De novo tacrolimus ' associated hemolytic uremic syndrome after renal transplantation - Case report
De novo tacrolimus ¿ associated hemolytic uremic syndrome after renal transplantation - Case report
Leído
11150
Vecesse ha leído el artículo
2685
Total PDF
8465
Total HTML
Compartir estadísticas
array:20 [ "pii" => "X0211699513002410" "issn" => "02116995" "doi" => "10.3265/Nefrologia.pre2012.Oct.11793" "estado" => "S300" "fechaPublicacion" => "2013-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2013;33:152-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6281 "formatos" => array:3 [ "EPUB" => 346 "HTML" => 5212 "PDF" => 723 ] ] "Traduccion" => array:1 [ "en" => array:17 [ "pii" => "X2013251413002418" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2012.Oct.11793" "estado" => "S300" "fechaPublicacion" => "2013-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2013;33:152-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4338 "formatos" => array:3 [ "EPUB" => 311 "HTML" => 3535 "PDF" => 492 ] ] "en" => array:7 [ "idiomaDefecto" => true "titulo" => "De novo tacrolimus ' associated hemolytic uremic syndrome after renal transplantation - Case report" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "152" "paginaFinal" => "154" ] ] "contieneTextoCompleto" => 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" => "11793_16025_37614_en_t111793.jpg" "Alto" => 945 "Ancho" => 1419 "Tamanyo" => 283053 ] ] "descripcion" => array:1 [ "en" => "Laboratorial evolution" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Patrícia Neto, Karina Lopes, Fernando Macário, Rui Alves, Alfredo Mota, Mário Campos" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Patrícia" "apellidos" => "Neto" ] 1 => array:2 [ "nombre" => "Karina" "apellidos" => "Lopes" ] 2 => array:2 [ "nombre" => "Fernando" "apellidos" => "Macário" ] 3 => array:2 [ "nombre" => "Rui" "apellidos" => "Alves" ] 4 => array:2 [ "nombre" => "Alfredo" "apellidos" => "Mota" ] 5 => array:2 [ "nombre" => "Mário" "apellidos" => "Campos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X0211699513002410" "doi" => "10.3265/Nefrologia.pre2012.Oct.11793" "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/X0211699513002410?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251413002418?idApp=UINPBA000064" "url" => "/20132514/0000003300000001/v0_201502091555/X2013251413002418/v0_201502091556/en/main.assets" ] ] "itemAnterior" => array:17 [ "pii" => "X0211699513002429" "issn" => "02116995" "doi" => "10.3265/Nefrologia.pre2012.Nov.11677" "estado" => "S300" "fechaPublicacion" => "2013-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2013;33:150-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6551 "formatos" => array:3 [ "EPUB" => 317 "HTML" => 5580 "PDF" => 654 ] ] "es" => array:11 [ "idiomaDefecto" => true "titulo" => "Necrosis cutánea recidivante de origen multifactorial en paciente en hemodiálisis" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "150" "paginaFinal" => "152" ] ] "contieneResumen" => array:1 [ "es" => 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" => "11677_108_38150_es_11677_f1.jpg" "Alto" => 323 "Ancho" => 600 "Tamanyo" => 180438 ] ] "descripcion" => array:1 [ "es" => "Imágenes macro y microscópicas de las lesiones" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Adoración Martín-Gómez, M. Eugenia Palacios, José Roig-Álvaro, José L. Martínez-Amo Gámez, Sergio A. García-Marcos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Adoración" "apellidos" => "Martín-Gómez" ] 1 => array:2 [ "nombre" => "M. Eugenia" "apellidos" => "Palacios" ] 2 => array:2 [ "nombre" => "José" "apellidos" => "Roig-Álvaro" ] 3 => array:2 [ "nombre" => "José L." "apellidos" => "Martínez-Amo Gámez" ] 4 => array:2 [ "nombre" => "Sergio A." "apellidos" => "García-Marcos" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X2013251413002426" "doi" => "10.3265/Nefrologia.pre2012.Nov.11677" "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/X2013251413002426?