Medical therapy with tranexamic acid in autosomal dominant polycystic kidney disease patients with severe haematuria
Tratamiento con ácido tranexámico de la hematuria incoercible en la poliquistosis renal autosómica dominante
Read
13033
Timeswas read the article
3937
Total PDF
9096
Total HTML
Share statistics
array:21 [ "pii" => "X2013251412000965" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2011.Dec.11210" "estado" => "S300" "fechaPublicacion" => "2012-03-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2012;32:160-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6555 "formatos" => array:3 [ "EPUB" => 303 "HTML" => 5224 "PDF" => 1028 ] ] "Traduccion" => array:1 [ "es" => array:17 [ "pii" => "X0211699512000968" "issn" => "02116995" "doi" => "10.3265/Nefrologia.pre2011.Dec.11210" "estado" => "S300" "fechaPublicacion" => "2012-03-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2012;32:160-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 21491 "formatos" => array:3 [ "EPUB" => 304 "HTML" => 20384 "PDF" => 803 ] ] "es" => array:12 [ "idiomaDefecto" => true "titulo" => "Tratamiento con ácido tranexámico de la hematuria incoercible en la poliquistosis renal autosómica dominante" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "160" "paginaFinal" => "165" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Medical therapy with tranexamic acid in autosomal dominant polycystic kidney disease patients with severe haematuria" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11210_108_22499_es_11210_f1.jpg" "Alto" => 595 "Ancho" => 497 "Tamanyo" => 116990 ] ] "descripcion" => array:1 [ "es" => "Resonancia magnética del caso 6 mostrando numerosos quistes renales con signos de sangrado intraquístico y niveles líquido-líquido" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ramón Peces, Ana Aguilar, Cristina Vega, Emilio Cuesta, Carlos Peces, Rafael Selgas" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Ramón" "apellidos" => "Peces" ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Aguilar" ] 2 => array:2 [ "nombre" => "Cristina" "apellidos" => "Vega" ] 3 => array:2 [ "nombre" => "Emilio" "apellidos" => "Cuesta" ] 4 => array:2 [ "nombre" => "Carlos" "apellidos" => "Peces" ] 5 => array:2 [ "nombre" => "Rafael" "apellidos" => "Selgas" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X2013251412000965" "doi" => "10.3265/Nefrologia.pre2011.Dec.11210" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000965?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699512000968?idApp=UINPBA000064" "url" => "/02116995/0000003200000002/v0_201502091353/X0211699512000968/v0_201502091353/es/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "X2013251412000957" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2011.Dec.11194" "estado" => "S300" "fechaPublicacion" => "2012-03-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2012;32:166-71" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 12368 "formatos" => array:3 [ "EPUB" => 300 "HTML" => 10999 "PDF" => 1069 ] ] "en" => array:12 [ "idiomaDefecto" => true "titulo" => "Recovery of renal function in patients receiving haemodialysis treatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "166" "paginaFinal" => "171" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recuperación de la función renal en enfermos tratados con hemodiálisis" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11194_16025_27946_en_t1_11194i_copia.jpg" "Alto" => 1322 "Ancho" => 1067 "Tamanyo" => 930838 ] ] "descripcion" => array:1 [ "en" => "Baseline values for the study population" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Milagros Fernández Lucas, Milagros Fernández-Lucas, José Luis Teruel Briones, José L. Teruel-Briones, Antonio Gomis, Jhon Fernández Rodriguez, Jhon Fernández-Rodríguez, Gloria Ruiz Roso, Gloria Ruiz-Roso, Franz Fernández Rodriguez, Franz Fernández-Rodríguez, Carlos Quereda" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Milagros" "apellidos" => "Fernández Lucas" ] 1 => array:2 [ "nombre" => "Milagros" "apellidos" => "Fernández-Lucas" ] 2 => array:2 [ "nombre" => "José Luis" "apellidos" => "Teruel Briones" ] 3 => array:2 [ "nombre" => "José L." "apellidos" => "Teruel-Briones" ] 4 => array:2 [ "nombre" => "Antonio" "apellidos" => "Gomis" ] 5 => array:2 [ "nombre" => "Jhon" "apellidos" => "Fernández Rodriguez" ] 6 => array:2 [ "nombre" => "Jhon" "apellidos" => "Fernández-Rodríguez" ] 7 => array:2 [ "nombre" => "Gloria" "apellidos" => "Ruiz Roso" ] 8 => array:2 [ "nombre" => "Gloria" "apellidos" => "Ruiz-Roso" ] 9 => array:2 [ "nombre" => "Franz" "apellidos" => "Fernández Rodriguez" ] 10 => array:2 [ "nombre" => "Franz" "apellidos" => "Fernández-Rodríguez" ] 11 => array:2 [ "nombre" => "Carlos" "apellidos" => "Quereda" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X021169951200095X" "doi" => "10.3265/Nefrologia.pre2011.Dec.11194" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X021169951200095X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000957?idApp=UINPBA000064" "url" => "/20132514/0000003200000002/v0_201502091616/X2013251412000957/v0_201502091616/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "X2013251412000973" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2011.Dec.10663" "estado" => "S300" "fechaPublicacion" => "2012-03-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2012;32:153-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4335 "formatos" => array:3 [ "EPUB" => 279 "HTML" => 3380 "PDF" => 676 ] ] "en" => array:12 [ "idiomaDefecto" => true "titulo" => "Association of C49620T ABCC8 polymorphism with anthropometric and metabolic parameters in patients with autosomal dominant polycystic kidney disease: a preliminary study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "153" "paginaFinal" => "159" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asociación del polimorfismo C49620T ABCC8 con parámetros antropométricos y metabólicos en pacientes con enfermedad poliquística renal autosómica dominante: un estudio preliminar" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10663_108_25911_en_10663_t1.jpg" "Alto" => 360 "Ancho" => 600 "Tamanyo" => 259853 ] ] "descripcion" => array:1 [ "en" => "Associations between C49620T (rs1799854) variants of the ABCC8 gene and anthropometric and biochemical parameters among ADPKD and control groups" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Maria Pietrzak-Nowacka, Krzysztof Safranow, Agnieszka Binczak-Kuleta, Jacek Rozanski, Kazimierz Ciechanowski, Andrzej Ciechanowicz" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Maria" "apellidos" => "Pietrzak-Nowacka" ] 1 => array:2 [ "nombre" => "Krzysztof" "apellidos" => "Safranow" ] 2 => array:2 [ "nombre" => "Agnieszka" "apellidos" => "Binczak-Kuleta" ] 3 => array:2 [ "nombre" => "Jacek" "apellidos" => "Rozanski" ] 4 => array:2 [ "nombre" => "Kazimierz" "apellidos" => "Ciechanowski" ] 5 => array:2 [ "nombre" => "Andrzej" "apellidos" => "Ciechanowicz" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X0211699512000976" "doi" => "10.3265/Nefrologia.pre2011.Dec.10663" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699512000976?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000973?idApp=UINPBA000064" "url" => "/20132514/0000003200000002/v0_201502091616/X2013251412000973/v0_201502091616/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "titulo" => "Medical therapy with tranexamic acid in autosomal dominant polycystic kidney disease patients with severe haematuria" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "160" "paginaFinal" => "165" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Ramón Peces, Ana Aguilar, Cristina Vega, Emilio Cuesta, Carlos Peces, Rafael Selgas" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Ramón" "apellidos" => "Peces" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "Ana" "apellidos" => "Aguilar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "nombre" => "Cristina" "apellidos" => "Vega" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Emilio" "apellidos" => "Cuesta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 4 => array:3 [ "nombre" => "Carlos" "apellidos" => "Peces" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] 5 => array:3 [ "nombre" => "Rafael" "apellidos" => "Selgas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario La Paz. IdiPAZ, Madrid, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Radiología, Hospital Universitario La Paz. IdiPAZ, Madrid, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Área de Tecnología de la Información, SESCAM, Toledo, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento con ácido tranexámico de la hematuria incoercible en la poliquistosis renal autosómica dominante" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11210_16025_27914_en_t1_11210i.jpg" "Alto" => 1146 "Ancho" => 2225 "Tamanyo" => 1192021 ] ] "descripcion" => array:1 [ "en" => "Clinical data from ADPKD patients before and after medical therapy with tranexamic acid" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Haematuria is a common problem in autosomal dominant polycystic kidney disease, more than 60% of patients experiencing at least one episode of gross haematuria.