Letter to the Editor
Combined liver and kidney transplantation in two women with primary hyperoxaluria: Different roads led to different outcomes
Trasplante combinado de hígado y riñón en dos pacientes con hiperoxaluria primaria – quando diferentes caminos conducen a diferentes resultados
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"Rita" "apellidos" => "Leal" "email" => array:1 [ 0 => "rita.gcleal@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Joana" "apellidos" => "Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Telma" "apellidos" => "Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ana" "apellidos" => "Galvão" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Lidia" "apellidos" => "Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Catarina" "apellidos" => "Romãzinho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Fernando" "apellidos" => "Macário" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Rui" "apellidos" => "Alves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Mario" "apellidos" => "Campos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "Emanuel" "apellidos" => "Furtado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 10 => array:3 [ "nombre" => "Alfredo" "apellidos" => "Mota" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Serviço de Nefrologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidade de Transplantação Hepática, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Serviço de Urologia e Transplantação Renal, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trasplante combinado de hígado y riñón en dos pacientes con hiperoxaluria primaria – quando diferentes caminos conducen a diferentes resultados" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report on two patients with end-stage renal disease (ESRD) due to primary hyperoxaluria type 1 (PH1) who underwent liver-kidney transplant (LKT), using different approaches and consequently with different outcomes.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first patient is a 32-year-old woman with ESRD on intensive daily hemodialysis (HD) due to PH-1 (homozygous mutation g.12261G>T) with severe systemic oxalosis. Three years after the beginning of dialysis, she underwent a combined simultaneous LKT from a deceased 48-year-old donor. The postoperative period was uneventful and she had immediate diuresis and excellent hepatic function. In an attempt to decrease the serum oxalate pool, continuous venovenous hemodiafiltration was performed for the first 72<span class="elsevierStyleHsp" style=""></span>h, followed by intensive HD. Her plasma oxalate levels (pOx) progressively decreased while her urinary oxalate levels (uOx) increased at the same rate (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Three months post-transplant her serum creatinine (sCr) was 1.6<span class="elsevierStyleHsp" style=""></span>mg/dL pre HD and a renal graft biopsy was performed revealing oxalate deposits on the tubules and intersticium. Intermittent HD was continued for six months and after stopping dialysis she was kept under immunosuppression, bicarbonate therapy and high fluid intake. Although her pOx reached low levels (17<span class="elsevierStyleHsp" style=""></span>μmol/L, normal range<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3–11<span class="elsevierStyleHsp" style=""></span>μmol/dL), one year after LKT, graft dysfunction was present with sCr 4.5<span class="elsevierStyleHsp" style=""></span>mg/dL. Nevertheless, skin oxalosis, refractory anemia and ventricular dysfunction secondary to oxalate deposits had completely disappeared.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second case is a 26-year-old female with ESRD due to genetic confirmed PH-1 (homozygous mutation p.I244T) non-responsive to pyridoxine on regular HD, also with systemic oxalosis, however to a lesser degree.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In this case sequential LKT was proposed and she underwent a liver transplant from a deceased donor, three years after the beginning of HD. She was kept on intermittent HD four times a week and her pOx levels were measured sequentially in order to evaluate the best timing for sequential kidney transplant (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Four months after the liver transplant, pOx was 18<span class="elsevierStyleHsp" style=""></span>μmol/L, so she was proposed for kidney transplant and received a renal graft from a 54 years old deceased donor. The post-operative period was uneventful and she was discharged with sCr of 1.5<span class="elsevierStyleHsp" style=""></span>mg/dL, without performing any dialysis session. One year post-transplant, she has stable sCr of 1.3<span class="elsevierStyleHsp" style=""></span>mg/dL, pOx levels of 15<span class="elsevierStyleHsp" style=""></span>μmol/L, uOx levels of 13<span class="elsevierStyleHsp" style=""></span>μmol/L with no signs of recurrent oxalosis.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">PH-1 is a rare metabolic disorder characterized by a dysfunction of the liver-specific enzyme alanine-glyoxalate aminotransferase resulting in excessive oxalate production. The deposition of calcium oxalate (CaOx) in the kidney leads to chronic kidney disease (CKD) and subsequent plasma CaOx saturation (plasma oxalate >30<span class="elsevierStyleHsp" style=""></span>μmol/L) with systemic oxalosis.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnosis of PH-1 is often delayed and about 30% of the patients first present with CKD.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Once ESRD is present, intensive dialysis might no be able to remove CaOx efficiently and the risk of systemic oxalosis increases worsening the prognosis. Thus, some authors recommend planning pre-emptive transplantation at CKD stage 3-b.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Since isolated kidney transplantation is frequently followed by recurrence of nephrocalcinosis due to the unremitting overproduction of oxalate, combined LK transplant has been accepted as the optimal approach to patients with PH-1 and ESRD.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Combined LKT strategies are challenging, especially if systemic oxalosis is present. Sequential combined transplant (liver transplantation first) offers a metabolic advantage, since there is a correction of the enzyme defect, stopping oxalate production and allowing effective oxalate removal by HD before kidney transplant.