• Users Online: 226
  • Print this page
  • Email this page


 
 
Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 18  |  Issue : 2  |  Page : 97-102

Immunohistochemical evaluation of renal allograft biopsies from a sample of iraqi renal transplant recipients


1 Department of Microbiology, Al-Mustansiriyah College of Medicine, Baghdad, Iraq
2 Department of Histopathology, Al-Yarmouk Teaching Hospital, Baghdad, Iraq

Date of Submission24-May-2019
Date of Acceptance30-Sep-2019
Date of Web Publication18-Dec-2019

Correspondence Address:
Dr. Taha Yaseen Al-Azzawi
No. 50, Street No. 51, Al-Mansour, Baghdad
Iraq
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/MJ.MJ_11_19

Get Permissions

  Abstract 


Context: Renal transplantation is the best treatment for end-stage renal disease, although some complication may arise after transplantation including transplant rejection and infection, each of the two can occur oppositely to the other since the insufficiently suppressed immune system can still attack the graft while excessively suppressed immune system may allow latent virus to reactivate. The best way to diagnose both of the conditions is by immunohistochemical staining using monoclonal antibodies specific for BK virus and C4d. Aims: This study aims to investigate the frequency of antibody-mediated rejection (AMR) and BK virus nephropathy (BKVN) in renal allograft biopsies in Iraq. Settings and Design: The study encompassed 53 renal transplant recipients who developed signs of renal dysfunction. Subjects and Methods: Renal allograft biopsies were collected from centre of nephrology and kidney transplantation and AL-Yarmouk teaching hospital in Baghdad from January to September 2017, biopsies were embedded, sectioned, fixed on slides and stained with hematoxylin and eosin and monoclonal antibodies specific for C4d and BK virus. Statistical Analysis Used: Data were tested using Chi-square test; the analysis was conducted using the available SPSS-24 Package. Results: Samples were obtained from 38 males and 15 females in whom their mean age was 36.0 ± 13.8 years, the average time between transplantation and biopsy was 33.5 ± 22.5 months, and there was 31 donation from related donor and 22 from unrelated donor. The frequency of BKVN was 1.8% and the frequency of AMR was 52%. Conclusions: Using immunostaining of renal allograft biopsies using anti-BKV antibodies and anti-C4d help in identifying the causes of renal impairment after transplantation that otherwise remain hidden.

Keywords: Biopsy, BK virus, rejection, renal, transplant


How to cite this article:
Al-Azzawi TY, Al-Shawk RS, Al-Taee TJ. Immunohistochemical evaluation of renal allograft biopsies from a sample of iraqi renal transplant recipients. Mustansiriya Med J 2019;18:97-102

How to cite this URL:
Al-Azzawi TY, Al-Shawk RS, Al-Taee TJ. Immunohistochemical evaluation of renal allograft biopsies from a sample of iraqi renal transplant recipients. Mustansiriya Med J [serial online] 2019 [cited 2020 Jul 3];18:97-102. Available from: http://www.mmjonweb.org/text.asp?2019/18/2/97/273342




  Introduction Top


Renal transplantation

Renal transplantation is considered the treatment of choice for patients with end-stage renal disease; it is superior to hemodialysis because it lowers mortality rates and reduces the coast of treatment;[1] however, there are a number of complications that can arise after transplantation jeopardizing the survival of the graft, like transplant rejection, in the past decades; there were considerable advances in immunosuppression protocols and compatibility testing which reduced the incidence of rejection to only 10%–15% in the 1st year of transplantation;[2],[3] however, these advances did not come without a cost since restraining the normal immune response leads to the reactivation of latent viruses.[4] Renal transplantation in Iraq begun in 1973, and the first transplant was conducted at Al-Rasheed military hospital; later in 1985, the transplantation team was transferred to Baghdad Medical City in Baghdad and established a renal transplantation unit; in 1990, the transplantation unit became a specialized center.[5]

