patients&#44; and their mean survival with replacement therapy is less than one year&#46; Renal tubular disease is the most frequent cause of renal failure&#46; It is present in more than 55&#37; of renal failure cases and in 75&#37; of those requiring dialysis&#46; Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function&#46; One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis&#44; but its efficacy has not yet been clearly proven&#46; Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers &#40;HCO-HD&#41;&#44; obtaining a recovery rate of more than 60&#37;&#46; We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis&#46; Then&#44; we review the pros and cons of this technique&#46; <span class="elsevierStyleBold">Method&#58; </span>Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500mg&#47;l were treated with 8-hour haemodialysis sessions with an HCO-HD filter&#46; Before and after each session&#44; serum free light chain levels were measured by nephelometry&#59; other parameters were recorded as well&#46; At the same time&#44; patients underwent chemotherapy according to protocols&#46; <span class="elsevierStyleBold">Results&#58; </span>The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable&#44; from 7 days to more than 1 year&#46; We performed 90 extended sessions with HCO-HD filters&#44; and each patient underwent between 6 and 40 sessions&#46; Free light chain levels decreased by a mean of 65&#37; between treatment onset and completion&#44; except in one patient who experienced a 12&#46;6&#37; reduction&#46; The mean percentage of reduction of light chain levels per session was 54&#46;98&#37;&#177;17&#46;27&#37;&#46; A complication occurred during 28&#37; of the sessions&#46; Of these complications&#44; 48&#37; were due to system coagulation&#46; There were no major changes in pre-dialysis albumin&#44; calcium&#44; phosphorous or magnesium levels&#44; although lower values that were not clinically relevant were recorded in one case&#46; Renal function was recovered in 3 patients&#44; they are alive and dialysis-free&#46; In biopsied cases that recovered renal function&#44; the specimen showed tubular nephropathy only&#46; Those patients who took longer to be diagnosed did not recover their renal function&#44; and when biopsied&#44; they were diagnosed with renal tubular disease and light chain deposition disease&#46; <span class="elsevierStyleBold">Conclusion&#58; </span>We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease&#44; and achieved a recovery rate of 50&#37; in our cases&#46; Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis&#44; histological findings&#44; promptness of starting chemotherapy&#44; response to chemotherapy&#44; and effectiveness of light chain extraction&#46; In any case&#44; further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques&#46;&#160;</p>"
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                  "referenciaCompleta" => "Clark WF, Stewart AK, Rock GA, Sternbach M, Sutton DM, Barrett BJ, et al. Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trial. Ann Intern Med 2005;143:777. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16330788" target="_blank">[Pubmed]</a>"
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                    0 => null
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                    0 => null
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                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
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                0 => array:3 [
                  "referenciaCompleta" => "Hutchison CA, Bradwell A, Cook M, Basnayake K, Basu S, Harding S, et al. Treatment of Acute Renal Failure Secondary to Multiple Myeloma with Chemotherapy and Extended High Cut-Off Hemodialysis. Clin J Am Soc Nephrol 2009;4(4):745-54. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19339414" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
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Haemodialysis using high cut-off dialysers for treating acute renal failure in multiple myeloma
Tratamiento con hemodiálisis del fracaso renal agudo en el mieloma múltiple con filtros de alto poro (high cut-off)
Guillermo Martín-Reyesa, Remedios Toledo-Rojasa, Álvaro Torres-de Ruedaa, Eugenia Sola-Moyanoa, Lourdes Blanca-Martosa, Laura Fuentes-Sáncheza, M. Dolores Martínez-Estebana, M. José Díez-de los Ríosb, Alicia Bailén-Garcíac, Miguel González-Molinaa, Isabel García-Gonzálezd
a Servicio de Nefrología, Hospital Regional Universitario Carlos Haya, Málaga,
b Laboratorio de Análisis Clínicos, Hospital Regional Universitario Carlos Haya, Málaga,
