Letter to the Editor
Adenovirus infection—A rare cause of interstitial nephritis in kidney transplant
Infección por adenovirus: una causa poco frecuente de nefritis intersticial en el trasplante de riñón
Carla L. Moreiraa,
, Joana Rochab, Margarida Silvac, Joana Silvad, Manuela Almeidaa, Sofia Pedrosoa, Ramon Vizcaínoc, La Salete Martinsa, Leonídio Diasa, António Castro Henriquesa, António Cabritaa
Corresponding author
moreira.l.s.carla@gmail.com
Corresponding author at: Serviço de Nefrologia, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
Corresponding author at: Serviço de Nefrologia, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
a Nephrology Department, Centro Hospitalar Universitário do Porto, Hospital Geral de Santo António, Porto, Portugal
b Nephrology Department, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal
c Pathology Department, Centro Hospitalar Universitário do Porto, Hospital Geral de Santo António, Porto, Portugal
d Nephrology Department, Hospital Garcia da Orta, EPE, Almada, Portugal
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Kidney involvement in transplant recipients more frequently manifests as hemorrhagic cystitis and tubulo-interstitial nephritis.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> The incidence of asymptomatic viremia has been observed in up to 11% within the first year following solid organ transplantation.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present a case of a 40-year-old man who underwent kidney transplantation (KT) of low immunological risk from a living unrelated donor. Induction therapy included basiliximab 20<span class="elsevierStyleHsp" style=""></span>mg (D0 and D4 after surgery), methylprednisolone (250<span class="elsevierStyleHsp" style=""></span>mg, 125<span class="elsevierStyleHsp" style=""></span>mg, 62.5<span class="elsevierStyleHsp" style=""></span>mg on D1, D2 and D3, respectively) followed by prednisolone at a daily dose of 20<span class="elsevierStyleHsp" style=""></span>mg, tacrolimus and mycophenolate de mofetil (1000<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h)—both started a week before KT. On D7 he referred dysuria and urinalysis revealed leucocyturia which prompted ceftriaxone start. He was discharged on D8 after KT, with a serum creatinine (SCr) level of 1.6<span class="elsevierStyleHsp" style=""></span>mg/dL and fluctuating tacrolimus through levels between 5.0 and 10.7<span class="elsevierStyleHsp" style=""></span>ng/mL. Maintenance immunosuppression was achieved with tacrolimus (6.5<span class="elsevierStyleHsp" style=""></span>mg/day), prednisolone (15<span class="elsevierStyleHsp" style=""></span>mg/day) and mycophenolate mofetil (1000<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h). Additional chemoprophylaxis was completed with cothrimoxazol 480<span class="elsevierStyleHsp" style=""></span>mg/daily.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On D17 after KT, the patient presented to the emergency department with fever, diarrhea and renal dysfunction (SCr 2.0<span class="elsevierStyleHsp" style=""></span>mg/dL). Spot urinalysis documented microscopic hematuria and leucocyturia. Graft doppler ultrasonography was normal. He was diagnosed with pyelonephritis and intravenous ceftriaxone was started. His toddler developed superior respiratory infection a couple days before. Despite the start of antibiotic, fever persisted and SCr level increased up to 2.2<span class="elsevierStyleHsp" style=""></span>mg/dL. Initial blood, stool and urine cultures, as well as blood polymerase chain reaction (PCR) for cytomegalovirus (CMV) and polyomavirus, stool PCR for rotavirus, noravirus, astrovirus and clostridium were negative. On D23, the antibiotic was stopped and an allograft biopsy was performed, revealing interstitial nephritis with granulomatous-like appearance and ground glass tubular epithelial cell nuclei suggesting viral inclusions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Immunoperoxidase stain was negative for polyomavirus and immunofluorescence was negative for C4d. The result of serum, urine and kidney tissue PCR was positive for adenovirus. These findings prompted mycophenolate mofetil withhold plus intravenous ganciclovir (2.5<span class="elsevierStyleHsp" style=""></span>mg/kg for 13 days) and intravenous immunoglobulin (IVIG 2<span class="elsevierStyleHsp" style=""></span>mg/kg for 4 days) start. Fever remitted in four days and allograft function improved (SCr 1.9<span class="elsevierStyleHsp" style=""></span>mg/dL on D34 after surgery). Upgrading dosing of mycophenolate mophetil was slowly introduced two weeks after kidney biopsy and valganciclovir (450<span class="elsevierStyleHsp" style=""></span>mg twice daily) was maintained until serum adenovirus PCR became negative after 54 days of treatment. Allograft function slowly improved and SCr stabilized at 1.7<span class="elsevierStyleHsp" style=""></span>mg/dL six months after transplantation.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Native kidneys’ acute interstitial nephritis (AIN) is more commonly associated with drugs. In contrast, drug-induced AIN is rarely reported in kidney grafts, possibly due to the use of corticosteroids in maintenance immunosuppression strategy. Lymphocytic interstitial infiltrates can be observed in any type of acute renal allograft dysfunction, including calcineurin inhibitors nephrotoxicity, acute tubular necrosis and viral infections, as well as in normally functioning renal allografts.