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        "titulo" => "Tratamiento con hemodi&#225;lisis larga con filtros de alto cut-off en la nefropat&#237;a por cilindros del mieloma&#58; nuestra experiencia"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Contents</span></p><p class="elsevierStylePara">Multiple myeloma &#40;MM&#41; is a neoplastic disease consisting of clonal proliferation of the bone marrow plasma cells which produces uncontrolled amounts of immunoglobulins or their chains &#40;heavy or light&#41; that circulate in the blood as free light chains &#40;FLC&#41; and can appear in the urine &#40;Bence-Jones &#91;BJ&#93; proteinuria&#41;&#46; At an intratubular level&#44; these proteins may lead to kidney failure due to their precipitation &#40;cast nephropathy &#91;CN&#93;&#41;&#46; Light chains are medium-sized molecules with two isotypes&#58; kappa chains that are primarily monomeric in form &#40;22&#46;5kDa&#41; and lambda chains that commonly occur as dimers &#40;45 kDa&#41;&#46;</p><p class="elsevierStylePara">Myeloma represents 1&#37; of neoplasias in the Western world&#44; with an annual incidence of 5-6&#47;100&#44;000 inhabitants&#47;year&#46; Over one-third of patients are under 65 years of age&#46;<span class="elsevierStyleSup">1</span> Acute renal failure occurs in up to 50&#37; of cases of MM and is often reversible with normal treatment based on fluid and electrolyte management&#44;<span class="elsevierStyleSup">2</span> but up to 10&#37; of patients will eventually require renal replacement therapy&#46;</p><p class="elsevierStylePara">Plasma cell leukaemia is a rare variant of MM&#44;<span class="elsevierStyleSup">3</span> and constitutes 2&#37;-3&#37; of all myelomas&#46; It is a highly aggressive form of MM with poor short-term survival&#46; Plasma cell leukaemia can be classified into two subtypes&#58; 1&#46; Primary plasma cell leukaemia&#58; when there is already leukaemia development at the time of diagnosis&#46; 2&#46; Secondary plasma cell leukaemia&#58; when it appears as a result of the transformation of a previous MM&#46; Renal failure is a common result&#46;</p><p class="elsevierStylePara">The causes of renal dysfunction in patients with myeloma include impaired proximal and distal tubular function due to cell damage by filtered light chains&#44; myeloma CN&#44; amyloidosis&#44; light or heavy chain deposit disease&#44; cryoglobulinaemia&#44; interstitial infiltration by plasma cells and rarely proliferative glomerulonephritis or interstitial nephritis&#46; CN occur in 40-60&#37; of cases of myeloma associated with renal dysfunction and can cause acute renal failure&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">Thus&#44; acute renal failure is not an uncommon form of presentation for this disease and its presence will overshadow prognosis and reduce the life expectancy of the patient&#46; In recent years&#44; the introduction of new treatment strategies such as autologous bone marrow transplant and the availability of new therapeutic agents such as thalidomide&#44; lenalidomide and bortezomib have changed the management of myeloma and improved survival&#46; Other therapeutic advances that have changed the prognosis of myeloma are the introduction of apheresis techniques for the removal of light chains&#44; which reverses renal tubular damage&#46;</p><p class="elsevierStylePara">The removal of substances through the dialysis membranes depends on their molecular weight and the membrane&#8217;s pore size&#46; New generations of dialysis membranes with a cut-off close to the native kidney &#40;65 kDa&#41; can be applied in the treatment of various diseases with renal involvement&#44; including rhabdomyolysis and myeloma kidney&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">Acute kidney damage is common in patients with MM&#44; and is often caused by CN&#44; resulting from intratubular precipitation of light chains&#46; This acute kidney damage may become irreversible and usually requires treatment with dialysis&#46; The reduction of plasma FLC is associated with an improvement and sometimes recovery of renal function&#46; Plasmapheresis has been used to remove light chains&#44; with some authors finding an improvement in renal function&#44;<span class="elsevierStyleSup">4&#44;5</span> but for others its efficacy is not clear&#46;<span class="elsevierStyleSup">6</span> Recent work has shown that the removal of FLC&#44; along with chemotherapy&#44; improves survival in patients with myeloma&#46;<span class="elsevierStyleSup">7</span> Early removal is decisive in the recovery of renal function&#46;<span class="elsevierStyleSup">8</span> The method of chain removal also appears to affect recovery&#46; Thus&#44; the removal of FLC by plasmapheresis is less effective<span class="elsevierStyleSup">9</span> than when the removal is performed by long haemodialysis sessions with high cut-off filters &#40;HCO-HD&#41;&#46; This difference appears to be due primarily to the shorter duration of the plasmapheresis technique&#44; which does not allow the chains to be removed&#44; and they increase as a result of their intercompartmental redistribution&#46;<span class="elsevierStyleSup">10</span> The current high cut-off dialysers&#44; with a membrane pore size greater than 60kDa&#44; allow the removal of both the kappa and lambda chains&#46;</p><p class="elsevierStylePara">It has been demonstrated that the recovery of renal function has a positive influence on the survival of patients&#46; Similarly&#44; the type of light chain produced will have an influence on prognosis&#44; and as such&#44; the presence of kappa chains of lower molecular weight gives a better prognosis than the cases in which the lambda chain is produced&#46; The difference in the rate of removal of kappa and lambda chains seems to be most evident when using plasmapheresis&#44; whereas with long haemodialysis sessions&#44; the removal is not very different&#46; Recently&#44; haemodiafiltration techniques with ultrafiltrate reinfusion and passage through resin cartridges have begun to be used&#44; which seems to remove light chains&#44; mainly kappa&#44; effectively&#44;<span class="elsevierStyleSup">11</span> at a lower financial cost&#46; However&#44; there has not been sufficient experience with this technique in medical literature to endorse its use&#44; and as such&#44; we will have to wait for the results&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">With the current knowledge&#44; we can say that the longer the duration of the technique and the greater the area of the filter&#44; the better the FLC clearance results will be&#46; It also seems clear&#44; for most authors&#44;<span class="elsevierStyleSup">12 </span>that the removal of the aforementioned FLC&#44; either through the more effective HCO-HD technique or by plasmapheresis&#44; should be carried out at an early stage<span class="elsevierStyleSup">13</span> and be combined with a specific chemotherapy treatment to slow down the production of these anomalous chains&#46; In patients with normal renal function&#44; the use of a suitable form of chemotherapy will reduce the levels of circulating FLC to low figures&#46; Nevertheless&#44; in patients with impaired renal function&#44; FLC clearance decreases&#44; with plasma levels remaining high for a long period of time&#44; and as such toxicity is maintained at a tubular level and damage is caused that may eventually be irreversible&#44; even when the form of chemotherapy treatment is suitable&#46; Currently&#44; treatment with dexamethasone and bortezomib-based chemotherapy regimens seem to be among the most effective for treating myeloma&#46;<span class="elsevierStyleSup">14-16</span> Furthermore&#44; by using high cut-off dialysers&#44; we can accelerate the removal of FLC&#44; limiting its tubular damage in myeloma&#46;<span class="elsevierStyleSup">17&#44;18</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients&#58;</span> we present five patients&#44; two males and three females&#44; with an age range of between 51 and 68 years&#44; diagnosed with monoclonal gammopathy with very high levels of serum FLC and in all cases with acute renal failure&#46; In three of the cases&#44; the presence of light chain CN &#40;myeloma nephropathy&#41; was displayed by renal biopsy and in the two patients in whom renal biopsy could not be performed &#40;due to severe thrombocytopenia in one case and systemic antiplatelet therapy in the other&#41;&#44; the levels of light chains in urine and serum FLC were very high&#44; which along with the symptoms&#44; meant that their profile was highly suggestive of CN&#46; Four of the patients were diagnosed with MM &#40;two cases of IgG and two of IgA&#41;&#44; while in one case the diagnosis was acute plasma cell leukaemia&#46; Four patients clinically presented acute renal failure and were admitted directly to Nephrology&#46; All the cases were newly diagnosed gammopathies and all received treatment with chemotherapy simultaneously with dialysis&#46; The form of chemotherapy received is displayed in Table 1&#46;</p><p class="elsevierStylePara">In all cases&#44; treatment with hydration and correction of electrolyte imbalance was initiated prior to the diagnosis of suspected myeloma kidney&#44; without any significant improvement being obtained in any patient&#46; In four cases&#44; it was necessary to conduct acute haemodialysis due to the degree of renal failure&#44; while one patient had moderate renal failure and the technique was indicated to remove light chains&#46; The time between developing symptoms and admission varied between two and six months &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Consent&#58;</span> once informed&#44; all patients signed their specific consent for vascular access and the high cut-off filter dialysis technique&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Treatment protocol&#58;</span> HCO-HD of 6-8 hours&#58; Theralite<span class="elsevierStyleSup">&#174;</span> &#40;Gambro&#41; of 1&#46;1m<span class="elsevierStyleSup">2</span> &#40;first patient&#41; and 2m<span class="elsevierStyleSup">2</span>&#44; until achieving