Acute renal failure associated with Pemetrexed (Alimta®)
Fracaso renal agudo asociado a Pemetrexed (Alimta®)
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"apellidos" => "Florián Jericó" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología, Hospital de Barbastro, Barbastro, Huesca, España, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario Arnau de Vilanova, Lérida, España, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Unidad de Oncología Médica, Hospital de Barbastro, Barbastro, Huesca, España, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fracaso renal agudo asociado a Pemetrexed (Alimta®)" ] ] "textoCompleto" => "<p class="elsevierStylePara">Dear Editor,</p><p class="elsevierStylePara">Pemetrexed disodium (Alimta®, Eli Lilly) is a chemotherapy agent belonging to the antifolates class and it is approved for the treatment of patients with mesothelioma and non-small cell lung cancer. It is almost exclusively excreted by kidneys and, although very sporadic, some acute renal failure cases have been reported associated with its use, such as the one described as follows:</p><p class="elsevierStylePara">A 56-year-old male patient with a medical history of smoking 40 cigarettes per day, and having worked in coal mines for 16 years. He met the criteria for chronic bronchitis and suffered from osteoarthritis. In March 2008 he was diagnosed with stage IV adenocarcinoma of the lung (bilateral pulmonary nodules), following the accidental discovery of a pulmonary mass in a chest X-ray. He received treatment with carboplatin and taxol between April and September 2008, with good tolerance and mid-term response to CT scan. The patient¿s check-ups showed no complications until December 2008, when the progression of the pulmonary lesions was discovered. This is why a treatment of Pemetrexed was administered at a dose of 500mg/m<span class="elsevierStyleSup">2</span>(953mg) by means of IV every 3 weeks, together with folic acid and Vitamin B12 supplements. The patient received the first five cycles with no complications. The serum creatinine in the first cycle was 0.76mg/dl, similar to the following two; in the fourth it was 1.1mg/dl and in the fifth 1.6mg/dl (glomerular filtration rate estimated with MDRD-IDMS at 44.9ml/min/1.73m).<span class="elsevierStyleSup">2</span> Pemetrexed was not administered in the sixth cycle due to severe anaemia (24% haematocrit) with no signs of haemorrhage and with normal leukocytes and platelets, as well as non-oliguric acute renal failure with a serum creatinine of 5.2mg/dl. The patient was hospitalised in order to be tested and treated. A month and a half beforehand, he had received IV contrast to perform a CT scan. During re-examination, the patient also mentioned that for several months he was taking three daily doses of 600 milligrams of ibuprofen as a treatment for osteoarthritis pain. An abdominal ultrasound revealed the presence of a possible hepatic metastasis of 2.1cm in the left hepatic lobe; the kidneys and the prostate were of normal size and there was no hydronephrosis. The 24-hour protein excretion in the urine was 112mg. A conservative medical treatment was chosen with blood transfusion, parenteral hydratation and diuretics. The patient had an adequate diuresis at all times without signs of hydroelectrolitic imbalance. This is why there were no plans for a haemodialysis. There was a gradual yet slow recovery of the renal function. The patient was discharged after 2 weeks to continue with oncology tests. Two months later, the serum creatinine was 3.3mg/dl without any further complications.</p><p class="elsevierStylePara">The technical record of the medicine shows that in clinical studies patients with a creatinine clearance of > 45ml/min do not require dose adjustments different from those recommended for all patients. There are no sufficient data on the use of Pemetrexed in patients with creatinine clearance.<span class="elsevierStyleSup">1</span> In our patient, the analysis coinciding with the fifth cycle of Pemetrexed was truly within this limit. The technical record also underscores that the concomitant use of non-steroidal anti-inflammatory drugs should be avoided. In our case it went undetected and they could have contributed to the appearance of acute renal failure. The IV contrast administered 2 weeks after the fifth cycle could have also contributed to the initial deterioration of the renal function. Nonetheless, the chronological sequence of the clinical data makes us consider Pemetrexed as the main cause. This medicine is excreted in an unaltered way almost exclusively through the urine (70-90%). It does not undergo metabolism and it can be found in 81% of the plasma proteins. Its plasma clearance decreases in the presence of an altered glomerular filtration rate. In patients with normal renal function, its half-life is 3 hours,<span class="elsevierStyleSup">2 </span>and there are reports of its accumulation in ascitic fluid.