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Diagnosis can be challenging as AIN and acute cellular rejection share histological features, namely a primarily composed lymphocyte interstitial infiltrate, with prominent number of eosinophils.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In this case report, patient's therapy included many potential AIN inducers, such as antibiotics, and tacrolimus fluctuating through levels could portend an acute rejection.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Granulomatous AIN can be found with mycobacterial, fungal, and viral infections, such as adenovirus, human immunodeficiency virus, CMV and polyomavirus, which were all negative in our patient, except for adenovirus. Kidney biopsy in adenovirus infection often shows interstitial nephritis with viral inclusions in tubular epithelial cells. Granulomatous interstitial nephritis with neutrophilic inflammation, red blood cells in tubules, and parenchymal necrosis is also more frequent in adenovirus than polyomavirus or CMV infection.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Another supporting feature of adenovirus-induced AIN is the presence of granulomas surrounding tubules.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In this case, the presence of enlarged tubular epithelial cells with groundglass homogenous intranuclear viral inclusions, suggested a viral etiology and the distinctive pattern of granulomatous infiltrate helped discriminate acute rejection from adenovirus infection.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Adenovirus infection in KT recipients should be considered whenever a KT recipient presents with unexplained voiding dysfunction, hematuria, and sterile pyuria. There is uncertainty regarding monitoring of this virus, but early diagnosis with reduction of immunosuppression is essential to virus clearance and allograft function.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Unlike CMV infection, there is no consensual therapeutic approach for AIN associated with adenovirus infection. Treatment strategies are based on case reports and series of cases, which include immunosuppression tapering and specific antiviral therapy, such as IVIG, pulse–dose steroids, cidofovir, ribavirin or valganciclovir, in varying combinations, with or without reduction in immunosuppression.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> Given the inherent toxicity associated to most of these drugs, we report the successful treatment of adenovirus-induced AIN with ganciclovir, IVIG, imunossupression reduction and valganciclovir extended treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1326 "Ancho" => 758 "Tamanyo" => 252863 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Light microscopy shows (A) interstitial nephritis and ill-defined granuloma formation surrounding tubules (hematoxylin and eosin stain; original magnification, 40×) and (B) intranuclear viral inclusion (hematoxylin and eosin stain; original magnification, 60×).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemorrhagic cystitis secondary to adenovirus infection in a kidney transplant recipient: case report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 5 | 15 |
| 2024 October | 69 | 36 | 105 |
| 2024 September | 71 | 33 | 104 |
| 2024 August | 79 | 59 | 138 |
| 2024 July | 52 | 26 | 78 |
| 2024 June | 70 | 38 | 108 |
| 2024 May | 60 | 39 | 99 |
| 2024 April | 56 | 39 | 95 |
| 2024 March | 53 | 29 | 82 |
| 2024 February | 60 | 30 | 90 |
| 2024 January | 44 | 28 | 72 |
| 2023 December | 69 | 30 | 99 |
| 2023 November | 127 | 37 | 164 |
| 2023 October | 58 | 29 | 87 |
| 2023 September | 66 | 35 | 101 |
| 2023 August | 50 | 24 | 74 |
| 2023 July | 63 | 34 | 97 |
| 2023 June | 49 | 16 | 65 |
| 2023 May | 66 | 165 | 231 |
| 2023 April | 75 | 25 | 100 |
| 2023 March | 90 | 20 | 110 |
| 2023 February | 62 | 20 | 82 |
| 2023 January | 62 | 25 | 87 |
| 2022 December | 77 | 30 | 107 |
| 2022 November | 93 | 40 | 133 |
| 2022 October | 102 | 42 | 144 |
| 2022 September | 69 | 27 | 96 |
| 2022 August | 72 | 55 | 127 |
| 2022 July | 53 | 46 | 99 |
| 2022 June | 77 | 47 | 124 |
| 2022 May | 69 | 35 | 104 |
| 2022 April | 89 | 59 | 148 |
| 2022 March | 69 | 44 | 113 |
| 2022 February | 104 | 58 | 162 |
| 2022 January | 91 | 31 | 122 |
| 2021 December | 116 | 39 | 155 |
| 2021 November | 85 | 43 | 128 |
| 2021 October | 68 | 36 | 104 |
| 2021 September | 50 | 38 | 88 |
| 2021 August | 61 | 41 | 102 |
| 2021 July | 72 | 27 | 99 |
| 2021 June | 41 | 28 | 69 |
| 2021 May | 48 | 42 | 90 |
| 2021 April | 115 | 86 | 201 |
| 2021 March | 84 | 35 | 119 |
| 2021 February | 56 | 32 | 88 |
| 2021 January | 41 | 20 | 61 |
| 2020 December | 34 | 12 | 46 |
| 2020 November | 54 | 13 | 67 |
| 2020 October | 44 | 24 | 68 |
| 2020 September | 34 | 25 | 59 |
| 2020 August | 30 | 16 | 46 |
| 2020 July | 39 | 13 | 52 |
| 2020 June | 63 | 17 | 80 |
| 2020 May | 43 | 12 | 55 |
| 2020 April | 33 | 10 | 43 |
| 2020 March | 44 | 5 | 49 |
| 2020 February | 37 | 15 | 52 |
| 2020 January | 44 | 17 | 61 |
| 2019 December | 46 | 26 | 72 |
| 2019 November | 34 | 21 | 55 |
| 2019 October | 45 | 13 | 58 |
| 2019 September | 29 | 14 | 43 |
| 2019 August | 28 | 18 | 46 |
| 2019 July | 37 | 27 | 64 |
| 2019 June | 34 | 26 | 60 |
| 2019 May | 31 | 23 | 54 |
| 2019 April | 54 | 29 | 83 |
| 2019 March | 27 | 24 | 51 |
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