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methylprednisolone &#40;250<span class="elsevierStyleHsp" style=""></span>mg&#44; 125<span class="elsevierStyleHsp" style=""></span>mg&#44; 62&#46;5<span class="elsevierStyleHsp" style=""></span>mg on D1&#44; D2 and D3&#44; respectively&#41; followed by prednisolone at a daily dose of 20<span class="elsevierStyleHsp" style=""></span>mg&#44; tacrolimus and mycophenolate de mofetil &#40;1000<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h&#41;&#8212;both started a week before KT&#46; On D7 he referred dysuria and urinalysis revealed leucocyturia which prompted ceftriaxone start&#46; He was discharged on D8 after KT&#44; with a serum creatinine &#40;SCr&#41; level of 1&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and fluctuating tacrolimus through levels between 5&#46;0 and 10&#46;7<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; Maintenance immunosuppression was achieved with tacrolimus &#40;6&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; prednisolone &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; and mycophenolate mofetil &#40;1000<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Additional chemoprophylaxis was completed with cothrimoxazol 480<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">On D17 after KT&#44; the patient presented to the emergency department with fever&#44; diarrhea and renal dysfunction &#40;SCr 2&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; Spot urinalysis documented microscopic hematuria and leucocyturia&#46; Graft doppler ultrasonography was normal&#46; He was diagnosed with pyelonephritis and intravenous ceftriaxone was started&#46; His toddler developed superior respiratory infection a couple days before&#46; Despite the start of antibiotic&#44; fever persisted and SCr level increased up to 2&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Initial blood&#44; stool and urine cultures&#44; as well as blood polymerase chain reaction &#40;PCR&#41; for cytomegalovirus &#40;CMV&#41; and polyomavirus&#44; stool PCR for rotavirus&#44; noravirus&#44; astrovirus and clostridium were negative&#46; On D23&#44; the antibiotic was stopped and an allograft biopsy was performed&#44; revealing interstitial nephritis with granulomatous-like appearance and ground glass tubular epithelial cell nuclei suggesting viral inclusions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Immunoperoxidase stain was negative for polyomavirus and immunofluorescence was negative for C4d&#46; The result of serum&#44; urine and kidney tissue PCR was positive for adenovirus&#46; These findings prompted mycophenolate mofetil withhold plus intravenous ganciclovir &#40;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for 13 days&#41; and intravenous immunoglobulin &#40;IVIG 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for 4 days&#41; start&#46; Fever remitted in four days and allograft function improved &#40;SCr 1&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL on D34 after surgery&#41;&#46; Upgrading dosing of mycophenolate mophetil was slowly introduced two weeks after kidney biopsy and valganciclovir &#40;450<span class="elsevierStyleHsp" style=""></span>mg twice daily&#41; was maintained until serum adenovirus PCR became negative after 54 days of treatment&#46; Allograft function slowly improved and SCr stabilized at 1&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL six months after transplantation&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Native kidneys&#8217; acute interstitial nephritis &#40;AIN&#41; is more commonly associated with drugs&#46; In contrast&#44; drug-induced AIN is rarely reported in kidney grafts&#44; possibly due to the use of corticosteroids in maintenance immunosuppression strategy&#46; Lymphocytic interstitial infiltrates can be observed in any type of acute renal allograft dysfunction&#44; including calcineurin inhibitors nephrotoxicity&#44; acute tubular necrosis and viral infections&#44; as well as in normally functioning renal allografts&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Diagnosis can be challenging as AIN and acute cellular rejection share histological features&#44; namely a primarily composed lymphocyte interstitial infiltrate&#44; with prominent number of eosinophils&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In this case report&#44; patient&#39;s therapy included many potential AIN inducers&#44; such as antibiotics&#44; and tacrolimus fluctuating through levels could portend an acute rejection&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Granulomatous AIN can be found with mycobacterial&#44; fungal&#44; and viral infections&#44; such as adenovirus&#44; human immunodeficiency virus&#44; CMV and polyomavirus&#44; which were all negative in our patient&#44; except for adenovirus&#46; Kidney biopsy in adenovirus infection often shows interstitial nephritis with viral inclusions in tubular epithelial cells&#46; Granulomatous interstitial nephritis with neutrophilic inflammation&#44; red blood cells in tubules&#44; and parenchymal necrosis is also more frequent in adenovirus than polyomavirus or CMV infection&#46;<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&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In this case&#44; the presence of enlarged tubular epithelial cells with groundglass homogenous intranuclear viral inclusions&#44; suggested a viral etiology and the distinctive pattern of granulomatous infiltrate helped discriminate acute rejection from adenovirus infection&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Adenovirus infection in KT recipients should be considered whenever a KT recipient presents with unexplained voiding dysfunction&#44; hematuria&#44; and sterile pyuria&#46; There is uncertainty regarding monitoring of this virus&#44; but early diagnosis with reduction of immunosuppression is essential to virus clearance and allograft function&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Unlike CMV infection&#44; there is no consensual therapeutic approach for AIN associated with adenovirus infection&#46; Treatment strategies are based on case reports and series of cases&#44; which include immunosuppression tapering and specific antiviral therapy&#44; such as IVIG&#44; pulse&#8211;dose steroids&#44; cidofovir&#44; ribavirin or valganciclovir&#44; in varying combinations&#44; with or without reduction in immunosuppression&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a> Given the inherent toxicity associated to most of these drugs&#44; we report the successful treatment of adenovirus-induced AIN with ganciclovir&#44; IVIG&#44; imunossupression reduction and valganciclovir extended treatment&#46;</p></span>"
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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,
Autor para correspondencia
moreira.l.s.carla@gmail.com

Corresponding author at: Serviço de Nefrologia, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal.