c Servicio de Hematología, Hospital Regional Universitario Carlos Haya, Málaga,
d Servicio de Anatomía Patológica, Hospital Regional Universitario Carlos Haya, Málaga,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Multiple myeloma &#40;MM&#41; is a plasma cell neoplasm that causes acute renal failure &#40;ARF&#41; in 12&#37;-20&#37; of cases&#44; whether as an initial manifestation of the myeloma or during the course of evolution of the disease following diagnosis&#46;<span class="elsevierStyleSup">1 </span>The survival of these patients will depend on whether or not they recover renal function&#44; not only due to the complications derived from the renal failure itself&#44; but also from the reduced possibility of access to more effective treatments&#46;<span class="elsevierStyleSup">2&#44;3</span> Renal function is not recovered in 75&#37; of dialysis-dependent patients&#44;<span class="elsevierStyleSup">4-7</span> and their mean survival on renal replacement therapy is less than 1 year&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Cast nephropathy is the most common cause of ARF and plays a role in over 55&#37; of cases&#44; and 75&#37; of those that require dialysis&#46;<span class="elsevierStyleSup">9&#44;10</span> The formation of casts in the distal tubules&#44; caused by the deposition of light chains and Tamm-Horsfall protein&#44; is the main cause of renal failure in these patients<span class="elsevierStyleSup">11-14</span>&#59; as such&#44; it is essential to rapidly reduce blood levels of free light chains in order to facilitate the recovery of renal function&#46;<span class="elsevierStyleSup">15</span></p><p class="elsevierStylePara">Chemotherapy treatments for MM have improved greatly in the last decade&#44; and regimens involving bortezomib&#44; melphalan&#44; thalidomide&#44; and lenalidomide have improved the prognosis of these patients&#46;<span class="elsevierStyleSup">16</span> One coadjuvant therapy for this disease has been reducing free light chain levels using extracorporeal purifying techniques&#46; Plasmapheresis has been used for many years to reduce the circulating levels of light chains&#44; although the efficacy of this treatment in recovering renal function has not been clearly demonstrated&#46;<span class="elsevierStyleSup">17</span> This has caused researchers to search for new techniques that can effectively remove light chains and improve the recovery rate of renal function&#46; To this end&#44; Hutchison et al&#44; using high cut-off &#40;HCO&#41; dialysers and long haemodialysis sessions &#40;8 hours&#41;&#44; have achieved good results in these patients&#44; with recovery rates over 60&#37;&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">We present the evolution of six patients with myeloma and acute renal failure that were treated with these HCO filters&#44; as well as the complications that arise with this type of haemodialysis&#44; and review the pros and cons of this technique&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Six patients diagnosed with MM and ARF requiring dialysis and with serum light chain levels &#62;500mg&#47;l were treated with haemodialysis using HCO 1100<span class="elsevierStyleSup">&#174;</span> &#40;1m<span class="elsevierStyleSup">2</span>&#41; or Theralite<span class="elsevierStyleSup">&#174;</span> &#40;2&#46;1m<span class="elsevierStyleSup">2</span>&#41; high cut-off filters made from polyaryl ether sulfone&#47;polyvinyl pyrrolidone &#40;Gambro Dyalisatorem&#44; Henchingen&#44; Germany&#41;&#46;<span class="elsevierStyleSup">19</span> These filters are designed to increase the permeability of substances smaller than 60kD&#46; The only difference between them is the greater surface area of the membrane&#44; which increases the efficacy in removing light chains and produces a greater loss of albumin&#46; We used Theralite<span class="elsevierStyleSup">&#174;</span> &#40;2&#46;1m<span class="elsevierStyleSup">2</span>&#41; filters when they were commercially available&#46; The haemodialysis sessions involved standard haemodialysis monitors&#44; lasted for 8 hours&#44; involved a blood flow of 200ml&#47;min-250ml&#47;min&#44; and had an ultrapure dialysate flow rate of 500ml&#47;min&#46; Sodium heparin was applied at 3000IU to start with&#44; and 500IU at each hour&#46; At the end of each session&#44; 20&#37; albumin was administered &#40;100cc&#41; along with monosodium phosphate &#40;10ml&#41; and magnesium sulphate &#40;10ml&#41;&#44; following the protocol set out by Hutchison et al&#46;<span class="elsevierStyleSup">20</span> The goal was to perform 5 sessions on consecutive days&#44; followed