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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report on two patients with end-stage renal disease &#40;ESRD&#41; due to primary hyperoxaluria type 1 &#40;PH1&#41; who underwent liver-kidney transplant &#40;LKT&#41;&#44; using different approaches and consequently with different outcomes&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first patient is a 32-year-old woman with ESRD on intensive daily hemodialysis &#40;HD&#41; due to PH-1 &#40;homozygous mutation g&#46;12261G&#62;T&#41; with severe systemic oxalosis&#46; Three years after the beginning of dialysis&#44; she underwent a combined simultaneous LKT from a deceased 48-year-old donor&#46; The postoperative period was uneventful and she had immediate diuresis and excellent hepatic function&#46; In an attempt to decrease the serum oxalate pool&#44; continuous venovenous hemodiafiltration was performed for the first 72<span class="elsevierStyleHsp" style=""></span>h&#44; followed by intensive HD&#46; Her plasma oxalate levels &#40;pOx&#41; progressively decreased while her urinary oxalate levels &#40;uOx&#41; increased at the same rate &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Three months post-transplant her serum creatinine &#40;sCr&#41; was 1&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL pre HD and a renal graft biopsy was performed revealing oxalate deposits on the tubules and intersticium&#46; Intermittent HD was continued for six months and after stopping dialysis she was kept under immunosuppression&#44; bicarbonate therapy and high fluid intake&#46; Although her pOx reached low levels &#40;17<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#44; normal range<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#8211;11<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;dL&#41;&#44; one year after LKT&#44; graft dysfunction was present with sCr 4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Nevertheless&#44; skin oxalosis&#44; refractory anemia and ventricular dysfunction secondary to oxalate deposits had completely disappeared&#46;</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 &#40;homozygous mutation p&#46;I244T&#41; non-responsive to pyridoxine on regular HD&#44; also with systemic oxalosis&#44; however to a lesser degree&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In this case sequential LKT was proposed and she underwent a liver transplant from a deceased donor&#44; three years after the beginning of HD&#46; 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 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Four months after the liver transplant&#44; pOx was 18<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#44; so she was proposed for kidney transplant and received a renal graft from a 54 years old deceased donor&#46; The post-operative period was uneventful and she was discharged with sCr of 1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; without performing any dialysis session&#46; One year post-transplant&#44; she has stable sCr of 1&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; pOx levels of 15<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#44; uOx levels of 13<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L with no signs of recurrent oxalosis&#46;</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&#46; The deposition of calcium oxalate &#40;CaOx&#41; in the kidney leads to chronic kidney disease &#40;CKD&#41; and subsequent plasma CaOx saturation &#40;plasma oxalate &#62;30<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#41; with systemic oxalosis&#46;<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&#37; of the patients first present with CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Once ESRD is present&#44; intensive dialysis might no be able to remove CaOx efficiently and the risk of systemic oxalosis increases worsening the prognosis&#46; Thus&#44; some authors recommend planning pre-emptive transplantation at CKD stage 3-b&#46;<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&#44; combined LK transplant has been accepted as the optimal approach to patients with PH-1 and ESRD&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Combined LKT strategies are challenging&#44; especially if systemic oxalosis is present&#46; Sequential combined transplant &#40;liver transplantation first&#41; offers a metabolic advantage&#44; since there is a correction of the enzyme defect&#44; stopping oxalate production and allowing effective oxalate removal by HD before kidney transplant&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;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&#44; limits surgery risks and is more feasible regarding organ shortage&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The first patient described presented severe systemic oxalosis with expected rebound of oxalate levels&#44; which was why HD was continued for six months after transplant&#46; Despite the progressively decreasing pOx levels&#44; there was a concomitant increase of uOx levels that overcame the graft filtration capacity resulting in precocious recurrent oxalosis&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding the second patient&#44; a sequential LKT was preferred followed by serial measurements of pOx to set the right timing for kidney transplantation&#46; 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&#44; when our patient presented pOx of 18<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;dL&#44; we felt confident to proceed to kidney transplantation with great results&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; sequential transplant seems to be a better option in patients with PH-1 and ESRD with high oxalate load&#46; 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&#46; Simultaneous transplant can be an option if the patient has low oxalate burden and less dialysis time&#46; Either way&#44; timely diagnosis with prevention of ESRD and pre-emptive liver transplant might be the best option&#46;</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&#46;</p></span></span>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">C-HDF&#58; continuous haemodiafiltration&#59; Tx&#58; transplant&#59; HD&#58; haemodialysis&#59; d&#58; day&#59; h&#58; hour&#59; M&#58; month&#46;</p>"
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                  \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&nbsp;\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&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">255&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
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    "bibliografia" => array:2 [
      "titulo" => "References"
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          "identificador" => "bibs0005"
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              "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&#46; Lorenzo-Sellares"
                            1 => "A&#46; Torres-Ramirez"
                            2 => "E&#46; Salido"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3265/Nefrologia.pre2014.Jan.12335"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nefrologia"
                        "fecha" => "2014"
                        "volumen" => "34"
                        "paginaInicial" => "398"
                        "paginaFinal" => "412"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24798559"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Delayed diagnosis of primary hyperoxaluria in a young patient with advanced chronic renal failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Gonzales"
                            1 => "B&#46; G&#243;mes Giralda"
                            2 => "C&#46; Ruiz-Zorrilla Lop&#233;z"
                            3 => "M&#46; Acosta Ochoa"
                            4 => "K&#46; Ampuero Anachuri"
                            5 => "A&#46; Mollina Miguel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3265/Nefrologia.pre2010.Nov.10725"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nefrologia"
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                        "volumen" => "31"
                        "paginaInicial" => "227"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21461022"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary hyperoxaluria type 1&#58; indications for screening and guidance for diagnosis and tratment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Cochat"
                            1 => "S&#46; Hulton"
                            2 => "C&#46; Acquaviva"
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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
Rita Leala,
Corresponding author
rita.gcleal@gmail.com

Corresponding author.