<span class="elsevierStyleSup">1-4</span> These episodes are normally managed with conservative medical treatment and rarely require surgery. Although they are self-limiting, successive episodes of gross haematuria may have a detrimental effect on renal function in the long term.<span class="elsevierStyleSup">3,4</span> On the other hand, imaging techniques such as magnetic resonance (MRI) and computed tomography (CT) have become widespread, and we may now observe intracystic haemorrhages that would never have been noticed before. This is an important step forward, since it is widely known that patients with ADPKD who suffer from frequent haematuria episodes or show signs of intracystic haemorrhage develop chronic renal failure (CRF) more quickly.<span class="elsevierStyleSup">5,6</span> Conservative treatment for haematuria in ADPKD involves bed rest, blood transfusion, IV fluid, correcting blood disorders and use of vasopressin and erythropoiesis-stimulating factors. At present, there is no effective medical therapy for patients with intractable haematuria<span class="elsevierStyleSup">7</span> other than invasive procedures such as embolisation or nephrectomy. Nevertheless, other treatment methods have been tested with the aim of preserving renal function and avoiding long hospital stays, embolisation, and nephrectomy. These methods include the use of antifibrinolytics such as aprotinin and epsilon-aminocaproic acid,<span class="elsevierStyleSup">8</span> and more recently, tranexamic acid.<span class="elsevierStyleSup">9,10</span></p><p class="elsevierStylePara">Tranexamic acid is a synthetic lysine analogue with strong anti-fibrinolytic activity. It is commonly used to treat a number of bleeding disorders, including CRF.<span class="elsevierStyleSup">11-16</span> Several studies have shown it to reduce blood loss in patients with primary menorrhagia and those who have undergone cardiopulmonary bypass surgery, prostatectomy, hip replacement, and liver transplant procedures.<span class="elsevierStyleSup">17</span> However, we have not yet determined the effect of low doses of tranexamic acid on managing cyst bleeding and on renal function in ADPKD patients with a relatively preserved renal function or at a certain stage of CRF. In addition, since systemic and local hyperfibrinolysis may play a role in cyst bleeding in ADPKD,<span class="elsevierStyleSup">13</span> tranexamic acid was administered to a cohort of patients with different levels of renal function and intractable haematuria that did not respond to conventional treatment.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND RESULTS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">An observational study was conducted between 2009 and 2011 that included 8 patients with ADPKD (5 men and 3 women aged 23-51 years) who were referred to us due to intractable haematuria and suspected cyst bleeding, and who received treatment with tranexamic acid (Amchafibrin<span class="elsevierStyleSup">®</span>, Rottapharm, Spain). In all cases, ultrasound (US), CT and/or MR imaging were used for diagnosis and follow-up. Medical histories and imaging studies were reviewed in order to determine the cause of the cyst bleeding. All patients showed a very high total renal volume measured by manual segmentation, and MRI and CT images showed several cysts with signs of intracystic haemorrhage.<span class="elsevierStyleBold"> </span>Case 4 was administered initial treatment with 4 doses of recombinant Factor VII (Novoseven<span class="elsevierStyleSup">®</span>, Novo Nordisk, Spain), which was ineffective. Case 5 was also diagnosed with sickle-cell anaemia and had a history of recurrent haematuria. Three of the 8 patients were treated with IV tranexamic acid, hydration therapy, analgesics and blood transfusions. They were discharged 1 or 2 days after haematuria stopped and haemoglobin levels stabilised. The other 5 patients were treated with oral tranexamic acid on an outpatient basis. In all cases, haematuria resolved immediately or within a few days; haemoglobin levels and renal function remained stable. No thromboembolic or other complications were observed. There were no new haematuria episodes in the 3 months following discharge.