by sessions on alternating days until renal function was recovered or until light chain levels fell below 500mg&#47;l&#46; Ultrafiltration was programmed according to the clinical needs of each patient&#46;</p><p class="elsevierStylePara">Before and after each session&#44; mean free light chain levels were measured in terms of mg&#47;l using nephelometry &#40;FREELITE<span class="elsevierStyleSup">&#174;</span>&#59; The Binding Site&#44; Birmingham&#44; UK&#41;&#44;<span class="elsevierStyleSup">21</span> and creatinine&#44; albumin&#44; phosphorous&#44; calcium&#44; and magnesium were measured before each session&#46; These measurements were also taken after each session in the first patient&#46; In cases requiring a renal biopsy&#44; an analysis was performed using a light microscope and immunofluorescence with standard techniques&#44; including the detection of anti-kappa and lambda light chain antibodies by immunofluorescence&#46; We also used a Congo red stain test&#46;</p><p class="elsevierStylePara">At the same time&#44; patients were treated with chemotherapy regimens according to the protocols of the haematology department&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Three men and three women were admitted to the nephrology department for ARF of an unknown cause and were finally diagnosed with MM&#46; The characteristics of the patients are summarised in Table 1&#46; Three patients were younger than 60 years&#44; and the other three were older than 70&#46; The initial symptoms were bone pain in four cases&#44; one patient sought treatment for constitutional syndrome&#44; and the sixth patient was admitted under the diagnosis of unconfirmed pancreatitis and renal failure&#46; The start of symptoms varied greatly&#44; between 7 days and over a year &#40;6<span class="elsevierStyleSup">th</span> patient&#41;&#46; In this patient&#44; a review of the clinical history revealed that a monoclonal gammopathy and bone infarcts had been detected one year before&#44; requiring health care&#44; but with an incomplete analysis&#46; The patients that took the longest time to be diagnosed were those that did not recover renal function&#46;</p><p class="elsevierStylePara">Three patients had kappa light chain myeloma&#44; two had lambda IgG myeloma&#44; and one had IgA kappa myeloma&#46; The bone marrow was infiltrated to a varying degree by plasma cells of an anomalous phenotype that are characteristic of the disease&#46; Four patients underwent a renal biopsy&#58; two were diagnosed with cast nephropathy and the other two were diagnosed with cast nephropathy and light chain deposition disease&#46; Immunofluorescence was positive in glomerular samples for light chains in two of the deposition disease cases&#44; and in the tubules and cylinders of all four cases&#46; Interstitial damage was mild&#44; and tubular reactivity with marked regenerative changes was similar in all cases&#46; None of the Congo red stain tests resulted positive&#46; One patient refused the biopsy &#40;case 3&#41;&#44; and the health of another &#40;case 4&#41; negated that possibility&#46; Proteinuria ranged between 6680mg&#47;dl and 570mg&#47;dl&#44; with no correlation observed with serum free light chain levels or histological findings&#46;</p><p class="elsevierStylePara">The number of days of hospitalisation&#44; days to diagnosis&#44; days to start of HCO-HD&#44; as well as the number of days elapsed between hospitalisation and the start of chemotherapy are shown in Table 2&#46; The first three patients were treated with vincristine&#44; adriamycin&#44; and dexamethasone&#44; and the last three were given bortezomib and melphalan and&#47;or prednisone&#44; according to the protocols of the haematology department&#46;</p><p class="elsevierStylePara">It total&#44; the six patients underwent 90 sessions of haemodialysis&#44; with a range of 6-40 sessions each&#46; The HCO-HD was interrupted due to&#58; a&#41; renal function recovery in three cases &#40;cases 1&#44; 3&#44; and 5&#41;&#59; b&#41; in case 2&#44; the start of HCO-HD was delayed several days since the patient had a large inguinal haematoma following catheterisation of the femoral vein&#44; and <span class="elsevierStyleItalic">a posteriori</span> analysis showed that light chain levels had fallen below 500mg&#47;l&#59; c&#41; in case 4&#44; treatment was interrupted upon finding that the patient&#8217;s light chain levels remained above 700mg&#47;l and anuria continued even after 7 sessions of haemodialysis&#59; and d&#41; in case 6&#44; treatment was discontinued after 40 sessions of HCO-HD and three cycles of bortezomib and prednisone in the absence