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699513002429?idApp=UINPBA000064" "url" => "/02116995/0000003300000001/v0_201502091331/X0211699513002429/v0_201502091334/es/main.assets" ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "De novo tacrolimus ' associated hemolytic uremic syndrome after renal transplantation - Case report " "subtitulo" => "Hemolytic Uremic Syndrome after Transplantation" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "152" "paginaFinal" => "154" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Patrícia Neto, Karina Lopes, Fernando Macário, Rui Alves, Alfredo Mota, Mário Campos" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Patrícia" "apellidos" => "Neto" "email" => array:1 [ 0 => "patriciaaires3@sapo.pt" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "Karina" "apellidos" => "Lopes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "nombre" => "Fernando" "apellidos" => "Macário" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Rui" "apellidos" => "Alves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "nombre" => "Alfredo" "apellidos" => "Mota" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 5 => array:3 [ "nombre" => "Mário" "apellidos" => "Campos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Serviço de Nefrologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Serviço de Urologia e Transplantação Renal, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "De novo tacrolimus ¿ associated hemolytic uremic syndrome after renal transplantation - Case report" ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor,</span></p><p class="elsevierStylePara">De novo Hemolytic Uremic Syndrome (HUS) occurs in 1-5% of renal transplant recipients, most frequently within the first 3 months after transplantation.<span class="elsevierStyleSup">1,2</span></p><p class="elsevierStylePara">Thrombotic Microangiopathy (TMA) usually sets in the first weeks post-transplant when patients are treated with high dose of immunosuppressant.</p><p class="elsevierStylePara">De novo TMA has been documented in approximately 1% of patients receiving tacrolimus.<span class="elsevierStyleSup">2</span> Calcineurin inhibitor – induced nephrotoxicity primarily results from dose dependent renal arteriolar vasoconstriction,<span class="elsevierStyleSup">3</span> owing of the enhanced production of vasoconstrictive factors, particularly endothelin-1 and angiotensin II.<span class="elsevierStyleSup">4,5 </span>Moreover, calcineurin inhibitors might promote a procoagulant state enhancing platelet aggregation and activating plasminogen activator.<span class="elsevierStyleSup">6 </span>De novo post-transplant HUS has been reported both with the use of an mTOR inhibitor alone and in combination therapy.<span class="elsevierStyleSup">7</span> The viral infections, to which patients on immunosuppression are susceptible, have been implicated in pathogenesis of de novo HUS in organ transplant recipients. A CMV infection<span class="elsevierStyleSup">8</span> has been associated with both the novo and recurrent<span class="elsevierStyleSup">9 </span>forms of post-transplant HUS. Parvovirus B19 and polioma BK virus infection have also been associated with de novo HUS in renal transplant recipients.<span class="elsevierStyleSup">10-12</span></p><p class="elsevierStylePara">The authors describe the clinical case of a Caucasian male, 33 years old with a history of chronic kidney disease of unknown etiology, in hemodialysis for nearly 7 years, with past medical history of severe hypertension, severe hypertriglyceridemia and chronic pancreatitis. Family history was irrelevant.