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Although she was asymptomatic&#44; her serum creatinine level was increased gradually during last 3&#8211;4 months &#40;from 1&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dl to 1&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#46; Her primary renal disease was unknown&#46; She had been under the treatment of tacrolimus 2<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mg&#44; prednisolone 5<span class="elsevierStyleHsp" style=""></span>mg&#44; mycophenolate sodium 3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>360<span class="elsevierStyleHsp" style=""></span>mg&#46; Physical examination was normal&#46; Serum creatinine was 1&#46;82<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; urine microscopy was normal&#46; 154<span class="elsevierStyleHsp" style=""></span>mg&#47;day proteinuria was obtained&#46; ANA was positive&#44; though ENA was negative&#46; Anti CMV IgM was negative&#44; whereas serum BK&#47;JC PCR was positive&#46; Serum tacrolimus level was 9&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Transplant renal doppler ultrasonography revealed normal findings&#46; Renal biopsy was performed&#46; Intranuclear inclusions&#44; cytoplasmic and nuclear enlargement in tubular epithelial cells and tubular necrosis were seen on light microscopy&#46; These biopsy findings might suggest viral infection of the renal allograft&#46; Immunohistochemical analysis of the renal biopsy for CMV was negative&#44; but study with SV40 antigen could not be performed as it was not available in our center&#46; Intranuclear spherical viral particles were seen in some tubular epithelial cells on EM &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Viral particles were in paracrystalline structure and about 30<span class="elsevierStyleHsp" style=""></span>nm in diameter&#46; They were differentiated from inclusions of adenovirus with 80&#8211;100<span class="elsevierStyleHsp" style=""></span>nm in diameter &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Finally&#44; BKVN was diagnosed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">BKVN is one of the well-known reasons of morbidity in renal transplant patients&#46; It occurs with a prevalence of 1&#8211;10&#37; in renal transplant patients and graft loss is up to 80&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> BKVN occurs mostly during the first year after transplantation and it is characterized only by deterioration of renal functions&#44; usually without any symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Early diagnosis is important to prevent allograft dysfunction in kidney transplant patients&#46; Our patient was also declared no symptoms&#44; but only a gradual increase in serum creatinine was observed in the second year of follow up&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The pathogenesis of BKVN is characterized by high grade BKV replication in renal-tubular epithelial cells of renal allograft&#46; Necrosis of tubular cells let BKV leak into the tissue and blood&#44; and then inflammatory cell infiltration to interstitium occurs&#46; This leads to tubular atrophy&#44; interstitial fibrosis and therefore impaired graft function&#46; Intensive immunosuppressive therapy is the leading risk factor in the development of BKVN&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Plasma and urine polymerase chain reaction &#40;PCR&#41;&#44; urine cytology&#44; and urine electron microscopy &#40;EM&#41; can be performed in diagnosis of BKVN whereas renal biopsy is the gold standard method&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;5</span></a> Multiple biopsy should be performed because of multi-focal involvement to prevent sampling errors and biopsy specimen should contain medullary parenchyma as the virus is more likely to present in the medulla&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Intranuclear inclusions&#44; lysis or necrosis of tubular cells showing tubulointerstitial inflammation could be observed on light microscopy&#46; However&#44; changes observed during light microscopy are not pathognomonic for BKVN&#46; Immunohistochemistry &#40;SV40 staining&#41; and EM should be performed&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Herpes simplex virus&#44; adenovirus&#44; CMV&#44; Epstein&#8211;Barr virus &#40;EBV&#41; should also be considered in differential diagnosis as they may cause similar histologic findings&#46; Immunohistochemistry and EM can be helpful in differential diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;8</span></a> Viral particles of BKV are characteristically 30&#8211;50<span class="elsevierStyleHsp" style=""></span>nm in diameter and occasionally form crystalloid structures&#44; whereas inclusions due to family of herpesviridae &#40;including Herpes simplex&#44; EBV and CMV&#41; and adenoviruses are bigger in size &#40;120&#8211;150<span class="elsevierStyleHsp" style=""></span>nm and 70&#8211;90<span class="elsevierStyleHsp" style=""></span>nm respectively&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;6&#44;9&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In our patient&#44; size of the viral particles was 30<span class="elsevierStyleHsp" style=""></span>nm in average&#46; Although light microscopic detection of intranuclear inclusions suggested viral infection of renal allograft&#44; it was the EM that defined dimensions of inclusions and helped the diagnosis&#46; In conclusion&#44; EM evaluation of allograft biopsy may be important in the differential diagnosis of different viral infections of allograft&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p></span></span>"
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Letter to the Editor
BK virus nephropathy in a renal transplant patient: Potential role of electron microscopy in diagnosis
Nefropatía por virus BK en un paciente con trasplante renal: Papel potencial de la microscopía electrónica en el diagnóstico
Simge Bardaka,
Corresponding author
bardaksimge@gmail.com

Corresponding author.