Rejection

Renal transplant rejection is a serious complication that can arise after renal transplantation, it is an immunological reaction toward the allograft tissue, and both innate and adaptive arms of the immune system participate in this reaction leading to tissue injury that impairs renal functions;[6] in the present, the major cause of graft loss is antibody-mediated rejection (AMR);[7] AMR is classified into hyperacute, acute, and chronic AMR. Hyperacute AMR is may be caused by ABO-incompatible transplantation and may take place directly after transplantation.[8] Acute AMR commonly occur within an extended period of time and usually becomes chronic; first, antidonor antibodies in the recipient serum bind to graft tissue leading to complement fixation; then, glomerular and peritubular capillaries undergo an acute injury, sequentially leading to transplant glomerulopathy and disruption of the tubulointerstitium.[9] Chronic AMR is manifested by a specific morphological changes that are caused by tissue injury, and the word “chronic” is not used to describe the period of time required to develop rejection.[10]

C4d staining

The binding of antidonor that is generated by activated B cells to the renal endothelium activates the classical pathway of complement system; phagocytic cells that possess receptors for complement components bind C3b and C4b on target cells which leads to the destruction of these targets; in addition, free components such as C3a, C4a, and C5a recruit macrophages to the site of complement activation and late components C6, 7, 8, and 9 join together to make membrane attack complex MAC which penetrates cell membrane and causes the cell components to leak out leading to cell death. C4b is further degraded in some cases into smaller fragments like C4d.[11]

C4d is a split complement component that attaches to endothelial cells of peritubular capillaries, and its binding is evident of interaction between complement-fixing antibodies and vascular endothelium. The detection of C4d expression in renal biopsy by methods like immunohistochemistry IHC or immunofluorescence IF is used since 1993 to diagnose AMR;[12],[13] though in the present, AMR is diagnosed in C4d negative as long as there is evidence of microvascular injury and circulating donor-specific antibodies DSA.[14]

BK virus-associated nephropathy

BK virus is a member of Polyomavirus family; it is a small double-stranded DNA virus that can cause a syndrome called BK virus nephropathy (BKVN).[15] BK virus infection occurs as early as 3–4 years of age;[16] after infection, the virus remains latent in the tubular epithelial cells of the kidney;[17] when renal transplant recipients receive immunosuppression, BK virus resumes replication and causes lysis of tubular endothelium.[18]

Despite BK virus infection being mostly asymptomatic in immunocompetent individuals, it is found that up to 5% of healthy population and 60% of immunocompromised patients shed the virus in their urine.[19],[20],[21]

The replicative cycle of BK virus starts as the virions adsorb to target cell surface by an N-linked glycoprotein which acts as a receptor;[22] BK virions enter the target cell by caveolae-mediated endocytosis;[23] the virions are then carried to the nucleus by the cytoskeletal transport machinery; once in the nucleus virions are uncoated and their genomes are transcribed, replicated, and encapsidated to form the new progeny;[24] the reactivation of BK virus in the renal epithelial cells cause shedding of Decoy cells and virions in the urine.[25]

This study was conducted to investigate the frequency of BKVN and AMR in a sample of renal transplant recipients and to show the role of immunohistochemistry in diagnosing posttransplant complications.


  Subjects and Methods Top


We prospectively studied 53 cases of renal allograft biopsies collected from center of nephrology and kidney transplantation and AL-Yarmouk teaching hospital in Baghdad (ethical permission was granted by these institutions) from January to September 2017; baseline characteristics of the patients (age, gender, time between transplantation and biopsy, donor–recipient relation and immunosuppression regimen) were obtained, and consents were signed by all the participants in this research.

Morphologic evaluation of the biopsies was performed using hematoxylin and eosin according to Banff 13 classification [26] in consistence with clinical features of the patients.