serum FLC figures of &#60;500mg&#47;l or recovering renal function&#44; becoming independent of dialysis&#44; for a maximum of 16 sessions&#46; During the sessions&#44; albumin supplements were administered &#40;200ml of 20&#37; albumin solution ml&#47;session&#41;&#44; phosphorus &#40;1 vial of Fosfoevac<span class="elsevierStyleSup">&#174;</span> in dialysate&#47;session&#41;&#44; magnesium &#40;1500mg&#47;session&#44; 15&#37; magnesium sulphate&#44; one vial during the last hour of dialysis&#41; and potassium &#40;20-40mEq&#47;session&#41;&#44; with subsequent adjustments in accordance with the analysis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dialysate&#58;</span> Dialsol 313-A &#40;3mEq&#47;l Ca<span class="elsevierStyleSup">&#43;&#43;</span> and 1&#46;5mEq&#47;l K<span class="elsevierStyleSup">&#43;</span>&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction of heparin into the circuit&#58;</span> initial heparin sodium of 0&#46;5mg&#47;kg plus 10mg&#47;hour&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Vascular access&#58;</span> initially&#44; a central venous catheter was temporarily placed in patients for haemodialysis&#46; Subsequently&#44; in patient 1&#44; due to progression&#44; an autologous AVF was carried out and a tunnelled catheter was placed in patient 4&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Monitoring&#58;</span> we monitored pre and post-dialysis levels of renal function&#44; calcium&#44; phosphorus&#44; magnesium&#44; potassium and albumin&#44; and we determined pre and post-dialysis FLC levels for each session&#46; In the first of the patients&#44; FLC was not able to be determined in our centre&#44; and as such&#44; it was monitored through B-J proteinuria levels in urine&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Response to treatment&#58;</span> the renal response was classified in accordance with criteria of the European Group for Blood and Marrow Transplantation&#58; 1&#41; complete response&#44; if the patient has a glomerular filtration rate &#40;GFR&#41; of &#8805;60ml&#47;min&#59; 2&#41; partial response&#44; when the GFR increases &#62;100&#37; or changes from GFR &#60;15ml&#47;min to GFR between 30-60ml&#47;min&#41;&#59; or 3&#41; minor response if the GFR increases &#62;50&#37; or changes from a rate of &#60;15 ml&#47;min to 15-30ml&#47;min or from a rate of 15-30 ml&#47;min to 30-60ml&#47;min&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">All patients received specific treatment for the haematological disease&#44; in accordance with the haematology protocol &#40;Table 1&#41;&#46; Patient 2&#44; who was diagnosed with acute primary plasma cell leukaemia&#44; received treatment with mega-CHOP and once renal function normalised and after the marrow responded to chemotherapy&#44; they underwent bone marrow transplantation with satisfactory results&#46;</p><p class="elsevierStylePara">In patients 1&#44; 3 and 5&#44; a percutaneous renal biopsy was performed&#44; showing CN in all three&#44; while in patients 2 and 4 no biopsy was carried out due to the increased risk of bleeding &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">The five patients were treated with HCO-HD for 6 hours&#46; The mean number of sessions was 12&#177;3&#46;1 &#40;8-16&#41;&#46; The first received 7 daily sessions and 9 on alternate days with 1&#46;1m<span class="elsevierStyleSup">2 </span>Theralite<span class="elsevierStyleSup">&#174;</span> filters &#40;Gambro&#41;&#44; while the other four received 5 daily sessions&#44; followed by a variable number &#40;7&#44; 3&#44; 9 and 5&#41; of sessions on alternate days with 2m<span class="elsevierStyleSup">2</span> Theralite<span class="elsevierStyleSup">&#174;</span> filters &#40;Gambro&#41;&#44; until FLC blood figures &#60;500mg&#47;l were achieved&#44; except in patient 4&#44; in whom the technique was discontinued after 14 sessions after observing stability in pre and post-dialysis FLC figures&#44; even though the desired 500mg&#47;l had not been achieved&#46; In this case&#44; given the lower chain removal efficiency&#44; we increased the duration of dialysis to 8 hours&#44; in spite of which the efficacy did not improve and given the limited effectiveness of the technique&#44; it was decided to discontinue the clearance treatment&#46; At this time&#44; renal function was stable &#40;serum creatinine of 4mg&#47;dl&#41; and levels of light chains were at 3000mg&#47;l &#40;Figure 1&#41;&#46; Once HCO-HD was discontinued&#44; FLC continued to decrease very slowly until levels below 500mg&#47;l were achieved&#44; one month later&#44; as a result of the response to myeloma treatment&#46;</p><p class="elsevierStylePara">In all patients&#44; serum FLC levels decreased during HCO-HD treatment&#44; most strikingly in the first five &#40;daily&#41; sessions&#44; at the end of which in 2 of the 4 patients&#44; FLC levels were below 1000mg&#47;l&#44; in another patient they were at 1600mg&#47;l and in patient 4&#44; the decrease was slower &#40;Figure 1&#41;&#46; In patient 1&#44; who was monitored by B-J proteinuria levels&#44; in the absence of serum FLC&#44; levels of the latter also decreased &#40;Figure 2&#41;&#46; In some patients&#44; we observed a clear interdialysis increase in FLC figures&#44; most strikingly in patient number 3&#44; while in the rest&#44; this phenomenon was more latent&#46;</p><p class="elsevierStylePara">Plasma creatinine improved in parallel with decreasing levels of FLC&#44; stabilising when levels dropped from 500 mg&#47;l in patients 2&#44; 3&#44; 4 and 5&#44; whereas in patient 1&#44; although plasma creatinine decreased as result of dialysis&#44; it remained at figures high enough to require renal replacement therapy&#46;</p><p class="elsevierStylePara">The progression of kidney function is shown in Table 2 and individually in Figure 1 and Figure 2&#46; In four of the patients &#40;patients 2&#44; 3&#44; 4 and 5&#41;&#44; renal function recovered satisfactorily&#44; allowing replacement therapy to be discontinued after completion of the treatment with HCO-HD&#46; In one case&#44; it was considered that the response was complete&#44; in another&#44; partial&#44; and in the other two&#44; minor&#46; This recovery was maintained until death in one patient&#44; and to date in the remainder &#40;26&#44; 18 and 12 months&#41;&#46;</p><p class="elsevierStylePara">We analysed the five patients individually&#58;</p><p class="elsevierStylePara">Patient 1 presented with a wide array of symptoms&#58; severe anaemia&#44; 20&#37; plasma cells in bone marrow aspiration&#44; severe renal failure &#40;serum creatinine at diagnosis of 18mg&#47;dl&#41;&#44; high monoclonal component &#40;3&#46;6g&#47;dl&#41;&#44; and when they were referred to our centre&#44; the process had progressed for at least six months&#46; Conventional haemodialysis was begun before the diagnosis was confirmed&#46; At that time&#44; we did not have FLC blood determination&#44; but on finding a very high removal of urinary light chains in urine&#44; we considered performing a renal biopsy&#44; which confirmed the diagnosis of suspected CN and the presence of a damaged tubular epithelium with mixed inflammatory infiltrate and severe interstitial fibrosis&#46; With the diagnosis of CN&#44; treatment with HCO-HD was begun with a 1&#46;1m<span class="elsevierStyleSup">2</span> filter &#40;one week after admission&#41; without the recovery of renal function being achieved&#46; Although BJ proteinuria levels decreased with HCO-HD in addition to the specific myeloma treatment &#40;vincristine&#44; doxorubicin and dexamethasone &#91;VAD&#93; plus bortezomib&#41;&#44; renal function was not recover and the patient remained in need of replacement therapy &#40;Figure 1&#41;&#59; we do not have the FLC levels of this patient due to infrastructure problems in the centre&#46; Subsequently&#44; this patient had myeloma progression and is currently receiving a new line of treatment &#40;bortezomib and adriamycin&#41; for which we are awaiting the response&#46;</p><p class="elsevierStylePara">Patient 2 was diagnosed with acute leukaemia of primary plasma cells with monoclonal lambda component and a high production and renal removal of these lambda light chains &#40;B-J proteinuria &#62;37&#44;000mg&#47;l&#41;&#44; as well as high levels of serum FLC &#40;8030mg&#47;l&#41;&#46; Since the patient was undergoing systemic antiplatelet therapy&#44; with a major risk of bleeding if a renal biopsy was performed at that time&#44; the latter was rejected in favour of establishing the histological diagnosis of CN and it was decided to start treatment with HCO-HD&#44; considering the presence in blood of high levels of lambda type FLC&#46; The response to treatment was complete&#44; with normal renal function being achieved&#46; Subsequently&#44; an autologous bone marrow transplant was performed&#44; after which normal renal function was maintained &#40;serum creatinine 0&#46;8mg&#47;dl&#41;&#44; with the absence of proteinuria&#46;</p><p class="elsevierStylePara">In patient 3&#44; the time from the beginning of symptoms until we were consulted was two months&#46; Treatment was initiated with hydration measures and there was improvement in renal function&#44; but later it worsened again&#44; showing very high FLC figures &#40;14&#44;800mg&#47;l&#41; and renal biopsy was proposed&#46; The patient displayed CN and as such&#44; it was decided to start treatment with high cut-off filter&#46; Response to treatment was favourable&#46; In this case&#44; we observed a significant recovery in serum FLC figures during the first sessions &#40;Figure 1&#41;&#46; Renal function improved&#59; after completion of treatment with HCO-HD&#44; creatinine remained stable &#40;creatinine 3mg&#47;dl&#41;&#44; and the patient became independent of dialysis&#44; although the glomerular filtration rate was around 20ml&#47;min&#46; Subsequently&#44; due to myeloma relapse&#44; it was necessary to intensify chemotherapy and as a result of this the patient developed an infectious complication that resulted in <span class="elsevierStyleItalic">exitus</span>&#46;</p><p class="elsevierStylePara">Patient 4 had