P Randhawa

..No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness...

..In conclusion, serial measurement of viral loads by quantitative PCR is a useful tool in monitoring the course of BK virus infection. The results should be interpreted in conjunction with the clinical picture and biopsy findings...

..Compared with PCR, urine cytology is a less sensitive technique, which requires morphologically intact cells, and cannot distinguish BKV from JC virus...

..Because virus in urine can be derived from the kidneys, ureter, or urinary bladder, we evaluated whether measurement of intrarenal concentrations of viral DNA might serve as a more reliable monitoring tool...

..BKV viremia was seen in kidney but not liver recipients. The mechanisms underlying these notable phenomena remain to be investigated...

..Esterification of cidofovir with hexadecyloxypropyl, octadecyloxyethyl, and oleyloxyethyl groups results in up to a 3-log lowering of the 50% effective concentration and an increased selectivity index...

..T-antigen-specific T-cytotoxic cells circulate in healthy blood donors, implying that transient expression of T antigen presumably occurs at sites of viral latency and helps maintain a constant pool of circulating CD8+ T memory cells...

..This is followed by a discussion of clinical features, laboratory monitoring and therapeutic strategies. Finally, we present potential cellular mechanisms that explain the basis of virus-mediated damage to the human kidney...

..In conclusion, measurement of anti-BKV antibody titer and class response can be used to detect the onset of viral replication. ELISAs can be quite specific despite considerable sequence homology between BK virus and JC virus...

..25; P = 0.05). In summary, serial measurements of anti-BKV immunoglobulin class (i) detect onset of viral replication, (ii) document episodes of seroreversion, and (iii) can potentially provide prognostic information...

..We hypothesized that DNA sequence variations in this region play a role in the pathogenesis of BK virus allograft nephropathy (BKVAN)...

..Rejection may be treated even if EBV is concurrently present. Long-term graft is suboptimal, because low immunosuppression results in a tendency to develop chronic rejection...

..Quantitative polymerase chain reaction (PCR) assay for renal biopsy has not been evaluated as a diagnostic test. Determination of renal BKV load may identify patients at risk for disease before histologic nephropathy...

..In addition to its role in establishing the primary diagnosis, a biopsy can grade the severity of pathology present, help determine the most appropriate therapy, and provide information relevant to graft prognosis...

..This study sought to determine whether analogous viral genetic changes occur in human BK virus (BKV) interstitial nephritis (ISN)...

..Polyoma virus nephropathy after transplantation is believed to be primarily due to the BK virus. We hypothesized that some cases may be associated with the JC polyoma virus (JCV), which is also known to be latent in the kidney...

..4% remained steroid-free from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3-year efficacy of this approach...

..This suggests that the true incidence of rejection may be higher than is clinically appreciated...

..5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach...

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..The proposal is not superior to existing schemas that include assessment of inflammation, which is a well-known prognostic marker in other renal allograft diseases...

..Physicians need to be cognizant of these effects when interpreting the results of quantitative PCR testing in transplant recipients, particularly if there is a discrepancy between the clinical impression and the measured viral load...

..Simian 40 polyomavirus was not identified in any case. These observations may have pathogenic relevance to the development of an extremely refractory form of polyomavirus interstitial nephritis seen after kidney transplantation...

..The Banff schema is the internationally accepted standard for grading acute liver-allograft rejection, but it has not been prospectively tested...

..Within the viruria group, lower ICF values were associated with higher urinary viral load (P= .037). These results show that a decreased ICF test result correlates with active viral replication in kidney transplant recipients...

..Cross reactivity of appropriately selected BKV primers with JCV and SV40 sequences available in current databases was not a significant problem...

..In conclusion, grading of glomerulitis is a meaningful exercise, and a quantification system based on percentage of glomerular involvement shows the most robust associations with clinical parameters and prognosis...

..The incidence of new-onset posttransplantation insulin-dependent diabetes was 0.5%. At current follow-up, the use of Campath 1H rather than thymoglobulin for pretreatment seems to have significantly improved the efficacy of our regimen...

..CONCLUSIONS: IVIG rescue therapy for steroid- or antilymphocyte antibody-resistant rejection is associated with resolution or improvement of rejection severity, stable renal function, and reasonable graft survival...

..Finally, C4d deposits preferentially in lesions of chronic transplant glomerulopathy and arteriolar hyalinosis...

..Further study in late biopsies and other tissue markers of liver AMR with simultaneous DSA measurements are needed...

..However, this lesion frequently coexists with changes suggestive or diagnostic of acute cellular rejection, and intimal arteritis may be seen concurrently in up to 16% of cases...

..A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions...

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..However, within the kidney transplant population, BKV strains derived from patients with asymptomatic viruria did not show complete separation from strains associated with allograft nephropathy...

..Campath was the more effective agent for pretreatment. Guidelines for spaced weaning need additional refinement...

..The association of circulating donor-specific antibody (DSA) strength with crossmatch results is of potential interest to predict allograft outcome...

