Letter to the Editor
Late onset of de novo atypical hemolytic–uremic syndrome presented on a simultaneous pancreas and kidney transplant recipient successfully treated with eculizumab
Presentacion tardía de síndrome hemolítico–urémico atípico de novo en receptor de trasplante reno-pancreático resuelto con eculizumab
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"etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Neus" "apellidos" => "Sala" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Dolores" "apellidos" => "López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Laura" "apellidos" => "Cañas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Josep" "apellidos" => "Bonet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Ricardo" "apellidos" => "Lauzurica" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía patológica, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Presentacion tardía de síndrome hemolítico–urémico atípico de novo en receptor de trasplante reno-pancreático resuelto con eculizumab" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 742 "Ancho" => 986 "Tamanyo" => 268695 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Acute TMA showing thrombosis at glomerular capillaries and mesangiolysis (Masson's trichrome stain).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atypical hemolytic–uremic syndrome (aHUS) is an extremely rare, genetic, chronic, and progressive inflammatory disease<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> caused by defects in complement system. These defects result in systemic thrombotic microangiopathy involving damage to multiple organ systems including renal dysfunction.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–7</span></a> Genetic mutations have been detected in around 50% of the reported cases. Regarding renal transplant patients, expanded criteria donors, infection by cytomegalovirus or BK, use of CNI or m-TOR inhibitors and antibody-mediated rejection (AMR) have been related to de novo post-transplant aHUS.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Graft failure is reported in 60–90% of patients within 1 year.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Eculizumab is a monoclonal antibody that binds to C5 complement protein avoiding the formation of the cell membrane attack complex.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> We report herein a case of late onset of de novo post-transplant aHUS on a simultaneous pancreas and kidney recipient with severe systemic manifestations, without presenting acute graft rejection, successfully treated with limited doses of eculizumab remaining stable after one year of follow-up.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 46-year-old woman with end stage renal disease secondary to type 1 Diabetes Mellitus underwent simultaneous pancreas and kidney transplant on October 2012 from deceased donor. Received induction with Basiliximab and maintenance treatment with mycophenolate mofetil, tacrolimus, and prednisone. Pancreatic and renal function were stable, creatinine (SCr) of 110<span class="elsevierStyleHsp" style=""></span>μmol/L. Tacrolimus through levels remained between 6 and 8<span class="elsevierStyleHsp" style=""></span>ng/ml. Seven months after transplant presented fever, abdominal pain, diarrhea and vomiting, acute graft dysfunction (SCr 438<span class="elsevierStyleHsp" style=""></span>μmol/L) and thrombocytopenia (53<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>9/L). She developed progressive anemia and thrombocytopenia and worsening of renal function requiring dialysis. Pancreas graft function remained preserved. Thrombotyc microangiopathy (TMA)was detected with lactate dehydrogenase (LDH) up to 1500<span class="elsevierStyleHsp" style=""></span>UI/L, undetectable haptoglobin and schistocytes. C3 was low, ADAMTS 13 of 79% and Shigella toxin was negative. Urinary tract infection by extended-spectrum beta-lactamase (ESBL)-klebsiella was present. Initial biopsy confirmed findings of TMA with severe tubulo-interstitial involvement and some focal glomerular involvement, without features of acute rejection. Discontinuation of tacrolimus, antibiotic treatment with meropenem and daily plasma exchange (PE) for 10 days were performed. The patient did not respond to therapy. Second renal biopsy showed persistent signs of TMA, worsening involvement of glomeruli with mesangiolysis without rejection (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Treatment with Eculizumab was started with 4 doses of 900<span class="elsevierStyleHsp" style=""></span>mg Eculizumab iv on a weekly basis, showing improvement of renal function, cessation of hemodialysis and hemolysis. Genetic screening did not detect mutations on factor I, factor H or factor MCP genes. Risk haplotype in heterozygosis for factor H and MCP genes were observed. Study of the complement alternate pathway showed low factor C3, factor H, normal expression of MCP (membrane cofactor protein) and negative anti-factor H antibodies. A third biopsy was performed showing predominance of chronic lessions of TMA and mild signs of acute TMA with interstitial fibrosis of 5–10% and some microhemorrhages, with ATN (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). New course of 3 daily PE and final dose of 1200<span class="elsevierStyleHsp" style=""></span>mg of Eculizumab iv were prescribed. She presented normalized C3, LDH, haptoglobin, hemoglobin and