a progression of at least three months of symptoms at the time of admission&#46; They had advanced renal failure and anaemia within transfusion range&#46; The bone marrow aspirate revealed the presence of 56&#37; plasma cells and the determination of serum FLC showed the presence of very high lambda FLC levels &#40;greater than 41&#44;000mg&#47;l&#41;&#46; Treatment was initiated without histological study due to haemorrhagic risk&#46; Response to treatment with HCO-HD was good&#44; with a significant decrease in the levels of light chain following the first sessions&#44; as is shown in Figure 1&#44; and levels subsequently stabilised around 3000mg&#47;l&#46; Following the discontinuation of dialysis&#44; the patient displayed a progressive reduction in serum FLC levels to values below 500mg&#47;l after one month of follow-up&#46; Renal function has remained stable until the present day and the patient is independent of dialysis&#46; From the haematological point of view&#44; despite the initial aggressiveness of symptoms&#44; the patient is currently in remission&#46;</p><p class="elsevierStylePara">Patient 5 presented renal failure symptoms&#44; with a progression of at least two months of anaemia&#46; Given the presence of high FLC levels and renal biopsy with the presence of CN&#44; we began HCO-HD&#46; Clinical response from the haematological point of view with VAD and bortezomib was good&#46; FLC reduction was parallel to the recovery of renal function&#44; which allowed the technique to be discontinued after 10 sessions with a glomerular filtration rate above 20ml&#47;min&#46; Currently&#44; almost 1&#46;5 years after diagnosis&#44; the patient is in haematological remission with creatinine levels stable at 1&#46;8mg&#47;dl&#46;</p><p class="elsevierStylePara">All patients had an excellent clinical tolerance to the technique&#46; All sessions passed with good haemodynamic stability&#46; According to the protocol&#44; they were supplemented with albumin&#44; phosphorus&#44; magnesium and potassium&#44; adjusted in accordance with the analytical controls carried out&#46; We did not observe any technical complications in the extracorporeal technique or related to vascular access&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We present five cases of monoclonal gammopathy with renal failure due to light chain nephropathy&#46; Four of them were diagnosed with MM and one with acute primary plasma cell leukaemia&#46;</p><p class="elsevierStylePara">In the case of patient 1&#44; we believe that the fact that treatment was not carried out early&#44; with six months&#39; progression of symptoms prior to renal biopsy&#44; may had an influence on progression&#44; although some authors have recently<span class="elsevierStyleSup">19</span> found improved renal function in patients with longer progression&#46; Moreover&#44; in our case we believe that the presence of tubular damage and renal interstitial fibrosis on biopsy may be the fundamental reason for the absence of renal function recovery&#46; On the other hand&#44; the filter used had a smaller surface &#40;1&#46;1m<span class="elsevierStyleSup">2</span>&#41;&#44; a fact that could have had an influence on response&#44; although due to the absence of serum FLC determination at that time&#44; we could not assess the degree of efficacy in the removal of FLC&#46; According to authors such as Hutchinson&#44; the type of light chain may influence prognosis&#44; and as such&#44; the kappa chain-producing myelomas respond better to treatment when they are monomeric forms of lower molecular weight that could be removed more easily by employing different techniques&#46;<span class="elsevierStyleSup">20</span> In patient 1&#44; the chain produced was a kappa chain and we demonstrated that its excretion in urine decreased very significantly&#44; but it is possible that kidney damage was already irreversible &#40;as expected from renal biopsy findings&#41;&#46; The patient currently remains on haemodialysis with progression of the disease and has begun a new line of chemotherapy&#46;</p><p class="elsevierStylePara">Patient 2 was diagnosed with primary plasma cell leukaemia with highly aggressive symptoms and very high FLC levels&#44; and as such he was started on treatment to remove these chains&#44; without histological confirmation&#46; Primary plasma cell<span class="elsevierStyleSup">3</span> leukaemia is characterised by its appearance in younger patients&#44; as in our case in which it appears in the youngest of the five patients&#46; The prognosis seems better than for secondary leukaemia and in our case&#44; it had the best response&#46; Bone lesions and hypercalcaemia are less common in primary plasma cell leukaemias&#44; which more commonly present organomegalies and lymphadenopathies&#46; In our patient&#44; there was hepatosplenomegaly and cutaneous infiltration&#46; There is usually a lower quantity of serum M component than in typical forms of MM&#44; which is also the case for our patient&#44; as well as the presence of renal failure&#44; which is also common&#46;</p><p class="elsevierStylePara">In this case&#44; the response to treatment was very good&#46; We did not find in literature any case of plasma cell leukaemia in which patients underwent extracorporeal clearance techniques for the removal of FLC&#46; Our patient progressed favourably&#44; recovering renal function <span class="elsevierStyleItalic">ad integrum</span>&#44; which allowed a bone marrow transplantation to be performed&#46;</p><p class="elsevierStylePara">Patient 3&#44; when we were consulted due to the presence of renal failure in a patient with a diagnosis of myeloma that was being treated&#44; already had a severe thrombocytopenia secondary to the chemotherapy treatment that they were receiving&#44; and therefore renal biopsy was not performed at that time&#44; due to haemorrhagic risk&#46; The patient initially improved on receiving medical treatment&#44; but after further deterioration of renal function&#44; and after recovery from thrombocytopenia&#44; renal biopsy was performed without complications&#46; The response to treatment with high cut-off dialysis was good&#44; with a better recovery in serum FLC figures being observed during the first four sessions&#44; which we believe to be indicative of a significant generation of FLC at the plasma cell level&#44; which still maintained high activity despite chemotherapy&#46; We observed very high serum FLC figures at the start&#44; which are also indicative of a high activity of the plasma cell clone&#46; Renal function improved&#44; and dialysis was discontinued&#44; but myeloma progressed unfavourably and <span class="elsevierStyleItalic">exitus</span> occurred due to infectious complications&#46;</p><p class="elsevierStylePara">Despite the long progression of symptoms at the time of diagnosis&#44; patient 4 responded well to treatment with HCO-HD&#44; with a significant initial decrease in background levels of light chains&#46; Subsequently&#44; we observed a stabilisation of FLC levels at around 3000mg&#47;l and found that the technique was not effective in removing the latter despite an increase in the number of hours of each session &#40;8 hours&#41;&#46; At this point and given that renal function had improved&#44; remaining at figures that did not require renal replacement therapy&#44; we decided to discontinue haemodialysis&#46; After analysing the situation&#44; we thought that the low removal efficacy could be due to the formation of lambda chain polymers with higher molecular weight and thus they were not removed by HCO-HD&#46; This phenomenon is described in literature&#44;<span class="elsevierStyleSup">21</span> although we could not demonstrate this point&#46; In this case&#44; as with patient 1&#44; there was some delay in the haematological diagnosis which we believe could have influenced the progression and non-complete recovery of renal function&#44; in light of the data we have today&#44; which tells us that the early removal of FLC is urgent in order for an improvement in the prognosis of the disease&#46;<span class="elsevierStyleSup">22</span> In this case&#44; a renal biopsy was not able to be carried out at the time of diagnosis&#44; since the patient was receiving antiplatelet treatment with aspirin&#46; The clearance technique was initiated in view of serum FLC figures and antiplatelet therapy was discontinued in order to be able to carry out biopsy after 10 days&#46; In the end&#44; it was not possible due to thrombocytopenia secondary to chemotherapy administration &#40;VAD plus bortezomib&#41;&#44; and as such&#44; given the good response to treatment&#44; it was rejected&#46; After almost two years of follow-up&#44; serum creatinine of 3&#46;6mg&#47;dl was maintained and from a haematological point of view&#44; the patient is in complete remission&#46;</p><p class="elsevierStylePara">Patient 5 had a history of at least two months of anaemia&#44; and we understand this to be at least the time of progression of the process&#46; The response to treatment was good&#44; with FLC reduction parallel to recovery of renal function as is reflected in the literature&#46;<span class="elsevierStyleSup">23</span> Once treatment was initiated on alternate days&#44; we observed some degree of recovery in interdialysis levels of FLC&#44; which eventually became negligible&#46; We believe that the shortest progression&#44; in this case&#44; could favour a good response to treatment&#46;</p><p class="elsevierStylePara">In our experience&#44; in lambda light chain-producing myeloma&#44; three of the cases generally had a good response to treatment&#44; with adequate recovery of renal function&#44; except in the case of patient 4&#44; in whom recovery was not complete&#44; which was probably due more to the duration of the disease until the beginning of HCO-HD than the anomalous chain type produced&#46; Some authors have recently have found equal efficacy in the removal of the two types of chains&#46;<span class="elsevierStyleSup">24 </span>As for the other two patients&#44; in one of those with kappa myelomas&#44; there was no response to treatment &#40;long progression period and associated interstitial renal damage&#41; and in the other we cannot establish progression&#44; given their early death after the technique was ended&#46;</p><p class="elsevierStylePara">Generally&#44; at the beginning of treatment with high cut-off filters&#44; the different authors<span class="elsevierStyleSup">8</span> were more selective in their indication and specified that evidence of CN by renal biopsy was required in order to begin the technique&#44; while authors who carried out plasmapheresis sometimes began it without histological evidence&#46;<span class="elsevierStyleSup">25</span> Over time&#44; there has been greater permissibility in this regard&#46; Some of these authors&#44; such as Hutchison&#44;<span class="elsevierStyleSup">17</span> in their latest publications performed a biopsy in less than 60&#37; of patients&#44; since&#44; as in our case&#44; sometimes it is not technically possible to do so in our clinical context&#46; On one hand&#44; this allows for earlier treatment&#44; without the requirement to wait for the histological results&#44; but on the other hand&#44; data from a biopsy can predict the prognosis<span class="elsevierStyleSup">26</span> and as such&#44; if there is only data for CN&#44; the prospect of a good progression is higher than if there is more chronic damage&#44; which would allow us to not unnecessarily prolong treatment at a high financial cost&#46; Our view is that&#44; where it is technically possible&#44; a renal biopsy should be performed&#44; with a diagnostic and prognosis purpose&#46; Given that we believe early treatment is a priority&#44; we think that&#44; once high FLC blood levels have been determined&#44; there should not be any delay in initiating the technique while waiting for the possibility of performing a renal biopsy or obtaining its result&#44; although&#44; whenever possible&#44; a renal biopsy should technically be performed&#46;</p><p class="elsevierStylePara">In some articles published recently&#44;<span class="elsevierStyleSup">27</span> the authors find complications in up to 28&#37; of the sessions&#44; many of them related to coagulation&#59; we did not have to deal with any major complications and in only one case was there a circuit coagulation&#44; forcing a filter change&#46; Neither did we have any haemorrhagic or infectious complications related to the technique or vascular access&#46; The technique was very well tolerated in all instances&#46;</p><p class="elsevierStylePara">In short&#44; we believe that the life expectancy of patients with myeloma depends on the haematological disease itself&#44; although renal involvement will modify it substantially&#46; Renal prognosis is&#44; in our experience&#44; clearly related to the progression of time until HCO-HD is started&#46; If treatment is performed early&#44; removing circulating FLC with this type of haemodialysis&#44; while decreasing the production of the latter by the plasma-cell clone&#44; the recovery of renal function&#44; albeit partial&#44; can be achieved&#44; long-term prognosis seems very positive and stability in renal function can be maintained at least in the medium term&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48077&#95;en&#95;t211932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;1&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48077_en_t211932_03_cambiado_abstract_maquetacin_1.jpg" alt="Clinical and progression data"></img></a></p><p class="elsevierStylePara">Table 2&#46; Clinical and progression data</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48078&#95;en&#95;f111932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;12&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48078_en_f111932_03_cambiado_abstract_maquetacin_12.jpg" alt="Progression of renal function and free light chains"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Progression of renal function and free light chains</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48079&#95;en&#95;f211932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;12&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48079_en_f211932_03_cambiado_abstract_maquetacin_12.jpg" alt="Progression of renal function and Bence-Jones proteinuria"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Progression of renal function and Bence-Jones proteinuria</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48082&#95;en&#95;t111932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;1&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48082_en_t111932_03_cambiado_abstract_maquetacin_1.jpg" alt="Initial epidemiological and clinical data"></img></a></p><p class="elsevierStylePara">Table 1&#46; Initial epidemiological and clinical data</p>"
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        "resumen" => "<p class="elsevierStylePara">El mieloma m&#250;ltiple &#40;MM&#41; consiste en la proliferaci&#243;n incontrolada de c&#233;lulas plasm&#225;ticas con producci&#243;n de cantidades variables de inmunoglobulinas o sus cadenas&#46; La insuficiencia renal aguda puede ser un s&#237;ntoma del MM&#44; y a veces su forma de presentaci&#243;n&#46; Las cadenas ligeras libres circulantes &#40;CLL&#41; pueden dar lugar al fallo renal por la precipitaci&#243;n intratubular de ellas&#44; causando una nefropat&#237;a por cilindros&#46; El tratamiento del mieloma&#44; una adecuada hidrataci&#243;n y la eliminaci&#243;n de CLL mediante t&#233;cnicas de af&#233;resis son los tratamientos admitidos actualmente para esta entidad&#46; Se han intentado diversas t&#233;cnicas de af&#233;resis para intentar eliminar las CLL&#44; siendo la hemodi&#225;lisis de larga duraci&#243;n con filtros para eliminar dichas cadenas ligeras &#40;alto <span class="elsevierStyleItalic">cut-off</span>&#41; la que se postula como el tratamiento m&#225;s eficaz para la nefropat&#237;a del mieloma&#46; <span class="elsevierStyleBold">M&#233;todos&#58;</span> Presentamos cinco casos de nefropat&#237;a de mieloma&#58; tres con nefropat&#237;a por cilindros &#40;NC&#41; diagnosticada por biopsia renal y dos con alta probabilidad de NC &#40;niveles de CLL &#62; 500 mg&#47;l&#41; tratados con hemodi&#225;lisis larga con membrana de alto <span class="elsevierStyleItalic">cut-off</span>&#46; Todos presentaban insuficiencia renal aguda&#44; en cuatro de ellos con necesidad de terapia sustitutiva y uno en situaci&#243;n de insuficiencia renal avanzada&#46; En todos ellos los niveles de CLL fueron muy elevados&#46; Recibieron tratamiento espec&#237;fico para el mieloma m&#225;s hemodi&#225;lisis de alto <span class="elsevierStyleItalic">cut-off</span> hasta alcanzar niveles de CLL &#60; 500 mg&#47;l&#46; <span class="elsevierStyleBold">Resultados&#58;</span> Cuatro de los cinco pacientes recuperaron funci&#243;n renal&#44; quedando independientes de di&#225;lisis&#46; El tiempo de evoluci&#243;n del mieloma desde el inicio de la cl&#237;nica fue variable &#40;1-6 m&#41;&#46; El n&#250;mero de sesiones vari&#243; entre 8-16&#46; El paciente de m&#225;s tiempo de evoluci&#243;n precis&#243; m&#225;s sesiones y no recuper&#243; funci&#243;n renal&#46; <span class="elsevierStyleBold">Conclusiones&#58;</span> La hemodi&#225;lisis larga con filtros de alto <span class="elsevierStyleItalic">cut-off</span> m&#225;s tratamiento con quimioterapia del mieloma parece ser un tratamiento eficaz en la insuficiencia renal aguda debida a nefropat&#237;a del mieloma&#46; La precocidad en el inicio del tratamiento puede ser un factor determinante de la respuesta&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleItalic">Multiple myeloma &#40;MM&#41; is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains&#46; Acute renal failure can be a symptom of MM&#44; and it is sometimes its form of presentation&#46; Circulating free light chains &#40;FLC&#41; could lead to renal failure due to their intratubular precipitation&#44; causing a cast nephropathy&#46; The treatment of myeloma&#44; adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease&#46; Several apheresis techniques have been attempted for the removal of FLC&#44; with long haemodialysis sessions with filters for the removal of these light chains &#40;high cut-off filters&#41; being proposed as the most effective treatment for myeloma nephropathy&#46; <span class="elsevierStyleBold">Methods&#58;</span> We report 5 cases of myeloma nephropathy&#58; three had cast nephropathy &#40;CN&#41; diagnosed by renal biopsy and the other two had a high probability of CN &#40;FLC levels &#62;500mg&#47;l&#41;&#46; They were treated with long haemodialysis sessions with a high cut-off membrane&#46; All patients had suffered acute renal failure&#59; four required renal replacement therapy and one patient had advanced renal failure&#46; In all patients&#44; FLC levels were very high&#46; They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of &#60;500mg&#47;l&#46; <span class="elsevierStyleBold">Results&#58;</span> Four of the five patients recovered renal function&#44; and became independent of dialysis&#46; The progression time for myeloma from the time the first symptoms appeared varied &#40;1-6 months&#41;&#46; The number of treatment sessions ranged from 8-16&#46; The patient with the longest progression time required more sessions and did not recover renal function&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy&#46; The early initiation of treatment could be a determining factor for the response&#46;</span></p>"
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Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience
Tratamiento con hemodiálisis larga con filtros de alto cut-off en la nefropatía por cilindros del mieloma: nuestra experiencia
Josefa Borrego Hinojosaa, Josefa Borrego-Hinojosab, Maria Pilar Pérez del Barrioa, M. Pilar Pérez-del Barriob, Maria del Mar Biechy Baldana, M. del Mar Biechy-Baldanb, Enoc Merino Garcíaa, Enoc Merino-Garcíab, Maria Carmen Sánchez Peralesa, M. Carmen Sánchez-Peralesb, Maria José García Cortésa, M. José García-Cortésb, Esther Ocaña Péreza, Esther Ocaña-Pérezc, Patricia Gutiérrez Rivasa, Patricia Gutiérrez-Rivasb, Antonio Liébana Cañadaa, Antonio Liébana-Cañadab