</p><p class="elsevierStylePara">In May 2010 he was underwent a renal transplantation with deceased kidney allograft (donor: man aged 23, suffered TCE) with CMV (D + / R +), HBV, HCV and HIV negative and with ABO compatibility. In the presence of low immunological risk situation with PRA 0% and with HLA 4:6 matches, he did not submitted to induction and began a immunosuppression regimen with mycophenolic acid (1440 mg/day), Tacrolimus LP (0.15mg/kg), methylprednisolone (8mg/kg) and adopting an initial maintenance scheme comprising mycophenolic acid (1440mg/day), LP tacrolimus (16mg) and prednisone (20mg/day).</p><p class="elsevierStylePara">Initial graft function was immediate, without surgical complications but with severe hypertension of difficult to control. Doppler renal graft was performed that excluded vascular complications and showed a normal resistance index.</p><p class="elsevierStylePara">The 2nd day postoperatively for 3rd day there was a deterioration of renal graft function (serum creatinine of 2.92 to 3.15mg/dL) associated with abrupt drop in platelet count (97,000 to 19.000/μL), drop in serum hemoglobin (10.4 to 7.6g/dL) and increase serum levels of lactate dehydrogenase (LDH 1485U/L) with tacrolimus plasma level of 10ng/mL. The Coombs test (direct and indirect) was negative, serum haptoglobin decreased and were found 3% of schistocytes in peripheral blood smear.</p><p class="elsevierStylePara">The survey of CMV, BK virus and parvovirus B19 in blood by P.C.R. were negative. It was found normal plasma activity of the ADAMTS13 in the absence of inhibitors. The autoimmunity study with anti-nuclear antibodies, anti-dsDNA and anti-cytoplasmic antibodies and antiphospholipid antibody were negative as well as was negative donor-specific antibody. In relation to severity of thrombocytopenia was not possible to perform biopsy of renal allograft.</p><p class="elsevierStylePara">The patient remained clinically well and without gastrointestinal or neurological changes. Given the evidence of worsening of renal function (acute dysfunction of renal allograft) associated with markers of intravascular hemolysis (nonimmune: Coombs direct and indirect negative) was established the diagnosis of <span class="elsevierStyleItalic">De novo</span> hemolytic uremic syndrome post-transplant, probably associated with tacrolimus.</p><p class="elsevierStylePara">We suspended tacrolimus and mycophenolic acid (by myelosuppressive effects) and was introduced everolimus on the 5<span class="elsevierStyleSup">th</span> day. We obtained improved of blood pressure control. Despite the attitudes adopted on the 9<span class="elsevierStyleSup">th</span> day maintained parameters hemolysis (6.6g Hb/dL, and 31,000/μL platelet LDH 926U/L) and worsening of graft function (7.24mg/dL) with diuresis maintained (Table 1). We decided to initiate daily plasmapheresis (D9 to D23) (1.5 x the plasma volume) with fresh frozen plasma inactivated. The patient remained without neurological disorders. After 14 sessions of plasmapheresis and 3 daily hemodialysis sessions (D9 to D12) we observed recovery of renal graft function accompanied by the disappearance of markers of hemolysis. At discharge date he had a serum creatinine of 2.39 mg/dL and 6 months after the level of seric creatinine was of 1.0mg/dL, with no evidence of recurrent HUS (without analytical signal of intravascular hemolysis).</p><p class="elsevierStylePara">There are no treatment guidelines for this entity. Among 29 patients with De novo post-transplant TMA, 80% recovered graft function after cyclosporine stop and plasma therapy.<span class="elsevierStyleSup">13</span> Our experience demonstrates that switching from tacrolimus to everolimus with plasmapheresis with fresh plasma proved be an adequate strategy for this situation without increased risk of acute rejection.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interest</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The authors declare that there is no conflict of interest associated with this manuscript.</p><p class="elsevierStylePara"><a href="grande/11793_16025_37614_en_t111793.jpg" class="elsevierStyleCrossRefs"><img src="11793_16025_37614_en_t111793.jpg" alt="Laboratorial evolution"></img></a></p><p class="elsevierStylePara">Table 1. Laboratorial evolution</p>" "pdfFichero" => "P1-E547-S3873-A11793.