, Joana Rochab, Margarida Silvac, Joana Silvad, Manuela Almeidaa, Sofia Pedrosoa, Ramon Vizcaínoc, La Salete Martinsa, Leonídio Diasa, António Castro Henriquesa, António Cabritaa
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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prednisolone &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; and mycophenolate mofetil &#40;1000<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Additional chemoprophylaxis was completed with cothrimoxazol 480<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">On D17 after KT&#44; the patient presented to the emergency department with fever&#44; diarrhea and renal dysfunction &#40;SCr 2&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; Spot urinalysis documented microscopic hematuria and leucocyturia&#46; Graft doppler ultrasonography was normal&#46; He was diagnosed with pyelonephritis and intravenous ceftriaxone was started&#46; His toddler developed superior respiratory infection a couple days before&#46; Despite the start of antibiotic&#44; fever persisted and SCr level increased up to 2&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Initial blood&#44; stool and urine cultures&#44; as well as blood polymerase chain reaction &#40;PCR&#41; for cytomegalovirus &#40;CMV&#41; and polyomavirus&#44; stool PCR for rotavirus&#44; noravirus&#44; astrovirus and clostridium were negative&#46; On D23&#44; the antibiotic was stopped and an allograft biopsy was performed&#44; revealing interstitial nephritis with granulomatous-like appearance and ground glass tubular epithelial cell nuclei suggesting viral inclusions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Immunoperoxidase stain was negative for polyomavirus and immunofluorescence was negative for C4d&#46; The result of serum&#44; urine and kidney tissue PCR was positive for adenovirus&#46; These findings prompted mycophenolate mofetil withhold plus intravenous ganciclovir &#40;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for 13 days&#41; and intravenous immunoglobulin &#40;IVIG 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for 4 days&#41; start&#46; Fever remitted in four days and allograft function improved &#40;SCr 1&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL on D34 after surgery&#41;&#46; Upgrading dosing of mycophenolate mophetil was slowly introduced two weeks after kidney biopsy and valganciclovir &#40;450<span class="elsevierStyleHsp" style=""></span>mg twice daily&#41; was maintained until serum adenovirus PCR became negative after 54 days of treatment&#46; Allograft function slowly improved and SCr stabilized at 1&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL six months after transplantation&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Native kidneys&#8217; acute interstitial nephritis &#40;AIN&#41; is more commonly associated with drugs&#46; In contrast&#44; drug-induced AIN is rarely reported in kidney grafts&#44; possibly due to the use of corticosteroids in maintenance immunosuppression strategy&#46; Lymphocytic interstitial infiltrates can be observed in any type of acute renal allograft dysfunction&#44; including calcineurin inhibitors nephrotoxicity&#44; acute tubular necrosis and viral infections&#44; as well as in normally functioning renal allografts&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Diagnosis can be challenging as AIN and acute cellular rejection share histological features&#44; namely a primarily composed lymphocyte interstitial infiltrate&#44; with prominent number of eosinophils&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In this case report&#44; patient&#39;s therapy included many potential AIN inducers&#44; such as antibiotics&#44; and tacrolimus fluctuating through levels could portend an acute rejection&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Granulomatous AIN can be found with mycobacterial&#44; fungal&#44; and viral infections&#44; such as adenovirus&#44; human immunodeficiency virus&#44; CMV and polyomavirus&#44; which were all negative in our patient&#44; except for adenovirus&#46; Kidney biopsy in adenovirus infection often shows interstitial nephritis with viral inclusions in tubular epithelial cells&#46; Granulomatous interstitial nephritis with neutrophilic inflammation&#44; red blood cells in tubules&#44; and parenchymal necrosis is also more frequent in adenovirus than polyomavirus or CMV infection&#46;<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&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In this case&#44; the presence of enlarged tubular epithelial cells with groundglass homogenous intranuclear viral inclusions&#44; suggested a viral etiology and the distinctive pattern of granulomatous infiltrate helped discriminate acute rejection from adenovirus infection&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Adenovirus infection in KT recipients should be considered whenever a KT recipient presents with unexplained voiding dysfunction&#44; hematuria&#44; and sterile pyuria&#46; There is uncertainty regarding monitoring of this virus&#44; but early diagnosis with reduction of immunosuppression is essential to virus clearance and allograft function&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Unlike CMV infection&#44; there is no consensual therapeutic approach for AIN associated with adenovirus infection&#46; Treatment strategies are based on case reports and series of cases&#44; which include immunosuppression tapering and specific antiviral therapy&#44; such as IVIG&#44; pulse&#8211;dose steroids&#44; cidofovir&#44; ribavirin or valganciclovir&#44; in varying combinations&#44; with or without reduction in immunosuppression&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a> Given the inherent toxicity associated to most of these drugs&#44; we report the successful treatment of adenovirus-induced AIN with ganciclovir&#44; IVIG&#44; imunossupression reduction and valganciclovir extended treatment&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Light microscopy shows &#40;A&#41; interstitial nephritis and ill-defined granuloma formation surrounding tubules &#40;hematoxylin and eosin stain&#59; original magnification&#44; 40&#215;&#41; and &#40;B&#41; intranuclear viral inclusion &#40;hematoxylin and eosin stain&#59; original magnification&#44; 60&#215;&#41;&#46;</p>"
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2018 Septiembre 204 20 224
2018 Agosto 56 17 73
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Idiomas
Nefrología