a Unidad de Nefrología, Complejo Hospitalario de Jaén, Jaén, Spain,
b Unidad de Nefrología, Complejo Hospitalario de Jaén,
c Unidad de Analisis Clínicos, Complejo Hospitalario de Jaén,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Contents</span></p><p class="elsevierStylePara">Multiple myeloma &#40;MM&#41; is a neoplastic disease consisting of clonal proliferation of the bone marrow plasma cells which produces uncontrolled amounts of immunoglobulins or their chains &#40;heavy or light&#41; that circulate in the blood as free light chains &#40;FLC&#41; and can appear in the urine &#40;Bence-Jones &#91;BJ&#93; proteinuria&#41;&#46; At an intratubular level&#44; these proteins may lead to kidney failure due to their precipitation &#40;cast nephropathy &#91;CN&#93;&#41;&#46; Light chains are medium-sized molecules with two isotypes&#58; kappa chains that are primarily monomeric in form &#40;22&#46;5kDa&#41; and lambda chains that commonly occur as dimers &#40;45 kDa&#41;&#46;</p><p class="elsevierStylePara">Myeloma represents 1&#37; of neoplasias in the Western world&#44; with an annual incidence of 5-6&#47;100&#44;000 inhabitants&#47;year&#46; Over one-third of patients are under 65 years of age&#46;<span class="elsevierStyleSup">1</span> Acute renal failure occurs in up to 50&#37; of cases of MM and is often reversible with normal treatment based on fluid and electrolyte management&#44;<span class="elsevierStyleSup">2</span> but up to 10&#37; of patients will eventually require renal replacement therapy&#46;</p><p class="elsevierStylePara">Plasma cell leukaemia is a rare variant of MM&#44;<span class="elsevierStyleSup">3</span> and constitutes 2&#37;-3&#37; of all myelomas&#46; It is a highly aggressive form of MM with poor short-term survival&#46; Plasma cell leukaemia can be classified into two subtypes&#58; 1&#46; Primary plasma cell leukaemia&#58; when there is already leukaemia development at the time of diagnosis&#46; 2&#46; Secondary plasma cell leukaemia&#58; when it appears as a result of the transformation of a previous MM&#46; Renal failure is a common result&#46;</p><p class="elsevierStylePara">The causes of renal dysfunction in patients with myeloma include impaired proximal and distal tubular function due to cell damage by filtered light chains&#44; myeloma CN&#44; amyloidosis&#44; light or heavy chain deposit disease&#44; cryoglobulinaemia&#44; interstitial infiltration by plasma cells and rarely proliferative glomerulonephritis or interstitial nephritis&#46; CN occur in 40-60&#37; of cases of myeloma associated with renal dysfunction and can cause acute renal failure&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">Thus&#44; acute renal failure is not an uncommon form of presentation for this disease and its presence will overshadow prognosis and reduce the life expectancy of the patient&#46; In recent years&#44; the introduction of new treatment strategies such as autologous bone marrow transplant and the availability of new therapeutic agents such as thalidomide&#44; lenalidomide and bortezomib have changed the management of myeloma and improved survival&#46; Other therapeutic advances that have changed the prognosis of myeloma are the introduction of apheresis techniques for the removal of light chains&#44; which reverses renal tubular damage&#46;</p><p class="elsevierStylePara">The removal of substances through the dialysis membranes depends on their molecular weight and the membrane&#8217;s pore size&#46; New generations of dialysis membranes with a cut-off close to the native kidney &#40;65 kDa&#41; can be applied in the treatment of various diseases with renal involvement&#44; including rhabdomyolysis and myeloma kidney&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">Acute kidney damage is common in patients with MM&#44; and is often caused by CN&#44; resulting from intratubular precipitation of light chains&#46; This acute kidney damage may become irreversible and usually requires treatment with dialysis&#46; The reduction of plasma FLC is associated with an improvement and sometimes recovery of renal function&#46; Plasmapheresis has been used to remove light chains&#44; with some authors finding an improvement in renal function&#44;<span class="elsevierStyleSup">4&#44;5</span> but for others its efficacy is not clear&#46;<span class="elsevierStyleSup">6</span> Recent work has shown that the removal of FLC&#44; along with chemotherapy&#44; improves survival in patients with myeloma&#46;<span class="elsevierStyleSup">7</span> Early removal is decisive in the recovery of renal function&#46;<span class="elsevierStyleSup">8</span> The method of chain removal also appears to affect recovery&#46; Thus&#44; the removal of FLC by plasmapheresis is less effective<span class="elsevierStyleSup">9</span> than when the removal is performed by long haemodialysis sessions with high cut-off filters &#40;HCO-HD&#41;&#46; This difference appears to be due primarily to the shorter duration of the plasmapheresis technique&#44; which does not allow the chains to be removed&#44; and they increase as a result of their intercompartmental redistribution&#46;<span class="elsevierStyleSup">10</span> The current high cut-off dialysers&#44; with a membrane pore size greater than 60kDa&#44; allow the removal of both the kappa and lambda chains&#46;</p><p class="elsevierStylePara">It has been demonstrated that the recovery of renal function has a positive influence on the survival of patients&#46; Similarly&#44; the type of light chain produced will have an influence on prognosis&#44; and as such&#44; the presence of kappa chains of lower molecular weight gives a better prognosis than the cases in which the lambda chain is produced&#46; The difference in the rate of removal of kappa and lambda chains seems to be most evident when using plasmapheresis&#44; whereas with long haemodialysis sessions&#44; the removal is not very different&#46; Recently&#44; haemodiafiltration techniques with ultrafiltrate reinfusion and passage through resin cartridges have begun to be used&#44; which seems to remove light chains&#44; mainly kappa&#44; effectively&#44;<span class="elsevierStyleSup">11</span> at a lower financial cost&#46; However&#44; there has not been sufficient experience with this technique in medical literature to endorse its use&#44; and as such&#44; we will have to wait for the results&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">With the current knowledge&#44; we can say that the longer the duration of the technique and the greater the area of the filter&#44; the better the FLC clearance results will be&#46; It also seems clear&#44; for most authors&#44;<span class="elsevierStyleSup">12 </span>that the removal of the aforementioned FLC&#44; either through the more effective HCO-HD technique or by plasmapheresis&#44; should be carried out at an early stage<span class="elsevierStyleSup">13</span> and be combined with a specific chemotherapy treatment to slow down the production of these anomalous chains&#46; In patients with normal renal function&#44; the use of a suitable form of chemotherapy will reduce the levels of circulating FLC to low figures&#46; Nevertheless&#44; in patients with impaired renal function&#44; FLC clearance decreases&#44; with plasma levels remaining high for a long period of time&#44; and as such toxicity is maintained at a tubular level and damage is caused that may eventually be irreversible&#44; even when the form of chemotherapy treatment is suitable&#46; Currently&#44; treatment with dexamethasone and bortezomib-based chemotherapy regimens seem to be among the most effective for treating myeloma&#46;<span class="elsevierStyleSup">14-16</span> Furthermore&#44; by using high cut-off dialysers&#44; we can accelerate the removal of FLC&#44; limiting its tubular damage in myeloma&#46;<span class="elsevierStyleSup">17&#44;18</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients&#58;</span> we present five patients&#44; two males and three females&#44; with an age range of between 51 and 68 years&#44; diagnosed with monoclonal gammopathy with very high levels of serum FLC and in all cases with acute renal failure&#46; In three of the cases&#44; the presence of light chain CN &#40;myeloma nephropathy&#41; was displayed by renal biopsy and in the two patients in whom renal biopsy could not be performed &#40;due to severe thrombocytopenia in one case and systemic antiplatelet therapy in the other&#41;&#44; the levels of light chains in urine and serum FLC were very high&#44; which along with the symptoms&#44; meant that their profile was highly suggestive of CN&#46; Four of the patients were diagnosed with MM &#40;two cases of IgG and two of IgA&#41;&#44; while in one case the diagnosis was acute plasma cell leukaemia&#46; Four patients clinically presented acute renal failure and were admitted directly to Nephrology&#46; All the cases were newly diagnosed gammopathies and all received treatment with chemotherapy simultaneously with dialysis&#46; The form of chemotherapy received is displayed in Table 1&#46;</p><p class="elsevierStylePara">In all cases&#44; treatment with hydration and correction of electrolyte imbalance was initiated prior to the diagnosis of suspected myeloma kidney&#44; without any significant improvement being obtained in any patient&#46; In four cases&#44; it was necessary to conduct acute haemodialysis due to the degree of renal failure&#44; while one patient had moderate renal failure and the technique was indicated to remove light chains&#46; The time between developing symptoms and admission varied between two and six months &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Consent&#58;</span> once informed&#44; all patients signed their specific consent for vascular access and the high cut-off filter dialysis technique&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Treatment protocol&#58;</span> HCO-HD of 6-8 hours&#58; Theralite<span class="elsevierStyleSup">&#174;</span> &#40;Gambro&#41; of 1&#46;1m<span class="elsevierStyleSup">2</span> &#40;first patient&#41; and 2m<span class="elsevierStyleSup">2</span>&#44; until achieving serum