</p><p class="elsevierStylePara">Table 1 provides a summary of the clinical and evolution data of the 8 patients treated with tranexamic acid. Figure 1 shows an example of renal cysts with signs of intracystic haemorrhage.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Gross haematuria caused by the rupture of renal cysts is a common manifestation of ADPKD. Haematuria is the first sign of the disease in 35% of all cases, and either gross or microscopic haematuria is detected in 60% of this patient population.<span class="elsevierStyleSup">1-6</span> Risk of haematuria seems to be associated with the presence of hypertension and cyst size increase. Although most patients report trauma or strenuous exercise as possible triggers, a precise association has never been proven between such triggering mechanisms and the condition. While polycystic kidneys are quite resistant to traumatic damage, mild trauma<span class="elsevierStyleSup">18-20</span> may give rise to intrarenal or retroperitoneal bleeding, accompanied by intense pain which may require administration of narcotics.<span class="elsevierStyleSup">21,22</span> Cysts are associated with excessive angiogenesis evinced by fragile vessels stretched across their distended walls.<span class="elsevierStyleSup">23,24</span> These vessels present an array of malformations, including aneurysms and spiral shapes. These vessels may leak blood into the cyst, either spontaneously or due to trauma; and as a result, the cyst will expand rapidly, causing intense pain. If bleeding continues, the cyst may rupture into the collecting system, which causes gross haematuria. Another possibility is that the cyst will break into the subcapsular compartment and eventually dissect through the renal capsule to fill the retroperitoneal space. In the case of massive bleeding, blood may reach the skin covering the flank and abdomen, manifested as subcutaneous ecchymosis (Grey Turner's sign). Intracystic haemorrhages in the kidney may be diagnosed by using US, CT or MRI. However, diagnosis is difficult in the presence of a persistent, but very slight<span class="elsevierStyleBold"> </span>haemorrhage. On the other hand, positron emission tomography-CT allows us to distinguish haemorrhages from cystic infection.<span class="elsevierStyleSup">25-27</span> Evidence from CT scans suggests that intracystic haemorrhage, shown as hyperdense subcapsular cysts, is present in 90% of patients with ADPKD.<span class="elsevierStyleSup">28,29</span> There are often dozens of superficial cysts that may cause intracystic haemorrhage. Direct inspection of the “hyperdense” cysts has revealed them to be filled with cellular debris derived from the breakdown of blood products.</p><p class="elsevierStylePara">Patients with a history of renal haemorrhage, as demonstrated by repeated episodes of gross haematuria, have larger kidneys<span class="elsevierStyleSup">1-6</span> and develop renal failure sooner than patients with no history of renal haemorrhage. In a retrospective study, Gabow et al<span class="elsevierStyleSup">1,2</span> found that male athletes with ADPKD who participated in contact sports had more haematuria episodes and developed kidney failure faster than those who did not participate in such sports. Renal haemorrhage caused by ruptured cysts may occur in patients of all ages, and this decreases their quality of life. There is currently no medical treatment for ADPKD patients with severe intractable haemorrhage, apart from conservative treatment and the use of invasive procedures such as embolisation and/or nephrectomy.</p><p class="elsevierStylePara">Tranexamic acid (trans-4-(aminomethyl)cyclohexanecarboxylic acid) is commonly used for the treatment of a number of bleeding disorders<span class="elsevierStyleItalic">.