Immunohistochemistry procedure

Processing of specimen biopsies was held in Al-Yarmouk teaching hospital laboratories. Paraffin blocks were cut into 4 μ, and sections were placed on positive charged slides, de-paraffinization of slides was done in xylene then the slides were rehydrated in alcohol. For antigen retrieval, slides were immersed in 10 mM sodium citrate buffer (PH = 7.4) and heated to 95°C for 30 min in microwave and to reduce endogenous peroxidase activity; three drops of peroxidase block were added to each section and incubated for 5 min; then, the slides were washed with phosphate buffer saline (PBS) for 2 min. Three drops of serum block were added to each section and incubated for 2 min; the excess serum was removed. Tissue sections were covered with diluted primary antibody specific for BK virus purchased from Santa Cruz, USA and for C4d purchased from Bio SB, USA, and incubated for 2 h; then, the slides were washed with PBS for 2 min. Each tissue section was covered with biotinylated secondary antibody for 30 min and then washed with PBS for 2 min. Sections were incubated with horseradish peroxidase HRP-streptavidin complex for 30 min then washed with PBS for 2 min. Slides were developed using three drops of HRP substrate. Sections were counterstained by hematoxylin for 5–10 s, then immediately rinsed in distilled water. Sections were mounted in DPX medium and covered with coverslips and examined by light microscope. Slides were processed using EnVision staining system purchased from Dako, USA. Data analysis was performed using the available statistical package of Statistical Packages for Social Sciences 24 (SPSS-24) (IBM Crop, Released 2016. IBM SPSS version 24.0, Armonk, NY, Chicago, USA).


  Results Top


Of 53 individuals, 38 were males forming 71.6% while 15 were females (28.4%); the mean age of the individuals is 36.0 ± 13.8 years. Thirty-one individuals received organs from relatives while 22 received organs from unrelated donors. The average time between transplantation and biopsy is 33.5 ± 22.5 months. Histopathological and immunohistochemical findings of the biopsies were as follows: acute AMR 10 cases, nine of them were C4d positive, chronic AMR 18 cases, 17 of them were C4d positive, acute tubular necrosis 13 cases all C4d negative, T-cell-mediated rejection TCMR five cases all C4d negative, calcineurin inhibitor nephrotoxicity six cases all C4d negative and BKVN one case which was also C4d negative [Figure 1]. There is a significant difference (P = 0.0001) between C4d expression and histological diagnosis as shown in [Table 1]. There was no significant association between C4d staining and recipient's age (P = 0.651), gender (P = 0.772), serum creatinine at the time of biopsy (P = 0.771), time after transplantation (P = 0.27), source of organ donation (P = 0.718), and immunosuppressive regimen (P = 0.392) as shown in [Table 2]. Polyoma BK virus was detected in only one patient of 53 [Figure 2]; the patient's characteristics is shown in [Table 3]. The detection method was validated by staining BKV positive control slides using the same antibody and detection kit following the same procedure; the stained slides were positive [Figure 3]. In this study, anti-C4d antibodies were used to investigate the expression of C4d in the renal allograft tissue; to the best of our knowledge, this is also the first study in the country that addresses this issue. Twenty-six of 53 biopsies showed deposition of C4d in the renal tissue [Figure 4]; the expression patterns varied among peritubular, glomerular, and vascular expression.
Figure 1: The association of histological diagnosis with C4d expression

Click here to view
Table 1: The correlation between histopathological diagnosis C4d expressions in the studied cases

Click here to view
Table 2: The association of epidemiological and medical characteristics of the recipients with the histopathological and immunohistochemical findings

Click here to view
Figure 2: A renal allograft biopsy slide (×40) showing brown immunohistochemical positivity for BK virus in nucleus of renal tubule epithelial cells (arrowed)

Click here to view
Table 3: Some epidemiological and medical characteristics of the patient diagnosed with BK virus nephropathy

Click here to view
Figure 3: A positive control slide of renal biopsy (×40) showing brown immunohistochemical positivity for BK virus in nucleus of renal tubule epithelial cells (arrowed)

Click here to view
Figure 4: A renal allograft biopsy slide (×40) showing brown immunohistochemical positivity for C4d (Arrowed) in peritubular capillaries