FLC figures of &#60;500mg&#47;l or recovering renal function&#44; becoming independent of dialysis&#44; for a maximum of 16 sessions&#46; During the sessions&#44; albumin supplements were administered &#40;200ml of 20&#37; albumin solution ml&#47;session&#41;&#44; phosphorus &#40;1 vial of Fosfoevac<span class="elsevierStyleSup">&#174;</span> in dialysate&#47;session&#41;&#44; magnesium &#40;1500mg&#47;session&#44; 15&#37; magnesium sulphate&#44; one vial during the last hour of dialysis&#41; and potassium &#40;20-40mEq&#47;session&#41;&#44; with subsequent adjustments in accordance with the analysis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dialysate&#58;</span> Dialsol 313-A &#40;3mEq&#47;l Ca<span class="elsevierStyleSup">&#43;&#43;</span> and 1&#46;5mEq&#47;l K<span class="elsevierStyleSup">&#43;</span>&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction of heparin into the circuit&#58;</span> initial heparin sodium of 0&#46;5mg&#47;kg plus 10mg&#47;hour&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Vascular access&#58;</span> initially&#44; a central venous catheter was temporarily placed in patients for haemodialysis&#46; Subsequently&#44; in patient 1&#44; due to progression&#44; an autologous AVF was carried out and a tunnelled catheter was placed in patient 4&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Monitoring&#58;</span> we monitored pre and post-dialysis levels of renal function&#44; calcium&#44; phosphorus&#44; magnesium&#44; potassium and albumin&#44; and we determined pre and post-dialysis FLC levels for each session&#46; In the first of the patients&#44; FLC was not able to be determined in our centre&#44; and as such&#44; it was monitored through B-J proteinuria levels in urine&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Response to treatment&#58;</span> the renal response was classified in accordance with criteria of the European Group for Blood and Marrow Transplantation&#58; 1&#41; complete response&#44; if the patient has a glomerular filtration rate &#40;GFR&#41; of &#8805;60ml&#47;min&#59; 2&#41; partial response&#44; when the GFR increases &#62;100&#37; or changes from GFR &#60;15ml&#47;min to GFR between 30-60ml&#47;min&#41;&#59; or 3&#41; minor response if the GFR increases &#62;50&#37; or changes from a rate of &#60;15 ml&#47;min to 15-30ml&#47;min or from a rate of 15-30 ml&#47;min to 30-60ml&#47;min&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">All patients received specific treatment for the haematological disease&#44; in accordance with the haematology protocol &#40;Table 1&#41;&#46; Patient 2&#44; who was diagnosed with acute primary plasma cell leukaemia&#44; received treatment with mega-CHOP and once renal function normalised and after the marrow responded to chemotherapy&#44; they underwent bone marrow transplantation with satisfactory results&#46;</p><p class="elsevierStylePara">In patients 1&#44; 3 and 5&#44; a percutaneous renal biopsy was performed&#44; showing CN in all three&#44; while in patients 2 and 4 no biopsy was carried out due to the increased risk of bleeding &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">The five patients were treated with HCO-HD for 6 hours&#46; The mean number of sessions was 12&#177;3&#46;1 &#40;8-16&#41;&#46; The first received 7 daily sessions and 9 on alternate days with 1&#46;1m<span class="elsevierStyleSup">2 </span>Theralite<span class="elsevierStyleSup">&#174;</span> filters &#40;Gambro&#41;&#44; while the other four received 5 daily sessions&#44; followed by a variable number &#40;7&#44; 3&#44; 9 and 5&#41; of sessions on alternate days with 2m<span class="elsevierStyleSup">2</span> Theralite<span class="elsevierStyleSup">&#174;</span> filters &#40;Gambro&#41;&#44; until FLC blood figures &#60;500mg&#47;l were achieved&#44; except in patient 4&#44; in whom the technique was discontinued after 14 sessions after observing stability in pre and post-dialysis FLC figures&#44; even though the desired 500mg&#47;l had not been achieved&#46; In this case&#44; given the lower chain removal efficiency&#44; we increased the duration of dialysis to 8 hours&#44; in spite of which the efficacy did not improve and given the limited effectiveness of the technique&#44; it was decided to discontinue the clearance treatment&#46; At this time&#44; renal function was stable &#40;serum creatinine of 4mg&#47;dl&#41; and levels of light chains were at 3000mg&#47;l &#40;Figure 1&#41;&#46; Once HCO-HD was discontinued&#44; FLC continued to decrease very slowly until levels below 500mg&#47;l were achieved&#44; one month later&#44; as a result of the response to myeloma treatment&#46;</p><p class="elsevierStylePara">In all patients&#44; serum FLC levels decreased during HCO-HD treatment&#44; most strikingly in the first five &#40;daily&#41; sessions&#44; at the end of which in 2 of the 4 patients&#44; FLC levels were below 1000mg&#47;l&#44; in another patient they were at 1600mg&#47;l and in patient 4&#44; the decrease was slower &#40;Figure 1&#41;&#46; In patient 1&#44; who was monitored by B-J proteinuria levels&#44; in the absence of serum FLC&#44; levels of the latter also decreased &#40;Figure 2&#41;&#46; In some patients&#44; we observed a clear interdialysis increase in FLC figures&#44; most strikingly in patient number 3&#44; while in the rest&#44; this phenomenon was more latent&#46;</p><p class="elsevierStylePara">Plasma creatinine improved in parallel with decreasing levels of FLC&#44; stabilising when levels dropped from 500 mg&#47;l in patients 2&#44; 3&#44; 4 and 5&#44; whereas in patient 1&#44; although plasma creatinine decreased as result of dialysis&#44; it remained at figures high enough to require renal replacement therapy&#46;</p><p class="elsevierStylePara">The progression of kidney function is shown in Table 2 and individually in Figure 1 and Figure 2&#46; In four of the patients &#40;patients 2&#44; 3&#44; 4 and 5&#41;&#44; renal function recovered satisfactorily&#44; allowing replacement therapy to be discontinued after completion of the treatment with HCO-HD&#46; In one case&#44; it was considered that the response was complete&#44; in another&#44; partial&#44; and in the other two&#44; minor&#46; This recovery was maintained until death in one patient&#44; and to date in the remainder &#40;26&#44; 18 and 12 months&#41;&#46;</p><p class="elsevierStylePara">We analysed the five patients individually&#58;</p><p class="elsevierStylePara">Patient 1 presented with a wide array of symptoms&#58; severe anaemia&#44; 20&#37; plasma cells in bone marrow aspiration&#44; severe renal failure &#40;serum creatinine at diagnosis of 18mg&#47;dl&#41;&#44; high monoclonal component &#40;3&#46;6g&#47;dl&#41;&#44; and when they were referred to our centre&#44; the process had progressed for at least six months&#46; Conventional haemodialysis was begun before the diagnosis was confirmed&#46; At that time&#44; we did not have FLC blood determination&#44; but on finding a very high removal of urinary light chains in urine&#44; we considered performing a renal biopsy&#44; which confirmed the diagnosis of suspected CN and the presence of a damaged tubular epithelium with mixed inflammatory infiltrate and severe interstitial fibrosis&#46; With the diagnosis of CN&#44; treatment with HCO-HD was begun with a 1&#46;1m<span class="elsevierStyleSup">2</span> filter &#40;one week after admission&#41; without the recovery of renal function being achieved&#46; Although BJ proteinuria levels decreased with HCO-HD in addition to the specific myeloma treatment &#40;vincristine&#44; doxorubicin and dexamethasone &#91;VAD&#93; plus bortezomib&#41;&#44; renal function was not recover and the patient remained in need of replacement therapy &#40;Figure 1&#41;&#59; we do not have the FLC levels of this patient due to infrastructure problems in the centre&#46; Subsequently&#44; this patient had myeloma progression and is currently receiving a new line of treatment &#40;bortezomib and adriamycin&#41; for which we are awaiting the response&#46;</p><p class="elsevierStylePara">Patient 2 was diagnosed with acute leukaemia of primary plasma cells with monoclonal lambda component and a high production and renal removal of these lambda light chains &#40;B-J proteinuria &#62;37&#44;000mg&#47;l&#41;&#44; as well as high levels of serum FLC &#40;8030mg&#47;l&#41;&#46; Since the patient was undergoing systemic antiplatelet therapy&#44; with a major risk of bleeding if a renal biopsy was performed at that time&#44; the latter was rejected in favour of establishing the histological diagnosis of CN and it was decided to start treatment with HCO-HD&#44; considering the presence in blood of high levels of lambda type FLC&#46; The response to treatment was complete&#44; with normal renal function being achieved&#46; Subsequently&#44; an autologous bone marrow transplant was performed&#44; after which normal renal function was maintained &#40;serum creatinine 0&#46;8mg&#47;dl&#41;&#44; with the absence of proteinuria&#46;</p><p class="elsevierStylePara">In patient 3&#44; the time from the beginning of symptoms until we were consulted was two months&#46; Treatment was initiated with hydration measures and there was improvement in renal function&#44; but later it worsened again&#44; showing very high FLC figures &#40;14&#44;800mg&#47;l&#41; and renal biopsy was proposed&#46; The patient displayed CN and as such&#44; it was decided to start treatment with high cut-off filter&#46; Response to treatment was favourable&#46; In this case&#44; we observed a significant recovery in serum FLC figures during the first sessions &#40;Figure 1&#41;&#46; Renal function improved&#59; after completion of treatment with HCO-HD&#44; creatinine remained stable &#40;creatinine 3mg&#47;dl&#41;&#44; and the patient became independent of dialysis&#44; although the glomerular filtration rate was around 20ml&#47;min&#46; Subsequently&#44; due to myeloma relapse&#44; it was necessary to intensify chemotherapy and as a result of this the patient developed an infectious complication that resulted in <span class="elsevierStyleItalic">exitus</span>&#46;</p><p class="elsevierStylePara">Patient 4 had a