</span><span class="elsevierStyleSup">11-16</span> It is a synthetic lysine analogue with strong anti-fibrinolytic activity. The plasminogen binds to fibrin to form plasmin, which in turn breaks down fibrin molecules into fibrin degradation products. Tranexamic acid blocks plasminogen's lysine binding sites and prevents its interaction with fibrin. As a fibrinolysis inhibitor, it is 7 to 10 times more potent than epsilon aminocaproic acid. Some clinical trials have proven it to reduce blood loss in patients with primary menorrhagia and those who have undergone cardiopulmonary bypass surgery, prostatectomy, hip replacement and liver transplant procedures.<span class="elsevierStyleSup">17</span> It was recently reported to be effective in treating haematuria in patients with sickle-cell anaemia as well.<span class="elsevierStyleSup">30</span> Tranexamic acid is well-tolerated in general. Although a few cases of renal cortical necrosis have been reported,<span class="elsevierStyleSup">31,32</span> its side effects are mainly gastrointestinal and include nausea, vomiting, diarrhoea and abdominal pain. Myoclonus and encephalopathy due to overdose have been described in only one case.<span class="elsevierStyleSup">33</span> Tranexamic acid is excreted through glomerular filtration, and therefore accumulates in the presence of low renal function. Patients with CRF will require dose titration. On the other hand, the effectiveness of haemodialysis in tranexamic acid elimination has not been studied.<span class="elsevierStyleSup">15,16</span> The normal dose is 10mg/kg given 3 or 4 times daily. Andersson et al<span class="elsevierStyleSup">34</span> recommend reducing dosages in patients with decreased renal function as follows: for serum creatinine levels of 120-250µmol/l (1.36-2.83mg/dl), 10mg/kg IV twice daily; for serum creatinine levels of 250-500µmol/l (2.83-5.66mg/dl), 10mg/kg IV once daily; for serum creatinine levels ≥500µmol/l (5.66 mg/dl), 10mg/kg IV every 48 hours. Similar doses have been used with good results in patients on dialysis with upper digestive tract haemorrhage.<span class="elsevierStyleSup">16</span></p><p class="elsevierStylePara">Treatment options for controlling severe haemorrhage from polycystic kidneys are limited.<span class="elsevierStyleSup">35-39</span> As far as we are aware, there have been only two published studies of tranexamic acid as treatment for haematuria due to cyst bleeding in ADPKD, and both were isolated cases.<span class="elsevierStyleSup">9,10</span> In one of the cases, the initial dose was 20mg/kg IV, which was later maintained by the oral route.<span class="elsevierStyleSup">9</span> In the other case, which was treated with tranexamic acid on multiple occasions, the dosage varied between 15mg/kg IV 3 times daily and 10mg/kg once daily orally.<span class="elsevierStyleSup">10</span> Treatment duration also varied from 3 to 5 days in the first case and 1 to several weeks in the other one.<span class="elsevierStyleBold"> </span>While results from this study are preliminary, they suggest that in the most severe cases of uncontrolled haemorrhage it would be reasonable to administer anti-fibrinolytic treatment with tranexamic acid. Our patients received doses ranging from 15mg/kg 3 times daily IV to 10mg/kg 3 times daily orally with treatment lasting between 2 and 5 days. All courses of treatment were equally effective. No side effects were observed at any time. However, we recommend administering oral or IV tranexamic acid at the lowest possible effective dosage and during the shortest possible period in order to lessen the risk of adverse effects. In our patients, this dose was 10mg/kg 3 times daily orally during 3 to 4 days. It is possible that treatment lasting less than 3 days could be just as effective, but this type of dose was not studied. Lastly, early at-home use of tranexamic acid by patients with ADPKD and recurrent haematuria could be very cost-effective if it prevented the need for hospitalisation. The main limitations of this study are a small sample size and the lack of an untreated control group.</p><p class="elsevierStylePara">In summary, tranexamic acid may be used safely in selected ADPKD patients with severe or intractable haematuria that does not respond to conventional treatment. The drug can be administered orally or intravenously, and the dose must be adjusted in patients with kidney failure. Treatment with tranexamic acid in ADPKD may preserve renal function both directly, by stopping cyst bleeding and decreasing the frequency of haematuria episodes, and indirectly, by preventing embolisation and/or nephrectomy.