of a response&#44; with light chains remaining at 2760mg&#47;l and persistent oliguria&#46;</p><p class="elsevierStylePara">The percentage reduction in light chain levels from the start of treatment to the end of treatment in each patient is summarised in Figure 1&#44; and was very high in all patients except for patient 6&#44; who did not respond to chemotherapy treatment&#44; with a small reduction in light chain levels &#40;12&#46;6&#37;&#41;&#46; In the other five patients&#44; levels decreased by over 65&#37;&#46; In 56 sessions in which pre and post-HD light chain levels were measured&#44; the mean percentage reduction in light chain levels was 54&#46;98&#37;&#177;17&#46;27&#37; &#40;Figure 2 and Figure 3&#41;&#46; There were no differences in the reduction of lambda and kappa light chains &#40;kappa&#58; 53&#46;52&#37;&#177;18&#46;6&#37; vs lambda 57&#46;82&#37;&#177;14&#46;2&#37;&#41;&#44; or between results when using 1&#46;1m<span class="elsevierStyleSup">2</span> HCO or 2&#46;2m<span class="elsevierStyleSup">2</span> Theralite<span class="elsevierStyleSup">&#174;</span> filters &#40;56&#37;&#177;19&#37; vs 53&#37;&#177;15&#37;&#44; respectively&#41;&#46;</p><p class="elsevierStylePara">In 25 haemodialysis sessions &#40;28&#37;&#41;&#44; several complications&#47;events were registered&#46; These are discussed in Table 3&#46; On 12 occasions &#40;48&#37;&#41;&#44; the complications were due to system coagulations &#40;8 episodes in patient 6&#41;&#44; requiring a suspension of the session on three occasions&#46; Reduced flow and catheter obstruction were the causes of 8 other episodes &#40;32&#37;&#41;&#46; Other complications were irrelevant&#46;</p><p class="elsevierStylePara">There were no major changes in predialysis albumin levels when using this method&#44; although patients that were treated using the 2&#46;1m<span class="elsevierStyleSup">2</span> Theralite<span class="elsevierStyleSup">&#174;</span> filter had a greater decrease in albumin&#44; requiring increased doses after dialysis &#40;cases 5 and 6&#41;&#46; Although calcium&#44; phosphorous&#44; and magnesium levels were slightly reduced in several cases&#44; this change had no clinical significance &#40;Table 4&#41;&#46; Other complications in the evolution of our study patients were&#58; two infections &#40;one resulted in a positive blood culture for <span class="elsevierStyleItalic">Escherichia coli</span>&#44; the other one testing negative&#41; and one stroke with complete recovery&#46;</p><p class="elsevierStylePara">In three patients&#44; renal function was recovered &#40;cases 1&#44; 3&#44; and 5&#41;&#44; and these patients remain alive and free of dialysis&#46; Case 1 received a bone marrow transplant and has had favourable evolution for three and a half years&#59; case 3 has been monitored for two years 8 months&#44; and case 5 for 8 months&#46; Of the three cases that did not recover renal function&#44; one patient died 4 months after starting haemodialysis&#59; in the other two cases&#44; the patients are still alive&#44; although they continue to depend on dialysis &#40;case 2&#58; 2 years&#44; 10 months&#59; case 6&#58; 4 months&#41;&#46; In the two cases that did not recover renal function and had undergone a renal biopsy&#44; cast nephropathy was accompanied by deposition disease&#44; whereas in the two cases that underwent a biopsy and recovered renal function&#44; the cast nephropathy was the sole diagnosis&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Based on our experience&#44; patients with MM and ARF with cast nephropathy can recover renal function through combined treatment with chemotherapy and long haemodialysis sessions with HCO filters&#44; as occurred in at least 50&#37; of the patients in our small study&#46;</p><p class="elsevierStylePara">Recent studies have demonstrated that a rapid decrease in free light chain levels with chemotherapy and extracorporeal techniques is associated with recovered renal function&#46;<span class="elsevierStyleSup">15&#44;22-24</span> Several studies have evaluated the efficacy of plasmapheresis in the treatment of myeloma-related renal failure&#46; The study by Zucchelli et al&#44;<span class="elsevierStyleSup">23</span> and more importantly&#44; the study by Johnson<span class="elsevierStyleSup">24</span> demonstrated a better patient evolution in those cases that were treated with plasmapheresis vs those that were not&#59; however&#44; the small sample size&#44; the fact that not all patients had cast nephropathy&#44; and the use of different dialysis methods significantly limited the conclusions made in this study&#46; Afterwards&#44; Clark<span