platelets. At discharge Scr was 300<span class="elsevierStyleHsp" style=""></span>μmol/L. Immunosupresive maintenance therapy at discharge was prednisone and mycophenolate mofetil. Renal function continued to improve and at 3 months Scr was 180<span class="elsevierStyleHsp" style=""></span>μmol/L, with no signs of hemolysis and the patient remained asymptomatic over one year of follow-up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In contrast to previous reports<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> in our case the appearance of aHUS was late, at seven moths post-transplant, was not related with rejection nor with high plasmatic levels of tacrolimus. The patient did not show identified mutations and did not respond to correction of potential triggers. The pancreatic graft function remained always normal. After administration of limited doses of eculizumab, the renal function required three months to achieve SCr levels of 180<span class="elsevierStyleHsp" style=""></span>μmol/L and then remained stable, without hemolytic activity or symptoms. This highlights the importance of an early diagnosis and promptly treatment with eculizumab in order to improve renal and systemic results. In our case limited doses of eculizumab provided sustained improvement. Further evidence is needed to establish the optimal dosing in different clinical settings.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 742 "Ancho" => 986 "Tamanyo" => 268695 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Acute TMA showing thrombosis at glomerular capillaries and mesangiolysis (Masson's trichrome stain).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 744 "Ancho" => 990 "Tamanyo" => 278737 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Interstitial fibrosis of 5–10% and some microhemorrhages. 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Pesavento" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-6143.2010.03178.x" "Revista" => array:5 [ "tituloSerie" => "Am J Transplant" "fecha" => "2010" "volumen" => "10" "paginaInicial" => "1804" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20659088" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Le Quintrec" 1 => "J. Zuber" 2 => "B. Moulin" 3 => "N. Kamar" 4 => "M. Jablonski" 5 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 2 | 5 |
| 2024 October | 41 | 40 | 81 |
| 2024 September | 39 | 28 | 67 |
| 2024 August | 47 | 62 | 109 |
| 2024 July | 27 | 31 | 58 |
| 2024 June | 46 | 35 | 81 |
| 2024 May | 44 | 31 | 75 |
| 2024 April | 35 | 27 | 62 |
| 2024 March | 34 | 19 | 53 |
| 2024 February | 34 | 34 | 68 |
| 2024 January | 23 | 19 | 42 |
| 2023 December | 18 | 29 | 47 |
| 2023 November | 25 | 42 | 67 |
| 2023 October | 59 | 23 | 82 |
| 2023 September | 28 | 22 | 50 |
| 2023 August | 35 | 28 | 63 |
| 2023 July | 26 | 19 | 45 |
| 2023 June | 42 | 18 | 60 |
| 2023 May | 44 | 36 | 80 |
| 2023 April | 26 | 16 | 42 |
| 2023 March | 41 | 16 | 57 |
| 2023 February | 36 | 19 | 55 |
| 2023 January | 27 | 18 | 45 |
| 2022 December | 37 | 30 | 67 |
| 2022 November | 44 | 31 | 75 |
| 2022 October | 40 | 38 | 78 |
| 2022 September | 45 | 37 | 82 |
| 2022 August | 40 | 56 | 96 |
| 2022 July | 35 | 43 | 78 |
| 2022 June | 50 | 35 | 85 |
| 2022 May | 43 | 31 | 74 |
| 2022 April | 79 | 37 | 116 |
| 2022 March | 71 | 48 | 119 |
| 2022 February | 36 | 42 | 78 |
| 2022 January | 29 | 35 | 64 |
| 2021 December | 37 | 45 | 82 |
| 2021 November | 44 | 33 | 77 |
| 2021 October | 44 | 37 | 81 |
| 2021 September | 36 | 29 | 65 |
| 2021 August | 40 | 36 | 76 |
| 2021 July | 44 | 44 | 88 |
| 2021 June | 48 | 22 | 70 |
| 2021 May | 63 | 44 | 107 |
| 2021 April | 133 | 94 | 227 |
| 2021 March | 39 | 46 | 85 |
| 2021 February | 43 | 24 | 67 |
| 2021 January | 49 | 17 | 66 |
| 2020 December | 39 | 20 | 59 |
| 2020 November | 33 | 20 | 53 |
| 2020 October | 23 | 20 | 43 |
| 2020 September | 33 | 21 | 54 |
| 2020 August | 35 | 27 | 62 |
| 2020 July | 39 | 24 | 63 |
| 2020 June | 33 | 35 | 68 |
| 2020 May | 36 | 11 | 47 |
| 2020 April | 26 | 21 | 47 |
| 2020 March | 25 | 15 | 40 |
| 2020 February | 40 | 30 | 70 |
| 2020 January | 51 | 40 | 91 |
| 2019 December | 33 | 24 | 57 |
| 2019 November | 38 | 25 | 63 |
| 2019 October | 34 | 12 | 46 |
| 2019 September | 22 | 16 | 38 |
| 2019 August | 13 | 18 | 31 |
| 2019 July | 13 | 22 | 35 |
| 2019 June | 22 | 22 | 44 |
| 2019 May | 25 | 28 | 53 |
| 2019 April | 58 | 59 | 117 |
| 2019 March | 32 | 18 | 50 |
| 2019 February | 19 | 19 | 38 |
| 2019 January | 33 | 25 | 58 |
| 2018 December | 118 | 39 | 157 |
| 2018 November | 163 | 20 | 183 |
| 2018 October | 125 | 22 | 147 |
| 2018 September | 56 | 20 | 76 |
| 2018 August | 41 | 12 | 53 |
| 2018 July | 32 | 12 | 44 |
| 2018 June | 49 | 15 | 64 |
| 2018 May | 38 | 13 | 51 |
| 2018 April | 77 | 11 | 88 |
| 2018 March | 41 | 9 | 50 |
| 2018 February | 35 | 6 | 41 |
| 2018 January | 48 | 7 | 55 |
| 2017 December | 40 | 8 | 48 |
| 2017 November | 41 | 12 | 53 |
| 2017 October | 30 | 7 | 37 |
| 2017 September | 35 | 13 | 48 |
| 2017 August | 28 | 30 | 58 |
| 2017 July | 21 | 25 | 46 |
| 2017 June | 33 | 14 | 47 |
| 2017 May | 31 | 15 | 46 |
| 2017 April | 29 | 14 | 43 |
| 2017 March | 9 | 4 | 13 |
| 2017 February | 16 | 12 | 28 |
| 2017 January | 15 | 10 | 25 |
| 2016 December | 22 | 9 | 31 |
| 2016 November | 45 | 14 | 59 |
| 2016 October | 52 | 9 | 61 |
| 2016 September | 84 | 9 | 93 |
| 2016 August | 5 | 0 | 5 |
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