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgements</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">This study was partially funded by a grant awarded to R.P. by Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation (EC08/00236) and the research activity intensification programme (<span class="elsevierStyleItalic">Programa Intensificación Actividad Investigadora</span>) at IdiPAZ and Lain-Entralgo/CM.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The authors affirm that they have no conflicts of interest related to the content of this article.</p><p class="elsevierStylePara"><a href="grande/11210_16025_27914_en_t1_11210i.jpg" class="elsevierStyleCrossRefs"><img src="11210_16025_27914_en_t1_11210i.jpg" alt="Clinical data from ADPKD patients before and after medical therapy with tranexamic acid"></img></a></p><p class="elsevierStylePara">Table 1. Clinical data from ADPKD patients before and after medical therapy with tranexamic acid</p><p class="elsevierStylePara"><a href="grande/11210_16025_27916_en_f1_11210i2.jpg" class="elsevierStyleCrossRefs"><img src="11210_16025_27916_en_f1_11210i2.jpg" alt="Magnetic resonance of Case 6 showing numerous renal cysts with signs of intracystic bleeding and fluid-fluid levels"></img></a></p><p class="elsevierStylePara">Figure 1. Magnetic resonance of Case 6 showing numerous renal cysts with signs of intracystic bleeding and fluid-fluid levels</p>" "pdfFichero" => "P1-E534-S3437-A11210-EN.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:6 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec438635" "palabras" => array:1 [ 0 => "PQRAD" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec438637" "palabras" => array:1 [ 0 => "Hemorragia quística" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec438639" "palabras" => array:1 [ 0 => "Hematuria" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec438641" "palabras" => array:1 [ 0 => "Función renal" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec438643" "palabras" => array:1 [ 0 => "Antifibrinolítico" ] ] 5 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec438645" "palabras" => array:1 [ 0 => "Ácido tranexámico" ] ] ] "en" => array:6 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec438636" "palabras" => array:1 [ 0 => "PKD" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec438638" "palabras" => array:1 [ 0 => "Cyst bleeding" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec438640" "palabras" => array:1 [ 0 => "Haematuria" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec438642" "palabras" => array:1 [ 0 => "Renal function" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec438644" "palabras" => array:1 [ 0 => "Anti-fibrinolytic" ] ] 5 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec438646" "palabras" => array:1 [ 0 => "Tranexamic acid" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes</span><span class="elsevierStyleBold">:</span> En la poliquistosis renal autosómica dominante (PQRAD), la hematuria macroscópica por la rotura de quistes renales es una manifestación habitual, que<span class="elsevierStyleSup"> </span>puede ser espontánea o el resultado de un traumatismo, cálculos renales, un tumor o una infección. El sangrado del quiste puede verse prolongado por la activación local de la fibrinólisis por uroquinasa. El manejo de la hematuria, en la mayoría de los pacientes con PQRAD, suele ser conservador con reposo, transfusiones, corrección de las coagulopatías, uso de desmopresina y agentes estimulantes de la eritropoyesis. En algunos casos de hematuria incoercible, puede ser necesaria la embolización y hasta la nefrectomía. Otras modalidades terapéuticas han tratado de evitar la hospitalización prolongada y la nefrectomía, intentando preservar la función renal con la administración de agentes antifibrinolíticos. <span class="elsevierStyleBold">Objetivo</span><span class="elsevierStyleBold">:</span> El objetivo del estudio fue analizar, de forma prospectiva, la respuesta a la administración de ácido tranexámico en pacientes con PQRAD y con hematuria masiva incoercible o que no cede con tratamiento convencional. <span class="elsevierStyleBold">Resultados</span><span class="elsevierStyleBold">:</span> Se evaluó su acción sobre la función renal, así como el desarrollo de efectos