Click here to view



  Discussion Top


At present, dialysis and symptomatic treatment are the major treatments for renal failure; however, renal transplantation is considered the best choice for patients in the end stage of the disease;[27] transplant recipients in the present receive either too much or too little immunosuppression, which expose them to malignancies, drug toxicity and infection, or possibility of rejection;[28],[29] the restriction of the immune system made it possible for latent viruses to reactivate and resume their replication causing damage no less than that of rejection.[30],[31] One of these infections is caused by BK virus which is the etiological agent for BKVN, a syndrome characterized by necrosis of the tubular endothelium leading to impairment of tubular reabsorption; currently, there is no specific treatment for BKVN except for reducing immunosuppression, risking the reoccurrence of rejection.[32] Hence, it is crucial for the survival of the kidney and the patient to precisely identify the cause of renal dysfunction.

The gold standard for the diagnosis of BKVN is the detection of BK virus antigens in renal biopsies.[33],[34] The characteristic features of BKVN are necrosis of tubular epithelial cells, sloughing of cells that bear inclusion from the basement of tubules and infiltrates of plasma cells and lymphocytes such making it resemble features of cellular rejection, so the correct diagnosis depends on immunohistochemical staining.[35],[36],[37]

BKVN is prevalent in 1%–10% of renal transplant recipients;[38] in a study done in China, only 9 positive cases were detected by immunofluorescence of 121 biopsy (7.4%),[39] while in Germany, a research team examined 352 biopsies by immunohistochemical staining only to record 22 cases (6.2%),[40] and even less number of cases were recorded by Mengel et al. using immunohistochemical staining in 1276; only 11 cases were positive for BK virus (>1%).[41]

In Iraq, two studies have been conducted to investigate BK virus infection in renal transplant recipients; one of them detected Decoy cells in urine by  Pap smear More Details method in 27.3% of study participants;[42] the other detected BK viruria by PCR in 2.1% of study participants;[43] to the best of our knowledge, there have not been an attempt to detect neither BK viremia nor BK proved by biopsy.

The rejection of transplanted organs is complicated process involving humoral and cellular pathways which cause a wide range of graft injuries if not managed eventually leading to graft loss,[44] in Iraq; according to the most recent study that investigated survival of renal transplant recipients, incidence of rejection in the 1st year of transplantation was 16.3%, AMR formed 15% of this proportion [5] however these cases are only diagnosed on bases of histological evidence of tissue injury.

Banff 2013 classification of renal allograft biopsies stated that three features must be present in renal allograft biopsy to be diagnosed as acute or chronic AMR:

  1. Histologic evidence of tissue injury
  2. Evidence of antibody interaction with vascular endothelium
  3. Presence of circulating DSA in recipient serum.[14]


C4d is an important marker of AMR that indicates an interaction of antibodies with vascular endothelium and such can be used as evidence of rejection.[12]

Since 1973, hundreds of transplantations were performed in Iraq; however, to this date, the evaluation of renal allograft biopsies is done only on the basis of histopathological characteristics of the specimens due to unavailability of required immunohistochemical markers, and very few studies were conducted about BK polyomavirus infection and less about transplant rejection, and for the best of our knowledge, this is the first study in the country to discuss both of the individuals.

Donor-specific antibodies can produce a damage to the graft tissue by two pathways; indirect pathway by initiation of complement fixation leading to the deposition of C4d and direct pathway by adsorbing to inflammatory cells like neutrophils natural killer cells and macrophages; this pathway, however, does not involve complement fixation so that no C4d will be deposited.[45]

In this study, according to the results obtained by histological diagnosis, 28 of 53 biopsies were diagnosed as AMR; 26 of those were confirmed by C4d staining, and the remaining two lacked C4d expression; it is possible that the injury occurred in these two cases was mediated by inflammatory cells rather than complement fixation.

