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Perrando, Resistencia, Chaco, Argentina, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Unidad de Ablación e Implante Renal, Hospital Dr. Julio C. Perrando, Resistencia, Chaco, Argentina, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "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" => "12657_16025_64452_en_t1_12657.jpg" "Alto" => 643 "Ancho" => 1419 "Tamanyo" => 287287 ] ] "descripcion" => array:1 [ "en" => "Number of cases of miss match, viruria, viraemia, renal function and biopsy in patients with active infection due to BK virus" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor,</span></p><p class="elsevierStylePara">BK virus (BKV) has a high prevalence in the world population (> 80%). Although it does not cause disease in immunocompetent patients, it remains latent in the kidneys and urinary tract<span class="elsevierStyleSup">1</span>.</p><p class="elsevierStylePara">Its reactivation in renal transplant recipients can lead to BKV-associated nephropathy (BKVAN). There is no specific treatment and the therapeutic strategy consists on the change of immunosuppressive drugs or dose adjustment. The correct detection and monitoring of this virus is crucial, since early intervention could prevent said disease<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara">Active viral infection may be confused or coexist with cellular rejection, but they are two opposing entities, so it is essential to differentiate them.</p><p class="elsevierStylePara">Renal biopsy is the gold standard for BKVAN diagnosis<span class="elsevierStyleSup">2,3</span>. However, real time PCR (polymerase chain reaction) makes it possible to quantify viral load and detect patients at risk for nephropathy before tissue damage occurs<span class="elsevierStyleSup">4,5</span>.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Objective: </span>To analyse the incidence of active BKV infection and the development of BKVAN in patients during their first two years after renal transplantation.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">We studied 70 kidney recipients in the Renal Transplant Unit of Dr. Julio C. Perrando Hospital; 62 of them received kidneys from cadaveric donors. Urine samples were included for BKV screening in patients who were in their first two years post-transplantation (viruria was monitored every three months during the first two years; if levels of viruria >10<span class="elsevierStyleSup">7</span> copies/mL, plasma detection was performed).</p><p class="elsevierStylePara">Patients received induction with daclizumab/baxilzumab-methylprednisolone-mycophenolate-mofetil (MMF) and maintenance with tacrolimus-MMF-steroids.</p><p class="elsevierStylePara">DNAs were extracted using commercial columns (Quick-gDNA MiniPrep, Zymo Research, U.S.A.).</p><p class="elsevierStylePara">Qualitative real-time PCR was performed, using primers according to Randhawa et al<span class="elsevierStyleSup">5</span>. Positive samples were quantified by commercial Q-PCR Alert (Nanogen Advanced Diagnostics SRL®).</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Viruria was detected >10<span class="elsevierStyleSup">7</span> copies/mL in 12 of the 70 patients (17%), but only 5 had persistent viruria, the others were transient.</p><p class="elsevierStylePara">Active infection was between 3 and 24 months after transplantation, with positive viraemia after 12 months.</p><p class="elsevierStylePara">Half the patients with viruria also suffered from renal function deterioration (creatinine > 1.4mg/dL).</p><p class="elsevierStylePara">Table 1 shows the number of cases of mismatch, renal function, biopsy, viruria and viraemia in patients with persistent levels of viruria.</p><p class="elsevierStylePara">BKVAN was confirmed by biopsy in 1 patient, and therefore had an incidence of 1.4% in our centre.