, Joana Costaa, Telma Santosa, Ana Galvãoa, Lidia Santosa, Catarina Romãzinhoa, Fernando Macárioa, Rui Alvesa, Mario Camposa, Emanuel Furtadob, Alfredo Motac
a Serviço de Nefrologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
b Unidade de Transplantação Hepática, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
c Serviço de Urologia e Transplantação Renal, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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    "titulo" => "Combined liver and kidney transplantation in two women with primary hyperoxaluria&#58; Different roads led to different outcomes"
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        "titulo" => "Trasplante combinado de h&#237;gado y ri&#241;&#243;n en dos pacientes con hiperoxaluria primaria &#8211; quando diferentes caminos conducen a diferentes resultados"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report on two patients with end-stage renal disease &#40;ESRD&#41; due to primary hyperoxaluria type 1 &#40;PH1&#41; who underwent liver-kidney transplant &#40;LKT&#41;&#44; using different approaches and consequently with different outcomes&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first patient is a 32-year-old woman with ESRD on intensive daily hemodialysis &#40;HD&#41; due to PH-1 &#40;homozygous mutation g&#46;12261G&#62;T&#41; with severe systemic oxalosis&#46; Three years after the beginning of dialysis&#44; she underwent a combined simultaneous LKT from a deceased 48-year-old donor&#46; The postoperative period was uneventful and she had immediate diuresis and excellent hepatic function&#46; In an attempt to decrease the serum oxalate pool&#44; continuous venovenous hemodiafiltration was performed for the first 72<span class="elsevierStyleHsp" style=""></span>h&#44; followed by intensive HD&#46; Her plasma oxalate levels &#40;pOx&#41; progressively decreased while her urinary oxalate levels &#40;uOx&#41; increased at the same rate &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Three months post-transplant her serum creatinine &#40;sCr&#41; was 1&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL pre HD and a renal graft biopsy was performed revealing oxalate deposits on the tubules and intersticium&#46; Intermittent HD was continued for six months and after stopping dialysis she was kept under immunosuppression&#44; bicarbonate therapy and high fluid intake&#46; Although her pOx reached low levels &#40;17<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#44; normal range<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#8211;11<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;dL&#41;&#44; one year after LKT&#44; graft dysfunction was present with sCr 4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Nevertheless&#44; skin oxalosis&#44; refractory anemia and ventricular dysfunction secondary to oxalate deposits had completely disappeared&#46;</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 &#40;homozygous mutation p&#46;I244T&#41; non-responsive to pyridoxine on regular HD&#44; also with systemic oxalosis&#44; however to a lesser degree&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In this case sequential LKT was proposed and she underwent a liver transplant from a deceased donor&#44; three years after the beginning of HD&#46; 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 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Four months after the liver transplant&#44; pOx was 18<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#44; so she was proposed for kidney transplant and received a renal graft from a 54 years old deceased donor&#46; The post-operative period was uneventful and she was discharged with sCr of 1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; without performing any dialysis session&#46; One year post-transplant&#44; she has stable sCr of 1&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; pOx levels of 15<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#44; uOx levels of 13<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L with no signs of recurrent oxalosis&#46;</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&#46; The deposition of calcium oxalate &#40;CaOx&#41; in the kidney leads to chronic kidney disease &#40;CKD&#41; and subsequent plasma CaOx saturation &#40;plasma oxalate &#62;30<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#41; with systemic oxalosis&#46;<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&#37; of the patients first present with CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Once ESRD is present&#44; intensive dialysis might no be able to remove CaOx efficiently and the risk of systemic oxalosis increases worsening the prognosis&#46; Thus&#44; some authors recommend planning pre-emptive transplantation at CKD stage 3-b&#46;<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&#44; combined LK transplant has been accepted as the optimal approach to patients with PH-1 and ESRD&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Combined LKT strategies are challenging&#44; especially if systemic oxalosis is present&#46; Sequential combined transplant &#40;liver transplantation first&#41; offers a metabolic advantage&#44; since there is a correction of the enzyme defect&#44; stopping oxalate production and allowing effective oxalate removal by HD before kidney transplant&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;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&#44; limits surgery risks and is more feasible regarding organ shortage&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The first patient described presented severe systemic oxalosis with expected rebound of oxalate levels&#44; which was why HD was continued for six months after transplant&#46; Despite the progressively decreasing pOx levels&#44; there was a concomitant increase of uOx levels that overcame the graft filtration capacity resulting in precocious recurrent oxalosis&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding the second patient&#44; a sequential LKT was preferred followed by serial measurements of pOx to set the right timing for kidney transplantation&#46; 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&#44; when our patient presented pOx of 18<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;dL&#44; we felt confident to proceed to kidney transplantation with great results&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; sequential transplant seems to be a better option in patients with PH-1 and ESRD with high oxalate load&#46; 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&#46; Simultaneous transplant can be an option if the patient has low oxalate burden and less dialysis time&#46; Either way&#44; timely diagnosis with prevention of ESRD and pre-emptive liver transplant might be the best option&#46;</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&#46;</p></span></span>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">111&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 20132514
Original language: English
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