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> Simultaneous liver kidney transplantation has an immunologic advantage because the liver graft apparently has the potential to protect a simultaneously transplanted kidney from rejection, limits surgery risks and is more feasible regarding organ shortage.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The first patient described presented severe systemic oxalosis with expected rebound of oxalate levels, which was why HD was continued for six months after transplant. Despite the progressively decreasing pOx levels, there was a concomitant increase of uOx levels that overcame the graft filtration capacity resulting in precocious recurrent oxalosis.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding the second patient, a sequential LKT was preferred followed by serial measurements of pOx to set the right timing for kidney transplantation. There is no consensus of the optimal pOx levels for which the risk of recurrence is lower but since ESRD patients without PH-1 have higher oxalate levels than the normal range, when our patient presented pOx of 18<span class="elsevierStyleHsp" style=""></span>μmol/dL, we felt confident to proceed to kidney transplantation with great results.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, sequential transplant seems to be a better option in patients with PH-1 and ESRD with high oxalate load. The timing for kidney transplant after liver is not well defined but pOx sequential quantification and support therapy with intensive dialysis appears to be good approaches. Simultaneous transplant can be an option if the patient has low oxalate burden and less dialysis time. Either way, timely diagnosis with prevention of ESRD and pre-emptive liver transplant might be the best option.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interest regarding the publication of this manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Discussion" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:2 [ "identificador" => "xack291661" "titulo" => "Acknowledgements" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">C-HDF: continuous haemodiafiltration; Tx: transplant; HD: haemodialysis; d: day; h: hour; M: month.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pre Tx \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">72<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">10<span class="elsevierStyleHsp" style=""></span>d \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">1<span class="elsevierStyleHsp" style=""></span>M \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3<span class="elsevierStyleHsp" style=""></span>M \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6<span class="elsevierStyleHsp" style=""></span>M \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">1A \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">sCr (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">uOx (mg/24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">255 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pOx (μmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dialysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HD pre surg. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C-HDF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="3" align="left" valign="top">Intermittent HD 4/week</td><td class="td" title="table-entry " align="left" valign="top">Stop HD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1476025.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of 24-h urinary and plasma oxalate (uOx; pOx), serum creatinine (sCr) and dialysis treatment for patient 1.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Tx: transplant; LK Tx: liver kidney transplant; HD: haemodialysis; d: day; h: hour; M: month.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pre Tx \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3<span class="elsevierStyleHsp" style=""></span>M Pos liver Tx \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6<span class="elsevierStyleHsp" style=""></span>M Pos LK Tx \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">sCr (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">uOx (mg/24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pOx (μmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dialysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1476024.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evolution of 24-h urinary and plasma oxalate (uOx; pOx), serum creatinine (sCr) and dialysis treatment for patient 2.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hiperoxaluria primaria" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V. 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| 2021 Febrero | 72 | 37 | 109 |
| 2021 Enero | 58 | 30 | 88 |
| 2020 Diciembre | 38 | 19 | 57 |
| 2020 Noviembre | 39 | 21 | 60 |
| 2020 Octubre | 27 | 24 | 51 |
| 2020 Septiembre | 51 | 31 | 82 |
| 2020 Agosto | 48 | 32 | 80 |
| 2020 Julio | 37 | 16 | 53 |
| 2020 Junio | 39 | 22 | 61 |
| 2020 Mayo | 36 | 25 | 61 |
| 2020 Abril | 24 | 15 | 39 |
| 2020 Marzo | 30 | 24 | 54 |
| 2020 Febrero | 37 | 21 | 58 |
| 2020 Enero | 40 | 22 | 62 |
| 2019 Diciembre | 56 | 38 | 94 |
| 2019 Noviembre | 29 | 14 | 43 |
| 2019 Octubre | 32 | 23 | 55 |
| 2019 Septiembre | 50 | 27 | 77 |
| 2019 Agosto | 33 | 14 | 47 |
| 2019 Julio | 31 | 25 | 56 |
| 2019 Junio | 23 | 25 | 48 |
| 2019 Mayo | 33 | 20 | 53 |
| 2019 Abril | 60 | 23 | 83 |
| 2019 Marzo | 44 | 29 | 73 |
| 2019 Febrero | 29 | 18 | 47 |
| 2019 Enero | 28 | 20 | 48 |
| 2018 Diciembre | 168 | 58 | 226 |
| 2018 Noviembre | 305 | 29 | 334 |
| 2018 Octubre | 266 | 31 | 297 |
| 2018 Septiembre | 139 | 18 | 157 |
| 2018 Agosto | 94 | 27 | 121 |
| 2018 Julio | 62 | 22 | 84 |
| 2018 Junio | 77 | 25 | 102 |
| 2018 Mayo | 68 | 18 | 86 |
| 2018 Abril | 143 | 15 | 158 |
| 2018 Marzo | 115 | 16 | 131 |
| 2018 Febrero | 109 | 14 | 123 |
| 2018 Enero | 60 | 14 | 74 |
| 2017 Diciembre | 99 | 17 | 116 |
| 2017 Noviembre | 61 | 15 | 76 |
| 2017 Octubre | 68 | 15 | 83 |
| 2017 Septiembre | 190 | 22 | 212 |
| 2017 Agosto | 133 | 13 | 146 |
| 2017 Julio | 87 | 13 | 100 |
| 2017 Junio | 91 | 14 | 105 |
| 2017 Mayo | 72 | 9 | 81 |
| 2017 Abril | 83 | 19 | 102 |
| 2017 Marzo | 62 | 8 | 70 |
| 2017 Febrero | 39 | 6 | 45 |
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