secundarios. Un total de ocho pacientes recibieron ácido tranexámico por vía oral o i.v., durante de 2 a 5 días, y en todos los casos la hematuria cedió de forma inmediata o en el plazo de pocos días, manteniendo estables los niveles de hemoglobina y de función renal. No se observaron complicaciones tromboembólicas o de otro tipo. En esta serie de casos, que hasta ahora es el mayor estudio prospectivo que se ha comunicado y el único que incluye diferentes grados de función renal, el ácido tranexámico se confirma como una herramienta prometedora para tratar la hematuria debida a hemorragia quística en la PQRAD. <span class="elsevierStyleBold">Conclusiones</span><span class="elsevierStyleBold">:</span> El ácido tranexámico puede utilizarse de forma segura para el tratamiento de la hematuria sin respuesta a la terapia convencional en la PQRAD. El tratamiento resultó eficaz, tanto en los pacientes con función renal conservada como en aquéllos con insuficiencia renal crónica. El fármaco puede administrarse por vía oral o i.v., siendo necesario ajustar las dosis según el grado de función renal. La terapia con ácido tranexámico puede preservar la función renal directamente, al parar y espaciar los episodios acumulativos de hematuria, o indirectamente, evitando la embolización y la nefrectomía. Es necesario realizar estudios prospectivos controlados y aleatorizados para obtener conclusiones más definitivas.</p>" ] "en" => array:1 [ "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background:</span> Gross haematuria is a common manifestation of autosomal dominant polycystic kidney disease (ADPKD). It can be spontaneous or the result of trauma, renal calculi, tumour, or infection. Spontaneous cyst bleeding is important in this particular group of patients, since it can be prolonged by local activation of fibrinolysis by urokinase. The management of haematuria in ADPKD is usually conservative, including bed rest, blood transfusion, correction of blood disorders, and use of vasopressin and erythropoiesis-stimulating agents. In some patients, the management of gross or life-threatening haematuria may require embolisation and/or nephrectomy. Nonetheless, other methods have been tried to avoid prolonged hospitalisation and nephrectomy and preserve kidney function, such as the use of anti-fibrinolytics. Tranexamic acid was recently suggested as a tool to treat gross haematuria in ADPKD in isolated cases. <span class="elsevierStyleBold">Objective:</span> The aim of this study was to evaluate prospectively the response to tranexamic acid in a group of 8 patients with ADPKD and gross haematuria unresponsive to conventional treatment. <span class="elsevierStyleBold">Results:</span> The massive bleeding stopped within 2 to 5 days in all patients. The haemoglobin level and renal function subsequently stabilised. There were no side effects or thromboembolic events. In this case series, the largest prospective study so far published and the only one including different degrees of renal function, tranexamic acid is confirmed as a promising tool for treating haematuria due to intracystic bleeding in ADPKD. <span class="elsevierStyleBold">Conclusions:</span> In summary, tranexamic acid can be used safely in ADPKD patients with chronic renal impairment or preserved renal function to treat severe haematuria poorly responsive to conventional therapy. Tranexamic acid can be administered orally or IV; and dose adjustment for renal impairment is important. Tranexamic acid therapy may preserve renal function in ADPKD directly, by stopping haematuria episodes, or indirectly, by preventing embolisation and/or nephrectomy. The major limitation of this study is the small sample size and the lack of an untreated control group. We suggest a prospective, randomised controlled study to confirm the efficacy of this treatment, its long-term safety, and the optimal dosage. Further larger and multicentre studies are needed to evaluate the cost-benefit ratio and the limits of this therapy in the clinical setting.