class="elsevierStyleSup">17 </span>published a randomised&#44; controlled study involving 97 patients&#44; the largest study available in the literature&#46; In this study&#44; plasmapheresis did not achieve superior results in terms of death&#44; dependence on dialysis&#44; and glomerular filtration rate &#40;&#60;30&#37;ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#41;&#46; However&#44; Leung<span class="elsevierStyleSup">15</span> found that plasmapheresis was effective at recovering renal function &#40;mean time&#58; 2 months&#41; if the renal damage was due to cast nephropathy and the level of free light chains decreased by at least 50&#37;&#46; In summary&#44; the efficacy of plasmapheresis in myeloma kidney is uncertain at best&#44; and has yet to be fully upheld as a valid treatment after the publication of only a small number of studies with few patients&#46; The reason for this is that plasmapheresis only purifies the intravascular space &#40;17&#37;&#41; and not at the quantity necessary to provide a benefit to many patients&#44; since the reduction in light chain levels depends primarily on the level of production&#46;<span class="elsevierStyleSup">5</span> Furthermore&#44; plasmapheresis cannot be sustained for a very long time&#46;</p><p class="elsevierStylePara">Since 2007&#44; the use of long haemodialysis sessions with membranes that are permeable to proteins has been proposed in order to increase the extraction rate of light chains up to 90&#37; during three weeks&#46;<span class="elsevierStyleSup">20</span> In this study&#44; HCO filters &#40;Gambro&#41; with a cut-off of 45kD were superior to four different high-flux dialysers &#40;10kD&#41; and two super-flux dialysers &#40;20kD&#41; in clearing light chains &#40;22&#46;5-31kD&#41;&#46; In this same study&#44; the HCO filter was tested in 11 patients with myeloma and requiring haemodialysis who underwent different chemotherapies&#46; Of the 11 patients diagnosed with cast nephropathy based on a renal biopsy&#44; 5 underwent dialysis on a daily basis for one week and afterwards on alternating days&#59; 3 recovering renal function&#46; In the 2 patients that did not recover renal function&#44; infections forced an interruption of the chemotherapy provided&#44; with a consequent rebound in light chain levels&#46; Later&#44; these same authors reported their experience with 19 patients with renal biopsies showing cast nephropathy&#44; 13 of which recovered renal function&#46; Of the 6 patients in which chemotherapy had to be suspended&#44; only one recovered renal function&#44; which appears to suggest that the extraction of light chains using this method is only useful when accompanied by a response to chemotherapy&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">Following the first experience by Hutchison et al&#44; we started treating patients with MM and ARF from cast nephropathy with this method of haemodialysis&#44; with similar results to those from previous authors&#46; In our six patients&#44; the extraction of light chains in each long haemodialysis session with HCO filters reduced light chain levels by 53&#37;-57&#37;&#44; similar to the results reported by Hutchison&#46; At the end of the treatment&#44; our patients had experienced decreases of over 70&#37; over the initial values&#44; except for patient number 6&#44; who&#44; despite the fact that haemodialysis was effective in reducing light chain levels&#44; did not respond to chemotherapy and never recovered renal function&#44; as occurred in Hutchison&#8217;s patients&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">We did not observe severe complications during haemodialysis sessions in our study&#44; and with the replacement of lost albumin&#44; calcium&#44; phosphates&#44; and magnesium&#44; we reached acceptable levels in all these parameters&#46; The use of 2&#46;1m<span class="elsevierStyleSup">2</span> filters did result in a greater loss of albumin&#44; which required increased doses to replenish albumin levels after dialysis sessions&#44; using a double filter&#46;<span class="elsevierStyleSup">25</span> The two infectious complications produced were not significant&#44; and did not require halting the chemotherapy regimen&#46;</p><p class="elsevierStylePara">With regard to the recovery of renal function&#44; our results are similar to Hutchison&#8217;s<span class="elsevierStyleSup">18</span>&#58; approximately 60&#37; of patients recovered renal function using this technique&#46;<span class="elsevierStyleSup">22 </span>Several factors influenced these results&#58; 1&#41; the time elapsed between the start of symptoms and the diagnosis