We aimed by conducting this study to evaluate a sample of renal allograft biopsies using immunohistochemical markers for AMR and BKVN; one limitation of the study is the small sample size; the other is the unavailability of DSA detection methods which could be useful in measuring C4d sensitivity.

Only one case of BKVN was diagnosed in this study making the frequency 1.8% which corresponds with the global frequency rates;[46] the diagnosed case is a male who received Tacrolimus as an immunosuppressant; both are risk factors for BKVN; factors also include old age, episodes of rejection, and cold ischemia time, although the detected case is 27 years of age, with no history of rejection and received the kidney from a living donor.[47],[48]

We also found that 52% of the examined biopsies showed evidence of acute and chronic AMR based on histopathological features and C4d immunostaining; in the absence of DSA screening technology, the frequency could be higher.


  Conclusions Top


The frequency of BKVN in the studied cases is 1.8% which corresponds with the global frequency. C4d helped in reaching diagnosis in approximately half the studied cases. AMR was diagnosed in more than half the studied cases, thereby the immunohistochemical staining of renal allograft biopsies using anti-BKV and anti-C4d Abs is important for the diagnosis of complications that arise after transplantation; in the absence of such method, the accurate diagnosis can be missed and posttransplant complications may be poorly managed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Schnuelle P, Lorenz D, Trede M, Van Der Woude FJ. Impact of renal cadaveric transplantation on survival in end-stage renal failure: Evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. J Am Soc Nephrol 1998;9:2135-41.  Back to cited text no. 1
    
2.
Kuo HT, Sampaio MS, Vincenti F, Bunnapradist S. Associations of pretransplant diabetes mellitus, new-onset diabetes after transplant, and acute rejection with transplant outcomes: An analysis of the organ procurement and transplant network/United network for organ sharing (OPTN/UNOS) database. Am J Kidney Dis 2010;56:1127-39.  Back to cited text no. 2
    
3.
Dunn TB, Noreen H, Gillingham K, Maurer D, Ozturk OG, Pruett TL, et al. Revisiting traditional risk factors for rejection and graft loss after kidney transplantation. Am J Transplant 2011;11:2132-43.  Back to cited text no. 3
    
4.
Alangaden GJ, Thyagarajan R, Gruber SA, Morawski K, Garnick J, El-Amm JM, et al. Infectious complications after kidney transplantation: Current epidemiology and associated risk factors. Clin Transplant 2006;20:401-9.  Back to cited text no. 4
    
5.
Ali AA, Al-Saedi AJ, Al-Mudhaffer AJ, Al-Taee KH. Five years renal transplantation data: Single-center experience from Iraq. Saudi J Kidney Dis Transpl 2016;27:341-7.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Wood KJ, Goto R. Mechanisms of rejection: Current perspective. J Transplant 2011;11:693-7.  Back to cited text no. 6
    
7.
Sellarés J, Reeve J, Loupy A, Mengel M, Sis B, Skene A, et al. Molecular diagnosis of antibody-mediated rejection in human kidney transplants. Am J Transplant 2013;13:971-83.  Back to cited text no. 7
    
8.
Puttarajappa C, Shapiro R, Tan HT. Antibody-mediated rejection: A review. J Transplant 2012;4:143-52.  Back to cited text no. 8
    
9.
Willicombe M, Roufosse C, Brookes P, McLean AG, Galliford J, Cairns T, et al. Acute cellular rejection: Impact of donor-specific antibodies and C4d. Transplantation 2014;97:433-9.  Back to cited text no. 9
    
10.
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: Updates and future directions. Am J Transplant 2008;8:753-60.  Back to cited text no. 10
    
11.
Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med 2010;363:1451-62.  Back to cited text no. 11
    
12.
Djamali A, Kaufman DB, Ellis TM, Zhong W, Matas A, Samaniego M. Diagnosis and management of antibody-mediated rejection: Current status and novel approaches. Am J Transplant 2014;14:255-71.  Back to cited text no. 12
    