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case report</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara">55 year-old patient who received a cadaveric transplant. Induction: daclizumab-tacrolimus-MMF-steroids. Maintenance: tacrolimus-MMF-steroids. Creatinine 1mg/dL and 1.2mg/dL; creatinine clearance: 96mL, no proteinuria. Nine months after transplantation, the patient presented viruria (10<span class="elsevierStyleSup">7</span> copies/mL) for BKV without renal dysfunction and with negative viraemia. High levels of viruria persisted with negative viraemia, which became positive at month 12 (> 10<span class="elsevierStyleSup">4 </span>copies/mL); biopsy findings: interstitial nephritis, tubular nuclear alterations related to BKV. The patient was switched to sirolimus 2mg/day and ciprofloxacin 500mg/day (10 days) is added. The patient maintained stable renal function values, clearance 86mL, without proteinuria and decreased viral load in blood and urine. Currently, the patient has still his kidney and does not require dialysis.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The prevalence of BKV in the urine of renal transplant patients ranges from 18%-40%: Shenagari et al.<span class="elsevierStyleSup">6</span> report 40%, Costa et al. 18,3%<span class="elsevierStyleSup">7</span> and Viscount et al. 24%<span class="elsevierStyleSup">4</span>. Reactivation usually occurs within the first two months post-transplant<span class="elsevierStyleSup">8</span>. In our study, we determined viral load in plasma in the 5 patients with persistent viruria, 2 had viral loads> 10<span class="elsevierStyleSup">4</span> copies/mL, similar to other reports, in one patient BKVAN was found by biopsy, and the other patient had a non-conclusive biopsy. BKVAN lesions are multifocal with random distribution, and can give false negatives<span class="elsevierStyleSup">3</span>.</p><p class="elsevierStylePara">Hirsch et al.<span class="elsevierStyleSup">9</span> monitored BKV replication during the first year after transplant, and found the highest values of viruria and viraemia (25.4% and 13.7%, respectively) 6 months after transplantation.</p><p class="elsevierStylePara">Babel et al.<span class="elsevierStyleSup">10</span> showed that 21.4% of patients with persistent viruria developed BKVAN between 5 and 11 weeks after reactivation in urine and blood. In our patient with BKVAN, viruria appeared 12 weeks before viraemia and this became positive almost simultaneously with biopsy findings, without clinical signs of renal dysfunction (no protocol biopsies performed in the centre).</p><p class="elsevierStylePara">In addition to immunosuppression, other factors such as inflammation and host immunity should be considered in the pathogenesis of BKVAN.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The positivity of PCR in urine may be the first finding indicative of BKV reactivation. In our patient, screening determined a significant and persistent viral load in urine 12 weeks before viraemia, which could be an advantage for early detection of reactivation and allow adjustment of immunosuppression, although viraemia is more strongly associated with the development nephropathy. The data reported are useful, since so far no literature has been published on the incidence of BKV reactivation in renal transplantation in Argentina.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article.</p><p class="elsevierStylePara"><a href="grande/12657_16025_64452_en_t1_12657.jpg" class="elsevierStyleCrossRefs"><img src="12657_16025_64452_en_t1_12657.jpg" alt="Number of cases of miss match, viruria, viraemia, renal function and biopsy in patients with active infection due to BK virus "></img></a></p><p class="elsevierStylePara">Table 1. Number of cases of miss match, viruria, viraemia, renal function and biopsy in patients with active infection due to BK virus </p>" "pdfFichero" => "P1-E577-S4809-A12657-EN.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12657_16025_64452_en_t1_12657.jpg" "Alto" => 643 "Ancho" => 1419 "Tamanyo" => 287287 ] ] "descripcion" => array:1 [ "en" => "Number of cases of miss match, viruria, viraemia, renal function and biopsy in patients with active infection due to BK virus" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Polo C, Pérez JL, Mielnichuck A, Fedele CG, Niubo J, Tenorio A. 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Year/Month | Html | Total | |