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Pham PT, Peng A, Wilkinson AH, Gritsch HA, Lassman C, Pham PC, et al. Cyclosporine and tacrolimus associated thrombotic microangiopathy. Am J Kidney Dis 2000;(36):844-50." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Reynolds JC, Agodoa LY, Yuan CM, Abbott KC. Thrombotic microangiopathy after renal transplantation in the United States. Am J Kidney Dis 2003;(42):1058-68." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "English J, Evan A, Houghton DC, Bennett WM. Cyclosporine-induced acute renal dysfunction in the rat. Evidence of arteriolar vasoconstriction with preservation of tubular function. Transplantation 1987;(44):135-41." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Naesens M, Kuypers DR, Sarwal M. Calcineurin ¿inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;(4):481-508." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Lanese DM, Conger JD. Effects on endothelin receptor antagonists on cyclosporine-induced vasoconstriction in isolated rat renal arterioles. J Clin Invest 1993;(91):2144-9." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Ponticelli C. De novo trombotic microangiopathy: an underrated complication of renal transplantations. Clin Nephrol 2007;(67):335-40." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Robson M, Côte I, Abbs I, Koffman G, Goldsmith D, et al. Trombotic microangiopathy with sirolimus ¿based immunossupression: potentiation of calcineurin inhibitor-induced endothelial damage? Am J Transplant 2003;(3):324-7." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Waiser J, Budde K, Rudolph B, Ortner MA, Neumayer HH, et al. De novo hemolytic uremic syndrome postrenal transplant after cytomegalovirus infection. Am J Kidney Dis 1999;(34):556-9." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:1 [ "itemHostRev" => array:3 [ "pii" => "S0873215912000323" "estado" => "S300" "issn" => "08732159" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Olie KH, Goodship TH, Verlaak R, Florquin S, Groothoff JW, Strain L, et al. Post transplantation cytomegalovirus-induced recurrence on atypical hemolytic uremic syndrome associate with a factor H mutation: successful treatment with intensive plasma exchanges and ganciclovir. Am J Kidney Dis 2005;45(1):e12-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15696434" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Ardalan MR, Shoja MM, Tubbs RS, Esmaili H, Keyvani H. Postrenal transplant hematophagocytic lymphohistiocytosis and thrombotic microangiopathy associated with parvovirus B19 infection. Am J Transplant 2008;8:1340-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18522549" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Murer L, Zacchello G, Bianchi D, Dall'Amico R, Montini G, Andreetta B, et al. Thrombotic microangiophaty associated with parvovirus b19 infection after renal transplantation. J Am Soc Nephrol 2000;11:1132-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10820178" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Petrogiannis-Haliotis T, Sakoulas G, Kirby J, Koralnik IJ, Dvorak AM, Monahan-Earley R, et al. BK-related polyomavirus vasculopathy in a renal ¿transplant recipient. N Engl J Med 2001;345:1250-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11680445" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Karthikeyan V, Parasuraman R, Shah V, Vera E, Venkat KK. Outcome of plasma exchange therapy in thrombotic microangiopathy after renal transplantation. Am J Transplant 2003;(3):1289-94." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02116995/0000003300000001/v0_201502091331/X0211699513002410/v0_201502091334/en/main.assets" "Apartado" => array:4 [ "identificador" => "35346" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas al Director - Casos clínicos breves" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02116995/0000003300000001/v0_201502091331/X0211699513002410/v0_201502091334/en/P1-E547-S3873-A11793.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699513002410?idApp=UINPBA000064" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 10 | 13 | 23 |