of myeloma&#46; In our study&#44; the three patients that did not recover renal function were those that had suffered symptoms for the longest amount of time &#40;60 days&#44; 120 days&#44; and 1 year&#41;&#46; 2&#41; Histological findings&#58; the 2 patients that underwent a renal biopsy and did not recover renal function had deposition disease&#44; in addition to cast nephropathy&#46; This situation involves a poor prognosis and short life expectancy&#46;<span class="elsevierStyleSup">26</span> 3&#41; The speed with which chemotherapy treatment is started and the response to this treatment&#46; 4&#41; The efficacy in removing light chains in haemodialysis using high cut-off filters&#46; The possibility of recovery was 80&#37; in patients whose light chain levels decreased by 60&#37; after three weeks of treatment&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">There is still no proven evidence that this technique clearly contributes to improve survival in patients with MM and cast nephropathy&#44; or that this type of treatment is superior to plasmapheresis&#44; which has not demonstrated its effectiveness either&#46; Currently&#44; a randomised controlled study &#40;EuLITE&#41; is underway&#44; involving 90 newly diagnosed patients with myeloma caused by cast nephropathy and dialysis-dependent renal failure&#46; All patients will receive bortezomib and will be randomised to treatment with standard haemodialysis or HCO filter haemodialysis&#46; The primary variable is independence from dialysis after three months of treatment&#46;<span class="elsevierStyleSup">27</span> If results are favourable for this technique&#44; it will then be compared with plasmapheresis&#46;</p><p class="elsevierStylePara">Additionally&#44; one limitation for the use of this technique is its high economic cost&#46; Grima<span class="elsevierStyleSup">28</span> recently presented a cost-effectiveness model comparing the treatment of myeloma kidney with HCO filters vs standard haemodialysis&#46; This study found that the treatment of myeloma kidney with long haemodialysis sessions using HCO filters could substantially improve renal recovery in patients with multiple myeloma&#44; compared to the standard haemodialysis&#46; This results in an improved life expectancy and overall savings&#44; without the need for chronic haemodialysis&#46; The model predicts a mean survival of 19&#46;92 months in patients treated with standard haemodialysis vs 33&#46;9 months using the new technique&#44; with a total savings of 6000 pounds sterling per patient&#46;</p><p class="elsevierStylePara">In conclusion&#44; the poor prognosis of patients with MM and ARF due to cast nephropathy requiring dialysis&#44; the relationship between reduced light chain levels and the recovery of renal function suggest the potential benefit of early chemotherapy combined with a method for the extra-corporeal removal of light chains that is effective and can be maintained over time&#46; Long haemodialysis sessions with HCO filters are a reasonable option&#44; although new studies involving new chemotherapy agents and new direct extraction methods of light chains are needed&#46;</p><p class="elsevierStylePara">The authors declare potential conflicts of interest&#58;</p><p class="elsevierStylePara">The author&#40;s&#41; are paid for conferences&#46;</p><p class="elsevierStylePara">The author&#40;s&#41; receive a travel bursary&#47;allowance&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26255&#95;en&#95;t111094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26255_en_t111094.jpg" alt="Characteristics of the six patients diagnosed with multiple myeloma"></img></a></p><p class="elsevierStylePara">Table 1&#46; Characteristics of the six patients diagnosed with multiple myeloma</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26256&#95;en&#95;t211094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26256_en_t211094.jpg" alt="Days to diagnosis and to treatment with HCO&#44; chemotherapy used in the six patients diagnosed with multiple myeloma"></img></a></p><p class="elsevierStylePara">Table 2&#46; Days to diagnosis and to treatment with HCO&#44; chemotherapy used in the six patients diagnosed with multiple myeloma</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26257&#95;en&#95;t311094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26257_en_t311094.jpg" alt="Complications in HCO haemodialysis "></img></a></p><p class="elsevierStylePara">Table 3&#46; Complications in HCO haemodialysis </p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26258&#95;en&#95;t411094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26258_en_t411094.jpg" alt="Maximum&#44; minimum&#44; mean&#44; and