<span class="elsevierStyleSup">3</span> There are reports of all types of renal failure in 2.4% of the patients during phase III clinical tests.<span class="elsevierStyleSup">2</span> In cases previously published, the reason for renal failure was attributed to a toxic acute tubular necrosis, although no kidney biopsies have been reported in any of the patients. Some patients fully recover,<span class="elsevierStyleSup">4,5</span> while others need chronic dialysis.<span class="elsevierStyleSup">3</span> Also in one case, there were reports of the induction of nephrogenic diabetes insipidus together with renal tubular acidosis through three treatment cycles.<span class="elsevierStyleSup">4</span> Concerning therapeutic management, it is not clear which method is the most effective to reduce the toxic levels of the drug in the context of an overdose or a renal failure. Continuous venovenous dialysis does not appear to reduce large amounts of the drug, and it is unknown if other types of dialysis can improve its clearance. There are positive preliminary reports on the use of thymidine5 and of leucovorin<span class="elsevierStyleSup">3</span> as antidotes. Another agent with possible beneficial effects is carboxypeptidase G2; however, it is necessary to gain more clinical experience on this agent, as well as on thymidine and leucovorin.<span class="elsevierStyleSup">3</span></p><p class="elsevierStylePara">In short, we report a new case of acute renal failure associated with Pemetrexed. It is necessary to emphasise the need to scrupulously respect this drug¿s technical specifications, as well as those of other chemotherapy agents which also have a wide therapeutic range, to minimise the risk of possible side effects. Another challenge is the treatment of cancer patients with organic dysfunctions, such as renal failure, with a dose of chemotherapy drugs that are as safe as those administered to patients without such dysfunctions.<span class="elsevierStyleSup">6</span></p>" "pdfFichero" => "P-E-S-A455-EN.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Mita AC, Sweeney CJ, Baker SD, Goetz A, Hammond LA, Patnaik A, et al. Phase I and pharmacokinetic study of Pemetrexed administered every 3 weeks to advanced cancer patients with normal and impaired renal function. J Clin Oncol 2006;24:552-62. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16391300" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hazarika M, White RM, Johnson JR, Pazdur R. FDA drug approval summaries: Pemetrexed (Alimta®). Oncologist 2004;9:482-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15477632" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Brandes JC, Grossman SA, Ahmad H. Alteration of Pemetrexed excretion in the presence of acute renal failure and effusions: presentation of a case and review" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "of the literature. Cancer Invest 2006; 24:283-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16809156" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Vootukuru V, Ping Y, Nally JV. Pemetrexedinduced acute renal failure, nephrogenic diabetes insipidus, and renal tubular acidosis in a patient with non-small cell lung cancer. Med Oncol 2006;23:419-22. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17018900" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Castro M. Thymidine rescue: an antidote for pemetexed-related toxicity in the setting of acute renal failure. J Clin Oncol 2003;21:4066. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14581433" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Arman A, White RM. Cytotoxic anticancer agents and renal impairement study: the challenge remains. J Clin Oncol 2006;24:533-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16391294" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000002900000006/v0_201502091611/X2013251409033626/v0_201502091612/en/main.assets" "Apartado" => array:4 [ "identificador" => "35436" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000002900000006/v0_201502091611/X2013251409033626/v0_201502091612/en/P-E-S-A455-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251409033626?idApp=UINPBA000064" ]
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| 2016 May | 130 | 0 | 130 |
| 2016 April | 85 | 0 | 85 |
| 2016 March | 68 | 0 | 68 |
| 2016 February | 76 | 0 | 76 |
| 2016 January | 98 | 0 | 98 |
| 2015 December | 90 | 0 | 90 |
| 2015 November | 86 | 0 | 86 |
| 2015 October | 75 | 0 | 75 |
| 2015 September | 55 | 0 | 55 |
| 2015 August | 56 | 0 | 56 |
| 2015 July | 60 | 0 | 60 |
| 2015 June | 36 | 0 | 36 |
| 2015 May | 51 | 0 | 51 |
| 2015 April | 6 | 0 | 6 |
Show all