13.
Kikić Ž, Kainz A, Kozakowski N, Oberbauer R, Regele H, Bond G, et al. Capillary C4d and kidney allograft outcome in relation to morphologic lesions suggestive of antibody-mediated rejection. Clin J Am Soc Nephrol 2015;10:1435-43.  Back to cited text no. 13
    
14.
Haas M. Pathology of C4d-negative antibody-mediated rejection in renal allografts. Curr Opin Organ Transplant 2013;18:319-26.  Back to cited text no. 14
    
15.
Tremolada S, Akan S, Otte J, Khalili K, Ferrante P, Chaudhury PR, et al. Rare subtypes of BK virus are viable and frequently detected in renal transplant recipients with BK virus-associated nephropathy. Virology 2010;404:312-8.  Back to cited text no. 15
    
16.
Shah KV, Daniel RW, Warszawski RM. High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland. J Infect Dis 1973;128:784-7.  Back to cited text no. 16
    
17.
Shinohara T, Matsuda M, Cheng SH, Marshall J, Fujita M, Nagashima K. BK virus infection of the human urinary tract. J Med Virol 1993;41:301-5.  Back to cited text no. 17
    
18.
Pavlakis M, Haririan A, Klassen DK. BK virus infection after non-renal transplantation. Adv Exp Med Biol 2006;577:185-9.  Back to cited text no. 18
    
19.
Arthur RR, Shah KV. Occurrence and significance of papovaviruses BK and JC in the urine. Prog Med Virol 1989;36:42-61.  Back to cited text no. 19
    
20.
Jin L, Pietropaolo V, Booth JC, Ward KH, Brown DW. Prevalence and distribution of BK virus subtypes in healthy people and immunocompromised patients detected by PCR-restriction enzyme analysis. Clin Diagn Virol 1995;3:285-95.  Back to cited text no. 20
    
21.
Hirsch HH. BK virus: Opportunity makes a pathogen. Clin Infect Dis 2005;41:354-60.  Back to cited text no. 21
    
22.
Dugan AS, Eash S, Atwood WJ. An N-linked glycoprotein with alpha (2,3)-linked sialic acid is a receptor for BK virus. J Virol 2005;79:14442-5.  Back to cited text no. 22
    
23.
Eash S, Querbes W, Atwood WJ. Infection of vero cells by BK virus is dependent on caveolae. J Virol 2004;78:11583-90.  Back to cited text no. 23
    
24.
Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses in human disease. Virology 2009;384:266-73.  Back to cited text no. 24
    
25.
Matłosz B, Durlik M, Wesołowska A, Mróz A, Zegarska J, Rowiński W, et al. Polyoma BK virus reactivation in kidney and pancreas-kidney recipients. Transplant Proc 2005;37:947-8.  Back to cited text no. 25
    
26.
Loupy A, Haas M, Solez K, Racusen L, Glotz D, Seron D, et al. The Banff 2015 kidney meeting report: Current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant 2017;17:28-41.  Back to cited text no. 26
    
27.
Aytekin A, Sahin S, Bekir Hacioglu M, Karatas F, Ince M. Extremely high level of CA 19-9 in a patient with metastatic pancreatic cancer and chronic renal failure- second highest level of CA 19-9 in the literature. J BUON 2015;20:1169-70.  Back to cited text no. 27
    
28.
Ó Broin P, Hayde N, Bao Y, Ye B, Calder RB, de Boccardo G, et al. A pathogenesis-based transcript signature in donor-specific antibody-positive kidney transplant patients with normal biopsies. Genom Data 2014;2:357-60.  Back to cited text no. 28
    
29.
Morath C, Zeier M, Süsal C, Döhler B, Opelz G. Response to A reassessment of the survival advantage of simultaneous kidney-pancreas versus kidney-alone transplantation. Transplantation 2015;99:e175.  Back to cited text no. 29
    