progression of at least three months of symptoms at the time of admission&#46; They had advanced renal failure and anaemia within transfusion range&#46; The bone marrow aspirate revealed the presence of 56&#37; plasma cells and the determination of serum FLC showed the presence of very high lambda FLC levels &#40;greater than 41&#44;000mg&#47;l&#41;&#46; Treatment was initiated without histological study due to haemorrhagic risk&#46; Response to treatment with HCO-HD was good&#44; with a significant decrease in the levels of light chain following the first sessions&#44; as is shown in Figure 1&#44; and levels subsequently stabilised around 3000mg&#47;l&#46; Following the discontinuation of dialysis&#44; the patient displayed a progressive reduction in serum FLC levels to values below 500mg&#47;l after one month of follow-up&#46; Renal function has remained stable until the present day and the patient is independent of dialysis&#46; From the haematological point of view&#44; despite the initial aggressiveness of symptoms&#44; the patient is currently in remission&#46;</p><p class="elsevierStylePara">Patient 5 presented renal failure symptoms&#44; with a progression of at least two months of anaemia&#46; Given the presence of high FLC levels and renal biopsy with the presence of CN&#44; we began HCO-HD&#46; Clinical response from the haematological point of view with VAD and bortezomib was good&#46; FLC reduction was parallel to the recovery of renal function&#44; which allowed the technique to be discontinued after 10 sessions with a glomerular filtration rate above 20ml&#47;min&#46; Currently&#44; almost 1&#46;5 years after diagnosis&#44; the patient is in haematological remission with creatinine levels stable at 1&#46;8mg&#47;dl&#46;</p><p class="elsevierStylePara">All patients had an excellent clinical tolerance to the technique&#46; All sessions passed with good haemodynamic stability&#46; According to the protocol&#44; they were supplemented with albumin&#44; phosphorus&#44; magnesium and potassium&#44; adjusted in accordance with the analytical controls carried out&#46; We did not observe any technical complications in the extracorporeal technique or related to vascular access&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We present five cases of monoclonal gammopathy with renal failure due to light chain nephropathy&#46; Four of them were diagnosed with MM and one with acute primary plasma cell leukaemia&#46;</p><p class="elsevierStylePara">In the case of patient 1&#44; we believe that the fact that treatment was not carried out early&#44; with six months&#39; progression of symptoms prior to renal biopsy&#44; may had an influence on progression&#44; although some authors have recently<span class="elsevierStyleSup">19</span> found improved renal function in patients with longer progression&#46; Moreover&#44; in our case we believe that the presence of tubular damage and renal interstitial fibrosis on biopsy may be the fundamental reason for the absence of renal function recovery&#46; On the other hand&#44; the filter used had a smaller surface &#40;1&#46;1m<span class="elsevierStyleSup">2</span>&#41;&#44; a fact that could have had an influence on response&#44; although due to the absence of serum FLC determination at that time&#44; we could not assess the degree of efficacy in the removal of FLC&#46; According to authors such as Hutchinson&#44; the type of light chain may influence prognosis&#44; and as such&#44; the kappa chain-producing myelomas respond better to treatment when they are monomeric forms of lower molecular weight that could be removed more easily by employing different techniques&#46;<span class="elsevierStyleSup">20</span> In patient 1&#44; the chain produced was a kappa chain and we demonstrated that its excretion in urine decreased very significantly&#44; but it is possible that kidney damage was already irreversible &#40;as expected from renal biopsy findings&#41;&#46; The patient currently remains on haemodialysis with progression of the disease and has begun a new line of chemotherapy&#46;</p><p class="elsevierStylePara">Patient 2 was diagnosed with primary plasma cell leukaemia with highly aggressive symptoms and very high FLC levels&#44; and as such he was started on treatment to remove these chains&#44; without histological confirmation&#46; Primary plasma cell<span class="elsevierStyleSup">3</span> leukaemia is characterised by its appearance in younger patients&#44; as in our case in which it appears in the youngest of the five patients&#46; The prognosis seems better than for secondary leukaemia and in our case&#44; it had the best response&#46; Bone lesions and hypercalcaemia are less common in primary plasma cell leukaemias&#44; which more commonly present organomegalies and lymphadenopathies&#46; In our patient&#44; there was hepatosplenomegaly and cutaneous infiltration&#46; There is usually a lower quantity of serum M component than in typical forms of MM&#44; which is also the case for our patient&#44; as well as the presence of renal failure&#44; which is also common&#46;</p><p class="elsevierStylePara">In this case&#44; the response to treatment was very good&#46; We did not find in literature any case of plasma cell leukaemia in which patients underwent extracorporeal clearance techniques for the removal of FLC&#46; Our patient progressed favourably&#44; recovering renal function <span class="elsevierStyleItalic">ad integrum</span>&#44; which allowed a bone marrow transplantation to be performed&#46;</p><p class="elsevierStylePara">Patient 3&#44; when we were consulted due to the presence of renal failure in a patient with a diagnosis of myeloma that was being treated&#44; already had a severe thrombocytopenia secondary to the chemotherapy treatment that they were receiving&#44; and therefore renal biopsy was not performed at that time&#44; due to haemorrhagic risk&#46; The patient initially improved on receiving medical treatment&#44; but after further deterioration of renal function&#44; and after recovery from thrombocytopenia&#44; renal biopsy was performed without complications&#46; The response to treatment with high cut-off dialysis was good&#44; with a better recovery in serum FLC figures being observed during the first four sessions&#44; which we believe to be indicative of a significant generation of FLC at the plasma cell level&#44; which still maintained high activity despite chemotherapy&#46; We observed very high serum FLC figures at the start&#44; which are also indicative of a high activity of the plasma cell clone&#46; Renal function improved&#44; and dialysis was discontinued&#44; but myeloma progressed unfavourably and <span class="elsevierStyleItalic">exitus</span> occurred due to infectious complications&#46;</p><p class="elsevierStylePara">Despite the long progression of symptoms at the time of diagnosis&#44; patient 4 responded well to treatment with HCO-HD&#44; with a significant initial decrease in background levels of light chains&#46; Subsequently&#44; we observed a stabilisation of FLC levels at around 3000mg&#47;l and found that the technique was not effective in removing the latter despite an increase in the number of hours of each session &#40;8 hours&#41;&#46; At this point and given that renal function had improved&#44; remaining at figures that did not require renal replacement therapy&#44; we decided to discontinue haemodialysis&#46; After analysing the situation&#44; we thought that the low removal efficacy could be due to the formation of lambda chain polymers with higher molecular weight and thus they were not removed by HCO-HD&#46; This phenomenon is described in literature&#44;<span class="elsevierStyleSup">21</span> although we could not demonstrate this point&#46; In this case&#44; as with patient 1&#44; there was some delay in the haematological diagnosis which we believe could have influenced the progression and non-complete recovery of renal function&#44; in light of the data we have today&#44; which tells us that the early removal of FLC is urgent in order for an improvement in the prognosis of the disease&#46;<span class="elsevierStyleSup">22</span> In this case&#44; a renal biopsy was not able to be carried out at the time of diagnosis&#44; since the patient was receiving antiplatelet treatment with aspirin&#46; The clearance technique was initiated in view of serum FLC figures and antiplatelet therapy was discontinued in order to be able to carry out biopsy after 10 days&#46; In the end&#44; it was not possible due to thrombocytopenia secondary to chemotherapy administration &#40;VAD plus bortezomib&#41;&#44; and as such&#44; given the good response to treatment&#44; it was rejected&#46; After almost two years of follow-up&#44; serum creatinine of 3&#46;6mg&#47;dl was maintained and from a haematological point of view&#44; the patient is in complete remission&#46;</p><p class="elsevierStylePara">Patient 5 had a history of at least two months of anaemia&#44; and we understand this to be at least the time of progression of the process&#46; The response to treatment was good&#44; with FLC reduction parallel to recovery of renal function as is reflected in the literature&#46;<span class="elsevierStyleSup">23</span> Once treatment was initiated on alternate days&#44; we observed some degree of recovery in interdialysis levels of FLC&#44; which eventually became negligible&#46; We believe that the shortest progression&#44; in this case&#44; could favour a good response to treatment&#46;</p><p class="elsevierStylePara">In our experience&#44; in lambda light chain-producing myeloma&#44; three of the cases generally had a good response to treatment&#44; with adequate recovery of renal function&#44; except in the case of patient 4&#44; in whom recovery was not complete&#44; which was probably due more to the duration of the disease until the beginning of HCO-HD than the anomalous chain type produced&#46; Some authors have recently have found equal efficacy in the removal of the two types of chains&#46;<span class="elsevierStyleSup">24 </span>As for the other two patients&#44; in one of those with kappa myelomas&#44; there was no response to treatment &#40;long