..A subset of biopsies with BK nephropathy shows tubular basement membrane C4d staining, which correlates with marked viral cytopathic effect...

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..In vitro studies demonstrated slight antiviral activity for chloroquine and nystatin. A sialic acid derivative, BTB11968, was identified as a lead compound for further development...

..The primary goal of this study was to develop a histologic grading system for the diagnosis of small bowel allograft acute rejection...

..This study documents the effectiveness of cold HeLP as a flushing and short-term preservation fluid for living donor kidney transplantation with excellent results and significant cost benefit because of its low cost...

..This study evaluated the incidence of UTI in biopsies with concurrent neutrophilic tubulitis and PTC C4d staining...

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..We aimed to apply these principles in recipients of renal and extrarenal organ transplants...

..3+/-11.7, and 2.3+/-0.8 microg/mL. CONCLUSIONS: The in vitro activity of Cidofovir and Leflunomide is modest, and the selectivity index is low. There is a need to develop more effective and less toxic anti-BK virus drugs for clinical use...

..These cases exemplify the rationale for all patients to be monitored for DSA post-transplantation, with the frequency adjusted based on the individual risk for AMR...

..7 and JC-7.9) and two of 13 SV40 antibodies (VP1-H2 and VP1-I2) recognized linear buried epitopes common to all three viruses and (iii) SV40 antibody VP1-E5 recognized a linear surface epitope on JCV pseudocapsids...

..08) and with significant development of viremia after antirejection treatment (5/9 [56%] versus 0/24 [0%] in patients with low VL, P < .001)...

..We propose that HLA mismatching promotes the development of BKV nephropathy through rejection-related inflammatory processes and heavy immunosuppression which cause virus reactivation and injury of the tubular epithelium...

..Vascular thrombosis, severe glomerular ischemic collapse, and peritubular capillary C4d deposits in scleroderma renal crisis kidney biopsies correlated with increased risk of failure to recover renal function...

..It provides also opportunities for determining the relative immunogenicity of mismatched triplets...

..Interstrain genetic recombination between distant loci in the VP1 and LTA areas is not a common event...

..Pilot screening of 300 compounds from the Tim Tec ActiTarg K library identified a compound, STO18584, with selectivity index of 19.2...

..Finally, we present biochemical mechanisms that could potentially explain several key elements of tissue pathology characteristic of BKV mediated damage to human kidney...

..Clinical syndromes related to polyomavirus infection are summarized in the present review, and strategies for the management of patients who receive transplants are discussed...

..Focal PTC C4d staining in acute renal allograft rejection has not been studied extensively...

..Two biopsies showed electron-dense deposits on ultrastructural examination, but a cause and effect relationship to BK virus infection could not be established...

..0001). Donor vascular disease is an independent risk factor for suboptimal graft survival. Great caution should be exercised in the decision to transplant kidneys with moderate arterial and/or arteriolar luminal narrowing...

..The risk of recurrence does not seem to be increased in comparison with the first graft...

..Lack of parallelism between viral load, tubulitis grade, and serum creatinine illustrates a complex interplay of viral and alloimmune factors leading to graft injury...

..Confirmation by urine culture is needed because biopsies with ischemic injury and acute cellular or antibody-mediated rejection can show overlapping histology...

..The purpose of this work was to perform kidney transplantation under a regimen of immunosuppression that facilitates rather than interferes with the recently defined mechanisms of alloengraftment and acquired tolerance...

..More recently several other agents have also been utilized to treat BKVAN, with variable success. This chapter summarizes the current diagnostic modalities and therapeutic options for BKVAN...

..BK virus is an increasingly recognized pathogen in transplanted patients. DNA sequencing of this virus shows considerable genomic variability...

..Kidney transplant recipients with active BK virus (BKV) replication are generally treated with reduction in immunosuppression to allow a successful immune response against the virus...

..Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning...

..Kidney transplant recipients with BK virus nephropathy or viremia are generally treated with reduction of immunosuppression to facilitate virus eradication...

..Because of the extremely low frequency, interpretation was difficult. Regardless of these results, a more vigorous search for conditions that promote transdifferentiation is warranted...

..Graft failure is significantly associated with donor-derived and early CE. Although its prognosis may be poor in the setting of primary nonfunction, prolonged graft survival may be seen...

..We hypothesize that anti-BKV drugs can be discovered by screening chemical libraries for compounds that can bind to two key viral proteins, namely, viral capsid protein-1 (VP-1) and large T antigen. ..

..This, in turn, will help us to better predict the clinical course of the disease in individual patients, and help devise more effective forms of anti-viral therapy. ..

..We hypothesize that anti-BKV drugs can be discovered by screening chemical libraries for compounds that can bind to two key viral proteins, namely, viral capsid protein-1 (VP-1) and large T antigen. ..

..This, in turn, will help us to better predict the clinical course of the disease in individual patients, and help devise more effective forms of anti-viral therapy. ..

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..This, in turn, will help us to better predict the clinical course of the disease in individual patients, and help devise more effective forms of anti-viral therapy. ..