---|---|---|---|
2024 November | 7 | 3 | 10 |
2024 October | 56 | 44 | 100 |
2024 September | 71 | 39 | 110 |
2024 August | 82 | 76 | 158 |
2024 July | 49 | 32 | 81 |
2024 June | 78 | 29 | 107 |
2024 May | 78 | 34 | 112 |
2024 April | 53 | 29 | 82 |
2024 March | 45 | 24 | 69 |
2024 February | 44 | 33 | 77 |
2024 January | 39 | 28 | 67 |
2023 December | 38 | 94 | 132 |
2023 November | 37 | 29 | 66 |
2023 October | 71 | 29 | 100 |
2023 September | 84 | 31 | 115 |
2023 August | 54 | 14 | 68 |
2023 July | 73 | 24 | 97 |
2023 June | 45 | 17 | 62 |
2023 May | 68 | 27 | 95 |
2023 April | 58 | 10 | 68 |
2023 March | 81 | 25 | 106 |
2023 February | 46 | 20 | 66 |
2023 January | 73 | 14 | 87 |
2022 December | 57 | 27 | 84 |
2022 November | 73 | 24 | 97 |
2022 October | 54 | 36 | 90 |
2022 September | 78 | 27 | 105 |
2022 August | 61 | 42 | 103 |
2022 July | 47 | 47 | 94 |
2022 June | 41 | 36 | 77 |
2022 May | 36 | 32 | 68 |
2022 April | 55 | 64 | 119 |
2022 March | 105 | 57 | 162 |
2022 February | 42 | 41 | 83 |
2022 January | 64 | 33 | 97 |
2021 December | 75 | 33 | 108 |
2021 November | 48 | 34 | 82 |
2021 October | 48 | 37 | 85 |
2021 September | 51 | 35 | 86 |
2021 August | 66 | 43 | 109 |
2021 July | 52 | 38 | 90 |
2021 June | 48 | 34 | 82 |
2021 May | 47 | 40 | 87 |
2021 April | 135 | 80 | 215 |
2021 March | 89 | 47 | 136 |
2021 February | 104 | 24 | 128 |
2021 January | 55 | 28 | 83 |
2020 December | 45 | 19 | 64 |
2020 November | 46 | 17 | 63 |
2020 October | 38 | 34 | 72 |
2020 September | 32 | 9 | 41 |
2020 August | 58 | 16 | 74 |
2020 July | 48 | 16 | 64 |
2020 June | 60 | 18 | 78 |
2020 May | 67 | 12 | 79 |
2020 April | 71 | 28 | 99 |
2020 March | 50 | 15 | 65 |
2020 February | 62 | 24 | 86 |
2020 January | 84 | 18 | 102 |
2019 December | 101 | 27 | 128 |
2019 November | 92 | 27 | 119 |
2019 October | 79 | 16 | 95 |
2019 September | 81 | 22 | 103 |
2019 August | 100 | 34 | 134 |
2019 July | 69 | 27 | 96 |
2019 June | 79 | 33 | 112 |
2019 May | 97 | 20 | 117 |
2019 April | 124 | 33 | 157 |
2019 March | 61 | 23 | 84 |
2019 February | 37 | 24 | 61 |
2019 January | 46 | 24 | 70 |
2018 December | 88 | 41 | 129 |
2018 November | 88 | 14 | 102 |
2018 October | 100 | 14 | 114 |
2018 September | 78 | 11 | 89 |
2018 August | 62 | 17 | 79 |
2018 July | 50 | 17 | 67 |
2018 June | 58 | 13 | 71 |
2018 May | 63 | 13 | 76 |
2018 April | 72 | 8 | 80 |
2018 March | 73 | 6 | 79 |
2018 February | 61 | 8 | 69 |
2018 January | 62 | 4 | 66 |
2017 December | 71 | 10 | 81 |
2017 November | 63 | 11 | 74 |
2017 October | 55 | 8 | 63 |
2017 September | 52 | 13 | 65 |
2017 August | 58 | 9 | 67 |
2017 July | 36 | 10 | 46 |
2017 June | 45 | 14 | 59 |
2017 May | 50 | 13 | 63 |
2017 April | 45 | 17 | 62 |
2017 March | 33 | 6 | 39 |
2017 February | 41 | 12 | 53 |
2017 January | 18 | 5 | 23 |
2016 December | 54 | 5 | 59 |
2016 November | 89 | 4 | 93 |
2016 October | 137 | 10 | 147 |
2016 September | 186 | 1 | 187 |
2016 August | 210 | 7 | 217 |
2016 July | 176 | 4 | 180 |
2016 June | 132 | 0 | 132 |
2016 May | 155 | 0 | 155 |
2016 April | 111 | 0 | 111 |
2016 March | 105 | 0 | 105 |
2016 February | 114 | 0 | 114 |
2016 January | 116 | 0 | 116 |
2015 December | 104 | 0 | 104 |
2015 November | 90 | 0 | 90 |
2015 October | 114 | 0 | 114 |
2015 September | 74 | 0 | 74 |
2015 August | 89 | 0 | 89 |
2015 July | 97 | 0 | 97 |
2015 June | 51 | 0 | 51 |
2015 May | 54 | 0 | 54 |
2015 April | 17 | 0 | 17 |