progression period and associated interstitial renal damage&#41; and in the other we cannot establish progression&#44; given their early death after the technique was ended&#46;</p><p class="elsevierStylePara">Generally&#44; at the beginning of treatment with high cut-off filters&#44; the different authors<span class="elsevierStyleSup">8</span> were more selective in their indication and specified that evidence of CN by renal biopsy was required in order to begin the technique&#44; while authors who carried out plasmapheresis sometimes began it without histological evidence&#46;<span class="elsevierStyleSup">25</span> Over time&#44; there has been greater permissibility in this regard&#46; Some of these authors&#44; such as Hutchison&#44;<span class="elsevierStyleSup">17</span> in their latest publications performed a biopsy in less than 60&#37; of patients&#44; since&#44; as in our case&#44; sometimes it is not technically possible to do so in our clinical context&#46; On one hand&#44; this allows for earlier treatment&#44; without the requirement to wait for the histological results&#44; but on the other hand&#44; data from a biopsy can predict the prognosis<span class="elsevierStyleSup">26</span> and as such&#44; if there is only data for CN&#44; the prospect of a good progression is higher than if there is more chronic damage&#44; which would allow us to not unnecessarily prolong treatment at a high financial cost&#46; Our view is that&#44; where it is technically possible&#44; a renal biopsy should be performed&#44; with a diagnostic and prognosis purpose&#46; Given that we believe early treatment is a priority&#44; we think that&#44; once high FLC blood levels have been determined&#44; there should not be any delay in initiating the technique while waiting for the possibility of performing a renal biopsy or obtaining its result&#44; although&#44; whenever possible&#44; a renal biopsy should technically be performed&#46;</p><p class="elsevierStylePara">In some articles published recently&#44;<span class="elsevierStyleSup">27</span> the authors find complications in up to 28&#37; of the sessions&#44; many of them related to coagulation&#59; we did not have to deal with any major complications and in only one case was there a circuit coagulation&#44; forcing a filter change&#46; Neither did we have any haemorrhagic or infectious complications related to the technique or vascular access&#46; The technique was very well tolerated in all instances&#46;</p><p class="elsevierStylePara">In short&#44; we believe that the life expectancy of patients with myeloma depends on the haematological disease itself&#44; although renal involvement will modify it substantially&#46; Renal prognosis is&#44; in our experience&#44; clearly related to the progression of time until HCO-HD is started&#46; If treatment is performed early&#44; removing circulating FLC with this type of haemodialysis&#44; while decreasing the production of the latter by the plasma-cell clone&#44; the recovery of renal function&#44; albeit partial&#44; can be achieved&#44; long-term prognosis seems very positive and stability in renal function can be maintained at least in the medium term&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48077&#95;en&#95;t211932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;1&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48077_en_t211932_03_cambiado_abstract_maquetacin_1.jpg" alt="Clinical and progression data"></img></a></p><p class="elsevierStylePara">Table 2&#46; Clinical and progression data</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48078&#95;en&#95;f111932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;12&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48078_en_f111932_03_cambiado_abstract_maquetacin_12.jpg" alt="Progression of renal function and free light chains"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Progression of renal function and free light chains</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48079&#95;en&#95;f211932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;12&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48079_en_f211932_03_cambiado_abstract_maquetacin_12.jpg" alt="Progression of renal function and Bence-Jones proteinuria"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Progression of renal function and Bence-Jones proteinuria</p><p class="elsevierStylePara"><a href="grande&#47;11932&#95;16025&#95;48082&#95;en&#95;t111932&#95;03&#95;cambiado&#95;abstract&#95;maquetacin&#95;1&#46;jpg" class="elsevierStyleCrossRefs"><img src="11932_16025_48082_en_t111932_03_cambiado_abstract_maquetacin_1.jpg" alt="Initial epidemiological and clinical data"></img></a></p><p class="elsevierStylePara">Table 1&#46; Initial epidemiological and clinical data</p>"
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        "resumen" => "<p class="elsevierStylePara">El mieloma m&#250;ltiple &#40;MM&#41; consiste en la proliferaci&#243;n incontrolada de c&#233;lulas plasm&#225;ticas con producci&#243;n de cantidades variables de inmunoglobulinas o sus cadenas&#46; La insuficiencia renal aguda puede ser un s&#237;ntoma del MM&#44; y a veces su forma de presentaci&#243;n&#46; Las cadenas ligeras libres circulantes &#40;CLL&#41; pueden dar lugar al fallo renal por la precipitaci&#243;n intratubular de ellas&#44; causando una nefropat&#237;a por cilindros&#46; El tratamiento del mieloma&#44; una adecuada hidrataci&#243;n y la eliminaci&#243;n de CLL mediante t&#233;cnicas de af&#233;resis son los tratamientos admitidos actualmente para esta entidad&#46; Se han intentado diversas t&#233;cnicas de af&#233;resis para intentar eliminar las CLL&#44; siendo la hemodi&#225;lisis de larga duraci&#243;n con filtros para eliminar dichas cadenas ligeras &#40;alto <span class="elsevierStyleItalic">cut-off</span>&#41; la que se postula como el tratamiento m&#225;s eficaz para la nefropat&#237;a del mieloma&#46; <span class="elsevierStyleBold">M&#233;todos&#58;</span> Presentamos cinco casos de nefropat&#237;a de mieloma&#58; tres con nefropat&#237;a por cilindros &#40;NC&#41; diagnosticada por biopsia renal y dos con alta probabilidad de NC &#40;niveles de CLL &#62; 500 mg&#47;l&#41; tratados con hemodi&#225;lisis larga con membrana de alto <span class="elsevierStyleItalic">cut-off</span>&#46; Todos presentaban insuficiencia renal aguda&#44; en cuatro de ellos con necesidad de terapia sustitutiva y uno en situaci&#243;n de insuficiencia renal avanzada&#46; En todos ellos los niveles de CLL fueron muy elevados&#46; Recibieron tratamiento espec&#237;fico para el mieloma m&#225;s hemodi&#225;lisis de alto <span class="elsevierStyleItalic">cut-off</span> hasta alcanzar niveles de CLL &#60; 500 mg&#47;l&#46; <span class="elsevierStyleBold">Resultados&#58;</span> Cuatro de los cinco pacientes recuperaron funci&#243;n renal&#44; quedando independientes de di&#225;lisis&#46; El tiempo de evoluci&#243;n del mieloma desde el inicio de la cl&#237;nica fue variable &#40;1-6 m&#41;&#46; El n&#250;mero de sesiones vari&#243; entre 8-16&#46; El paciente de m&#225;s tiempo de evoluci&#243;n precis&#243; m&#225;s sesiones y no recuper&#243; funci&#243;n renal&#46; <span class="elsevierStyleBold">Conclusiones&#58;</span> La hemodi&#225;lisis larga con filtros de alto <span class="elsevierStyleItalic">cut-off</span> m&#225;s tratamiento con quimioterapia del mieloma parece ser un tratamiento eficaz en la insuficiencia renal aguda debida a nefropat&#237;a del mieloma&#46; La precocidad en el inicio del tratamiento puede ser un factor determinante de la respuesta&#46;</p>"
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      "en" => array:1 [
        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleItalic">Multiple myeloma &#40;MM&#41; is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains&#46; Acute renal failure can be a symptom of MM&#44; and it is sometimes its form of presentation&#46; Circulating free light chains &#40;FLC&#41; could lead to renal failure due to their intratubular precipitation&#44; causing a cast nephropathy&#46; The treatment of myeloma&#44; adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease&#46; Several apheresis techniques have been attempted for the removal of FLC&#44; with long haemodialysis sessions with filters for the removal of these light chains &#40;high cut-off filters&#41; being proposed as the most effective treatment for myeloma nephropathy&#46; <span class="elsevierStyleBold">Methods&#58;</span> We report 5 cases of myeloma nephropathy&#58; three had cast nephropathy &#40;CN&#41; diagnosed by renal biopsy and the other two had a high probability of CN &#40;FLC levels &#62;500mg&#47;l&#41;&#46; They were treated with long haemodialysis sessions with a high cut-off membrane&#46; All patients had suffered acute renal failure&#59; four required renal replacement therapy and one patient had advanced renal failure&#46; In all patients&#44; FLC levels were very high&#46; They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of &#60;500mg&#47;l&#46; <span class="elsevierStyleBold">Results&#58;</span> Four of the five patients recovered renal function&#44; and became independent of dialysis&#46; The progression time for myeloma from the time the first symptoms appeared varied &#40;1-6 months&#41;&#46; The number of treatment sessions ranged from 8-16&#46; The patient with the longest progression time required more sessions and did not recover renal function&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy&#46; The early initiation of treatment could be a determining factor for the response&#46;</span></p>"
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                  "referenciaCompleta" => "Cockwell P, Cook M. The rationale and evidence base for the direct removal of serum-free light chains in the management of myeloma kidney. Adv Chronic Kidney Dis 2012;19(5):324-32. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22920643" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
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Article information
ISSN: 20132514
Original language: English
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