standard deviation of phosphorous&#44; calcium&#44; magnesium&#44; albumin&#44; and creatinine values before haemodialysis sessions"></img></a></p><p class="elsevierStylePara">Table 4&#46; Maximum&#44; minimum&#44; mean&#44; and standard deviation of phosphorous&#44; calcium&#44; magnesium&#44; albumin&#44; and creatinine values before haemodialysis sessions</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26260&#95;en&#95;f111094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26260_en_f111094.jpg" alt="Percentage reduction in free light chain levels in the six patients treated with HCO haemodialysis at the end of treatment"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Percentage reduction in free light chain levels in the six patients treated with HCO haemodialysis at the end of treatment</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26262&#95;en&#95;f211094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26262_en_f211094.jpg" alt="Serum free light chain levels before and after haemodialysis in the six patients"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Serum free light chain levels before and after haemodialysis in the six patients</p><p class="elsevierStylePara"><a href="grande&#47;11094&#95;16025&#95;26263&#95;en&#95;f311094&#46;jpg" class="elsevierStyleCrossRefs"><img src="11094_16025_26263_en_f311094.jpg" alt="Percentage reduction in serum free light chains in the haemodialysis sessions of all six patients"></img></a></p><p class="elsevierStylePara">Figure 3&#46; Percentage reduction in serum free light chains in the haemodialysis sessions of all six patients</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducci&#243;n&#58;</span> El fracaso renal agudo &#40;FRA&#41; en el mieloma m&#250;ltiple &#40;MM&#41; se presenta entre el 12-20&#37; de los casos y la supervivencia de estos pacientes depende de la recuperaci&#243;n de la funci&#243;n renal&#46; El 75&#37; de los pacientes dependientes de di&#225;lisis no recuperan la funci&#243;n renal y su supervivencia media en situaci&#243;n de tratamiento sustitutivo es inferior al a&#241;o&#46; La&#160;nefropat&#237;a por cilindros es la causa m&#225;s frecuente de fracaso renal y acontece en m&#225;s del 55&#37; de los casos&#44; y en el 75&#37; de aquellos que requieren di&#225;lisis&#46; Para facilitar la recuperaci&#243;n de la funci&#243;n renal es imprescindible la disminuci&#243;n r&#225;pida de los niveles en sangre de cadenas ligeras&#46; Una medida coadyuvante al tratamiento espec&#237;fico de la enfermedad ha sido la reducci&#243;n de estas cadenas ligeras con plasmaf&#233;resis&#44; sin que se haya demostrado claramente su eficacia&#44; por lo que se ha propuesto el uso de hemodi&#225;lisis largas con filtros de alto poro &#40;HCO&#41;&#44;&#160;consiguiendo una tasa de recuperaci&#243;n superior&#160;al 60&#37;&#46; Presentamos la evoluci&#243;n en seis casos de pacientes con mieloma y fracaso renal agudo que fueron tratados con&#160;dichos filtros HCO&#44; las complicaciones con este tipo de hemodi&#225;lisis y revisamos los pros y los contras de esta t&#233;cnica&#46; <span class="elsevierStyleBold">Metodolog&#237;a&#58;</span> Seis pacientes diagnosticados de MM y FRA con necesidad de di&#225;lisis y niveles circulantes de cadena ligera por encima de 500 mg&#47;l fueron tratados con hemodi&#225;lisis de 8 horas con filtro HCO&#46; Al comienzo y al final de cada sesi&#243;n se med&#237;an las cadenas ligeras s&#233;ricas por nefelometr&#237;a&#44; as&#237; como otros par&#225;metros&#46; Al mismo tiempo los pacientes fueron tratados con quimioterapia seg&#250;n protocolos&#46; <span class="elsevierStyleBold">Resultados&#58;&#160;</span>A<span class="elsevierStyleBold"> </span>tres hombres y tres mujeres diagnosticados de MM y FRA&#44;&#160;con&#160;inicio de los s&#237;ntomas muy variable&#44; desde 7 d&#237;as a m&#225;s de un a&#241;o&#44; se les realiz&#243; 90 sesiones de hemodi&#225;lisis largas con filtros HCO con un rango de entre 6 y 40 sesiones&#46; El porcentaje de reducci&#243;n de las cadenas ligeras desde el inicio del tratamiento&#160;hasta su finalizaci&#243;n fue el 65&#37; de media&#44; excepto en un paciente&#44; que fue del 12&#44;6&#37;&#46; La media del porcentaje de reducci&#243;n de la cadena ligera por sesi&#243;n fue de 54&#44;98 &#177; 17&#44;27&#37;&#46;&#160;En el 28&#37; de las sesiones se registr&#243; alguna complicaci&#243;n&#46; El 48&#37; de las complicaciones se debieron a la coagulaci&#243;n del sistema&#46;&#160;No hubo grandes cambios en los niveles de alb&#250;mina predi&#225;lisis&#44;&#160;calcio&#44; f&#243;sforo