, Kenan Turgutalpa, Ebru Ballıb, Banu Coşkun Yılmazb, İclal Gürsesc, Kaan Esend, Serap Demira, Ahmet Kıykıma
a Division of Nephrology, Department of Internal Medicine, School of Medicine, Mersin University, 33079 Mersin, Turkey
b Department of Histology and Embryology, School of Medicine, Mersin University, Turkey
c Department of Pathology, School of Medicine, Mersin University, Turkey
d Department of Radiology, School of Medicine, Mersin University, Turkey
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Although she was asymptomatic&#44; her serum creatinine level was increased gradually during last 3&#8211;4 months &#40;from 1&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dl to 1&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#46; Her primary renal disease was unknown&#46; She had been under the treatment of tacrolimus 2<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mg&#44; prednisolone 5<span class="elsevierStyleHsp" style=""></span>mg&#44; mycophenolate sodium 3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>360<span class="elsevierStyleHsp" style=""></span>mg&#46; Physical examination was normal&#46; Serum creatinine was 1&#46;82<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; urine microscopy was normal&#46; 154<span class="elsevierStyleHsp" style=""></span>mg&#47;day proteinuria was obtained&#46; ANA was positive&#44; though ENA was negative&#46; Anti CMV IgM was negative&#44; whereas serum BK&#47;JC PCR was positive&#46; Serum tacrolimus level was 9&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Transplant renal doppler ultrasonography revealed normal findings&#46; Renal biopsy was performed&#46; Intranuclear inclusions&#44; cytoplasmic and nuclear enlargement in tubular epithelial cells and tubular necrosis were seen on light microscopy&#46; These biopsy findings might suggest viral infection of the renal allograft&#46; Immunohistochemical analysis of the renal biopsy for CMV was negative&#44; but study with SV40 antigen could not be performed as it was not available in our center&#46; Intranuclear spherical viral particles were seen in some tubular epithelial cells on EM &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Viral particles were in paracrystalline structure and about 30<span class="elsevierStyleHsp" style=""></span>nm in diameter&#46; They were differentiated from inclusions of adenovirus with 80&#8211;100<span class="elsevierStyleHsp" style=""></span>nm in diameter &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Finally&#44; BKVN was diagnosed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">BKVN is one of the well-known reasons of morbidity in renal transplant patients&#46; It occurs with a prevalence of 1&#8211;10&#37; in renal transplant patients and graft loss is up to 80&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> BKVN occurs mostly during the first year after transplantation and it is characterized only by deterioration of renal functions&#44; usually without any symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Early diagnosis is important to prevent allograft dysfunction in kidney transplant patients&#46; Our patient was also declared no symptoms&#44; but only a gradual increase in serum creatinine was observed in the second year of follow up&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The pathogenesis of BKVN is characterized by high grade BKV replication in renal-tubular epithelial cells of renal allograft&#46; Necrosis of tubular cells let BKV leak into the tissue and blood&#44; and then inflammatory cell infiltration to interstitium occurs&#46; This leads to tubular atrophy&#44; interstitial fibrosis and therefore impaired graft function&#46; Intensive immunosuppressive therapy is the leading risk factor in the development of BKVN&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Plasma and urine polymerase chain reaction &#40;PCR&#41;&#44; urine cytology&#44; and urine electron microscopy &#40;EM&#41; can be performed in diagnosis of BKVN whereas renal biopsy is the gold standard method&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;5</span></a> Multiple biopsy should be performed because of multi-focal involvement to prevent sampling errors and biopsy specimen should contain medullary parenchyma as the virus is more likely to present in the medulla&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Intranuclear inclusions&#44; lysis or necrosis of tubular cells showing tubulointerstitial inflammation could be observed on light microscopy&#46; However&#44; changes observed during light microscopy are not pathognomonic for BKVN&#46; Immunohistochemistry &#40;SV40 staining&#41; and EM should be performed&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Herpes simplex virus&#44; adenovirus&#44; CMV&#44; Epstein&#8211;Barr virus &#40;EBV&#41; should also be considered in differential diagnosis as they may cause similar histologic findings&#46; Immunohistochemistry and EM can be helpful in differential diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;8</span></a> Viral particles of BKV are characteristically 30&#8211;50<span class="elsevierStyleHsp" style=""></span>nm in diameter and occasionally form crystalloid structures&#44; whereas inclusions due to family of herpesviridae &#40;including Herpes simplex&#44; EBV and CMV&#41; and adenoviruses are bigger in size &#40;120&#8211;150<span class="elsevierStyleHsp" style=""></span>nm and 70&#8211;90<span class="elsevierStyleHsp" style=""></span>nm respectively&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;6&#44;9&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In our patient&#44; size of the viral particles was 30<span class="elsevierStyleHsp" style=""></span>nm in average&#46; Although light microscopic detection of intranuclear inclusions suggested viral infection of renal allograft&#44; it was the EM that defined dimensions of inclusions and helped the diagnosis&#46; In conclusion&#44; EM evaluation of allograft biopsy may be important in the differential diagnosis of different viral infections of allograft&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p></span></span>"
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