| 2024 Octubre | 60 | 44 | 104 |
| 2024 Septiembre | 91 | 24 | 115 |
| 2024 Agosto | 81 | 59 | 140 |
| 2024 Julio | 58 | 35 | 93 |
| 2024 Junio | 65 | 37 | 102 |
| 2024 Mayo | 98 | 47 | 145 |
| 2024 Abril | 54 | 33 | 87 |
| 2024 Marzo | 42 | 43 | 85 |
| 2024 Febrero | 33 | 25 | 58 |
| 2024 Enero | 39 | 21 | 60 |
| 2023 Diciembre | 25 | 24 | 49 |
| 2023 Noviembre | 36 | 29 | 65 |
| 2023 Octubre | 39 | 29 | 68 |
| 2023 Septiembre | 40 | 27 | 67 |
| 2023 Agosto | 48 | 26 | 74 |
| 2023 Julio | 47 | 17 | 64 |
| 2023 Junio | 43 | 22 | 65 |
| 2023 Mayo | 67 | 29 | 96 |
| 2023 Abril | 32 | 30 | 62 |
| 2023 Marzo | 59 | 34 | 93 |
| 2023 Febrero | 38 | 26 | 64 |
| 2023 Enero | 42 | 24 | 66 |
| 2022 Diciembre | 54 | 36 | 90 |
| 2022 Noviembre | 49 | 37 | 86 |
| 2022 Octubre | 56 | 49 | 105 |
| 2022 Septiembre | 51 | 40 | 91 |
| 2022 Agosto | 46 | 47 | 93 |
| 2022 Julio | 60 | 51 | 111 |
| 2022 Junio | 101 | 43 | 144 |
| 2022 Mayo | 65 | 46 | 111 |
| 2022 Abril | 55 | 53 | 108 |
| 2022 Marzo | 57 | 46 | 103 |
| 2022 Febrero | 49 | 46 | 95 |
| 2022 Enero | 60 | 45 | 105 |
| 2021 Diciembre | 56 | 47 | 103 |
| 2021 Noviembre | 56 | 46 | 102 |
| 2021 Octubre | 61 | 62 | 123 |
| 2021 Septiembre | 61 | 40 | 101 |
| 2021 Agosto | 59 | 29 | 88 |
| 2021 Julio | 80 | 40 | 120 |
| 2021 Junio | 68 | 27 | 95 |
| 2021 Mayo | 60 | 32 | 92 |
| 2021 Abril | 154 | 99 | 253 |
| 2021 Marzo | 107 | 40 | 147 |
| 2021 Febrero | 82 | 36 | 118 |
| 2021 Enero | 59 | 33 | 92 |
| 2020 Diciembre | 63 | 17 | 80 |
| 2020 Noviembre | 39 | 14 | 53 |
| 2020 Octubre | 32 | 22 | 54 |
| 2020 Septiembre | 45 | 20 | 65 |
| 2020 Agosto | 70 | 28 | 98 |
| 2020 Julio | 44 | 14 | 58 |
| 2020 Junio | 48 | 17 | 65 |
| 2020 Mayo | 60 | 16 | 76 |
| 2020 Abril | 31 | 20 | 51 |
| 2020 Marzo | 44 | 19 | 63 |
| 2020 Febrero | 62 | 17 | 79 |
| 2020 Enero | 61 | 27 | 88 |
| 2019 Diciembre | 55 | 31 | 86 |
| 2019 Noviembre | 47 | 18 | 65 |
| 2019 Octubre | 32 | 15 | 47 |
| 2019 Septiembre | 30 | 24 | 54 |
| 2019 Agosto | 26 | 20 | 46 |
| 2019 Julio | 40 | 25 | 65 |
| 2019 Junio | 38 | 24 | 62 |
| 2019 Mayo | 34 | 24 | 58 |
| 2019 Abril | 96 | 39 | 135 |
| 2019 Marzo | 57 | 27 | 84 |
| 2019 Febrero | 40 | 24 | 64 |
| 2019 Enero | 47 | 24 | 71 |
| 2018 Diciembre | 108 | 47 | 155 |
| 2018 Noviembre | 173 | 26 | 199 |
| 2018 Octubre | 131 | 23 | 154 |
| 2018 Septiembre | 108 | 14 | 122 |
| 2018 Agosto | 79 | 16 | 95 |
| 2018 Julio | 74 | 21 | 95 |
| 2018 Junio | 101 | 20 | 121 |
| 2018 Mayo | 81 | 18 | 99 |
| 2018 Abril | 91 | 19 | 110 |
| 2018 Marzo | 92 | 13 | 105 |
| 2018 Febrero | 65 | 11 | 76 |
| 2018 Enero | 60 | 9 | 69 |
| 2017 Diciembre | 88 | 9 | 97 |
| 2017 Noviembre | 73 | 8 | 81 |
| 2017 Octubre | 63 | 9 | 72 |
| 2017 Septiembre | 64 | 10 | 74 |
| 2017 Agosto | 69 | 10 | 79 |
| 2017 Julio | 88 | 10 | 98 |
| 2017 Junio | 80 | 15 | 95 |
| 2017 Mayo | 70 | 11 | 81 |
| 2017 Abril | 75 | 8 | 83 |
| 2017 Marzo | 50 | 5 | 55 |
| 2017 Febrero | 57 | 9 | 66 |
| 2017 Enero | 29 | 5 | 34 |
| 2016 Diciembre | 67 | 6 | 73 |
| 2016 Noviembre | 94 | 11 | 105 |
| 2016 Octubre | 118 | 16 | 134 |
| 2016 Septiembre | 183 | 1 | 184 |
| 2016 Agosto | 226 | 4 | 230 |
| 2016 Julio | 246 | 7 | 253 |
| 2016 Junio | 153 | 0 | 153 |
| 2016 Mayo | 135 | 0 | 135 |
| 2016 Abril | 135 | 0 | 135 |
| 2016 Marzo | 123 | 0 | 123 |
| 2016 Febrero | 126 | 0 | 126 |
| 2016 Enero | 117 | 0 | 117 |
| 2015 Diciembre | 148 | 0 | 148 |
| 2015 Noviembre | 103 | 0 | 103 |
| 2015 Octubre | 103 | 0 | 103 |
| 2015 Septiembre | 84 | 0 | 84 |
| 2015 Agosto | 96 | 0 | 96 |
| 2015 Julio | 111 | 0 | 111 |
| 2015 Junio | 71 | 0 | 71 |
| 2015 Mayo | 124 | 0 | 124 |
| 2015 Abril | 27 | 0 | 27 |
| 2015 Marzo | 12 | 0 | 12 |
Mostrar todo