y magnesio&#44; aunque en alg&#250;n caso se registraron valores disminuidos que no comportaron relevancia cl&#237;nica&#46;&#160;En tres pacientes la funci&#243;n renal se recuper&#243; y permanecen vivos e independientes de la di&#225;lisis&#46; En los casos biopsiados y que recuperaron funci&#243;n renal&#44; la nefropat&#237;a por cilindros fue pura&#46; Los pacientes que tardaron m&#225;s en ser diagnosticados fueron los pacientes que no recuperaron funci&#243;n renal&#44; y cuando se les efectu&#243; biopsia el diagn&#243;stico fue de nefropat&#237;a por cilindros m&#225;s enfermedad por dep&#243;sitos&#46; <span class="elsevierStyleBold">Conclusi&#243;n&#58;</span> En nuestra experiencia&#44;&#160;la hemodi&#225;lisis larga con filtros HCO es una alternativa razonable en el FRA causado por nefropat&#237;a por cilindros&#44; alcanzando en nuestros casos una tasa de recuperaci&#243;n del 50&#37;&#46; En la recuperaci&#243;n influyeron&#58; el tiempo transcurrido desde el inicio de los s&#237;ntomas al diagn&#243;stico de mieloma&#44; los hallazgos histol&#243;gicos&#44; la rapidez de instauraci&#243;n del tratamiento quimioter&#225;pico y su respuesta&#160;y&#160;la eficacia en la extracci&#243;n de cadenas ligeras&#46; En cualquier caso&#44; son necesarios nuevos estudios con nuevos agentes quimioter&#225;picos y las nuevas t&#233;cnicas&#160;de extracci&#243;n directa de cadenas ligeras&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction&#58; </span>Acute renal failure &#40;ARF&#41; occurs in 12&#37;-20&#37; of all multiple myeloma &#40;MM&#41; cases&#44; and the survival of these patients depends on renal function recovery&#46; Renal function is not recovered in 75&#37; of dialysis-dependent patients&#44; and their mean survival with replacement therapy is less than one year&#46; Renal tubular disease is the most frequent cause of renal failure&#46; It is present in more than 55&#37; of renal failure cases and in 75&#37; of those requiring dialysis&#46; Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function&#46; One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis&#44; but its efficacy has not yet been clearly proven&#46; Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers &#40;HCO-HD&#41;&#44; obtaining a recovery rate of more than 60&#37;&#46; We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis&#46; Then&#44; we review the pros and cons of this technique&#46; <span class="elsevierStyleBold">Method&#58; </span>Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500mg&#47;l were treated with 8-hour haemodialysis sessions with an HCO-HD filter&#46; Before and after each session&#44; serum free light chain levels were measured by nephelometry&#59; other parameters were recorded as well&#46; At the same time&#44; patients underwent chemotherapy according to protocols&#46; <span class="elsevierStyleBold">Results&#58; </span>The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable&#44; from 7 days to more than 1 year&#46; We performed 90 extended sessions with HCO-HD filters&#44; and each patient underwent between 6 and 40 sessions&#46; Free light chain levels decreased by a mean of 65&#37; between treatment onset and completion&#44; except in one patient who experienced a 12&#46;6&#37; reduction&#46; The mean percentage of reduction of light chain levels per session was 54&#46;98&#37;&#177;17&#46;27&#37;&#46; A complication occurred during 28&#37; of the sessions&#46; Of these complications&#44; 48&#37; were due to system coagulation&#46; There were no major changes in pre-dialysis albumin&#44; calcium&#44; phosphorous or magnesium levels&#44; although lower values that were not clinically relevant were recorded in one case&#46; Renal function was recovered in 3 patients&#44; they are alive and dialysis-free&#46; In biopsied cases that recovered renal function&#44; the specimen showed tubular nephropathy only&#46; Those patients who took longer to be diagnosed did not recover their renal function&#44; and when biopsied&#44; they were diagnosed with renal tubular disease and light chain deposition disease&#46; <span class="elsevierStyleBold">Conclusion&#58; </span>We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease&#44; and achieved a recovery rate of 50&#37; in our cases&#46; Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis&#44; histological findings&#44; promptness of starting chemotherapy&#44; response to chemotherapy&#44; and effectiveness of light chain extraction&#46; In any case&#44; further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques&#46;&#160;</p>"
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