30.
Weikert BC, Blumberg EA. Viral infection after renal transplantation: Surveillance and management. Clin J Am Soc Nephrol 2008;3 Suppl 2:S76-86.  Back to cited text no. 30
    
31.
Karuthu S, Blumberg EA. Common infections in kidney transplant recipients. Clin J Am Soc Nephrol 2012;7:2058-70.  Back to cited text no. 31
    
32.
Al-Raisi F, Mohsin N, Kamble P. Management of BK virus nephropathy in kidney transplant recipients at the royal hospital – Clinical audit - Oman. Exp Clin Transplant 2015;13 Suppl 1:156-8.  Back to cited text no. 32
    
33.
Johne R, Buck CB, Allander T, Atwood WJ, Garcea RL, Imperiale MJ, et al. Taxonomical developments in the family polyomaviridae. Arch Virol 2011;156:1627-34.  Back to cited text no. 33
    
34.
Jamboti JS. BK virus nephropathy in renal transplant recipients. Nephrology (Carlton) 2016;21:647-54.  Back to cited text no. 34
    
35.
Drachenberg CB, Beskow CO, Cangro CB, Bourquin PM, Simsir A, Fink J, et al. Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology. Hum Pathol 1999;30:970-7.  Back to cited text no. 35
    
36.
Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant 2000;15:324-32.  Back to cited text no. 36
    
37.
Ahuja M, Cohen EP, Dayer AM, Kampalath B, Chang CC, Bresnahan BA, et al. Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis. Transplantation 2001;71:896-9.  Back to cited text no. 37
    
38.
Hirsch HH, Snydman DR. (2005) BK virus: Opportunity makes a pathogen. Oxford J Clin Infect Dis 2007;41:354-60.  Back to cited text no. 38
    
39.
Shu-Ming J, Zhi-Hong L, Di W, Ji-Qiu W, Ke-Nan X, Qi-Quan S, et al. Surveillance renal allograft biopsy on diagnosis of BK virus nephropathy in Chinese renal transplant recipients. Open J Organ Transpl Surg 2012;2:62-8.  Back to cited text no. 39
    
40.
Jacobi J, Prignitz A, Büttner M, Korn K, Weidemann A, Hilgers KF, et al. BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition. BMC Nephrol 2013;14:207.  Back to cited text no. 40
    
41.
Mengel M, Marwedel M, Radermacher J, Eden G, Schwarz A, Haller H, et al. Incidence of polyomavirus-nephropathy in renal allografts: Influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003;18:1190-6.  Back to cited text no. 41
    
42.
Al-Obaidi AB, Qasim BJ, Husain AG, Kadhim HS, Habib MA, Abd KH, et al. BK Polyomavirus-infected decoy cells in urine cytology specimens of renal transplant recipients. Iraq J Med Spec 2015;13:70-5.  Back to cited text no. 42
    
43.
Mohammad TS, Dawood DS. Detection of polyomavirus BK and JC in kidney transplant recipients. Iraqi Nat J Nurs Spec 2016;29:106-16.  Back to cited text no. 43
    
44.
Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff '09 meeting report: Antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 2010;10:464-71.  Back to cited text no. 44
    
45.
Farkash EA, Colvin RB. Diagnostic challenges in chronic antibody-mediated rejection. Nat Rev Nephrol 2012;8:255-7.  Back to cited text no. 45
    
46.
Ramos E, Drachenberg CB, Portocarrero M, Wali R, Klassen DK, Fink JC, et al. BK virus nephropathy diagnosis and treatment: Experience at the university of Maryland renal transplant program. Clin Transpl 2002:143-53.  Back to cited text no. 46
    
47.
Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, et al. Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation 2005;79:1277-86.  Back to cited text no. 47
    
48.
Brennan DC, Agha I, Bohl DL, Schnitzler MA, Hardinger KL, Lockwood M, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-94.  Back to cited text no. 48
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Subjects and Methods
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed458    
    Printed36    
    Emailed0    
    PDF Downloaded44    
    Comments [Add]    

Recommend this journal