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11210_16025_27914_en_t1_11210i.jpg" "Alto" => 1146 "Ancho" => 2225 "Tamanyo" => 1192021 ] ] "descripcion" => array:1 [ "en" => "Clinical data from ADPKD patients before and after medical therapy with tranexamic acid" ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11210_16025_27916_en_f1_11210i2.jpg" "Alto" => 1222 "Ancho" => 1011 "Tamanyo" => 1286873 ] ] "descripcion" => array:1 [ "en" => "Magnetic resonance of Case 6 showing numerous renal cysts with signs of intracystic bleeding and fluid-fluid levels" ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003200000002/v0_201502091616/X2013251412000965/v0_201502091616/en/main.assets" "Apartado" => array:4 [ "identificador" => "35441" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Originals" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003200000002/v0_201502091616/X2013251412000965/v0_201502091616/en/P1-E534-S3437-A11210-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000965?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 12 | 23 |
| 2024 October | 92 | 114 | 206 |
| 2024 September | 75 | 88 | 163 |
| 2024 August | 82 | 99 | 181 |
| 2024 July | 79 | 82 | 161 |
| 2024 June | 105 | 95 | 200 |
| 2024 May | 108 | 75 | 183 |
| 2024 April | 77 | 69 | 146 |
| 2024 March | 83 | 69 | 152 |
| 2024 February | 63 | 56 | 119 |
| 2024 January | 75 | 54 | 129 |
| 2023 December | 56 | 58 | 114 |
| 2023 November | 72 | 85 | 157 |
| 2023 October | 96 | 75 | 171 |
| 2023 September | 86 | 84 | 170 |
| 2023 August | 89 | 58 | 147 |
| 2023 July | 73 | 72 | 145 |
| 2023 June | 55 | 39 | 94 |
| 2023 May | 66 | 56 | 122 |
| 2023 April | 60 | 46 | 106 |
| 2023 March | 40 | 41 | 81 |
| 2023 February | 59 | 41 | 100 |
| 2023 January | 67 | 33 | 100 |
| 2022 December | 69 | 62 | 131 |
| 2022 November | 56 | 51 | 107 |
| 2022 October | 66 | 49 | 115 |
| 2022 September | 62 | 50 | 112 |
| 2022 August | 64 | 72 | 136 |
| 2022 July | 58 | 45 | 103 |
| 2022 June | 57 | 35 | 92 |
| 2022 May | 68 | 53 | 121 |
| 2022 April | 77 | 54 | 131 |
| 2022 March | 94 | 59 | 153 |
| 2022 February | 95 | 51 | 146 |
| 2022 January | 88 | 50 | 138 |
| 2021 December | 58 | 44 | 102 |
| 2021 November | 64 | 64 | 128 |
| 2021 October | 85 | 54 | 139 |
| 2021 September | 70 | 73 | 143 |
| 2021 August | 63 | 56 | 119 |
| 2021 July | 65 | 50 | 115 |
| 2021 June | 63 | 32 | 95 |
| 2021 May | 67 | 43 | 110 |
| 2021 April | 101 | 43 | 144 |
| 2021 March | 94 | 61 | 155 |
| 2021 February | 87 | 37 | 124 |
| 2021 January | 55 | 18 | 73 |
| 2020 December | 47 | 30 | 77 |
| 2020 November | 51 | 18 | 69 |
| 2020 October | 45 | 18 | 63 |
| 2020 September | 48 | 11 | 59 |
| 2020 August | 42 | 13 | 55 |
| 2020 July | 51 | 29 | 80 |
| 2020 June | 41 | 20 | 61 |
| 2020 May | 41 | 13 | 54 |
| 2020 April | 47 | 25 | 72 |
| 2020 March | 52 | 18 | 70 |
| 2020 February | 50 | 18 | 68 |
| 2020 January | 52 | 45 | 97 |
| 2019 December | 63 | 47 | 110 |
| 2019 November | 59 | 33 | 92 |
| 2019 October | 47 | 24 | 71 |
| 2019 September | 63 | 36 | 99 |
| 2019 August | 41 | 25 | 66 |
| 2019 July | 65 | 32 | 97 |
| 2019 June | 44 | 22 | 66 |
| 2019 May | 60 | 50 | 110 |
| 2019 April | 114 | 60 | 174 |
| 2019 March | 48 | 33 | 81 |
| 2019 February | 24 | 24 | 48 |
| 2019 January | 54 | 20 | 74 |
| 2018 December | 122 | 41 | 163 |
| 2018 November | 151 | 26 | 177 |
| 2018 October | 170 | 37 | 207 |
| 2018 September | 84 | 15 | 99 |
| 2018 August | 60 | 24 | 84 |
| 2018 July | 61 | 21 | 82 |
| 2018 June | 52 | 20 | 72 |
| 2018 May | 62 | 15 | 77 |
| 2018 April | 74 | 6 | 80 |
| 2018 March | 59 | 23 | 82 |
| 2018 February | 65 | 10 | 75 |
| 2018 January | 66 | 11 | 77 |
| 2017 December | 90 | 20 | 110 |
| 2017 November | 70 | 8 | 78 |
| 2017 October | 65 | 13 | 78 |
| 2017 September | 63 | 17 | 80 |
| 2017 August | 40 | 17 | 57 |
| 2017 July | 55 | 19 | 74 |
| 2017 June | 70 | 9 | 79 |
| 2017 May | 65 | 27 | 92 |
| 2017 April | 53 | 20 | 73 |
| 2017 March | 33 | 15 | 48 |
| 2017 February | 94 | 49 | 143 |
| 2017 January | 59 | 28 | 87 |
| 2016 December | 80 | 9 | 89 |
| 2016 November | 93 | 15 | 108 |
| 2016 October | 140 | 16 | 156 |
| 2016 September | 207 | 8 | 215 |
| 2016 August | 237 | 9 | 246 |
| 2016 July | 228 | 18 | 246 |
| 2016 June | 153 | 0 | 153 |
| 2016 May | 174 | 0 | 174 |
| 2016 April | 135 | 0 | 135 |
| 2016 March | 109 | 0 | 109 |
| 2016 February | 134 | 0 | 134 |
| 2016 January | 141 | 0 | 141 |
| 2015 December | 150 | 0 | 150 |
| 2015 November | 132 | 0 | 132 |
| 2015 October | 105 | 0 | 105 |
| 2015 September | 96 | 0 | 96 |
| 2015 August | 94 | 0 | 94 |
| 2015 July | 113 | 0 | 113 |
| 2015 June | 57 | 0 | 57 |
| 2015 May | 85 | 0 | 85 |
| 2015 April | 6 | 0 | 6 |
Show all
