#77: Impact of Targeted Tacrolimus Levels on BK Polyomavirus DNAemia Among Pediatric Kidney Transplant Recipients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
I Yildirim ◽  
R Liverman ◽  
S Serluco ◽  
R George ◽  
R Garro ◽  
...  

Abstract Background Uncontrolled BK Polyomavirus (BK) DNAemia in kidney transplant recipients is a significant cause of allograft dysfunction that can lead to BK Polyomavirus-associated nephropathy with permanent damage and graft loss. BK virus DNAemia can occur early (within the first year) or late (after the first year) following a kidney transplant in children. Prospective monitoring for BK viremia with pre-emptive lowering of immunosuppression has been suggested as an effective approach to prevent BK nephropathy. We evaluated the impact of changes in targeted tacrolimus levels on the incidence of BK DNAemia early post-transplant. Methods In response to a cluster of early-onset BK virus DNAemia cases in the first quarter of 2015, we pursued a quality improvement study to determine whether changes to tacrolimus trough targets for the first 100 days post-transplant would reduce the incidence and severity of BK DNAemia. Targeted tacrolimus levels were decreased by approximately 25% (see Table) and patients receiving transplant from March 20, 2015, and December 31, 2018, were prospectively monitored. The incidence rates of BK DNAemia detected on monthly surveillance testing in the first-year post-transplant were compared for patients transplanted between January 1, 2013, and March 14, 2015 (pre-intervention) and March 15, 2015, to December 31, 2018 (post-intervention). Results Of 148 children who received kidney transplants during the study period, 52 (35%) were transplanted in the pre-intervention era and 96(65%) were transplanted during the post-intervention era. The median age at transplant was 13.9 years [interquartile range (IQR) 8.0–16.7 years]. Age at transplant, gender (overall 55% male), and race (overall 54% White, 35% Black) was not significantly different between the cohorts. The risk of early-onset BK DNAemia within the first 100 days post-transplant was 19 per 100 patients in the pre-intervention cohort and 13 per 100 patients in the post-intervention cohort, corresponding to a 35% reduction after lowering targeted tacrolimus levels. The median time to first detected BK DNAemia increased from 77 days (IQR 45–90 days) in pre-intervention to 104 days (IQR 47–174 days) in the post-intervention cohort. Conclusions BK DNAemia heralds a serious complication of kidney transplantation and may represent over immunosuppression and increased risk for other infectious complications. We were able to reduce the rate of early-onset BK DNAemia by reducing tacrolimus target levels in the first 12 weeks post-transplant. Preventing early uncontrolled viremia may decrease the need for immunosuppression reduction which increases the risk for rejection.

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.


2017 ◽  
Vol 19 (3) ◽  
pp. e12681 ◽  
Author(s):  
Marie-Christine Simard-Meilleur ◽  
Paule Bodson-Clermont ◽  
Gilles St-Louis ◽  
Michel R. Pâquet ◽  
Catherine Girardin ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
David Arroyo ◽  
Sindhu Chandran ◽  
Parsia A. Vagefi ◽  
David Wojciechowski

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center’s experience with the use of ciprofloxacin in patients with persistent BKV infection.Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin.Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment.Conclusion.Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy.


2020 ◽  
Author(s):  
Masoud Khosravi ◽  
Mahlagha Dadras ◽  
Ali Monfared ◽  
Siamak Granmaieh ◽  
Mohammad Shenagari Rashti ◽  
...  

Abstract Purpose: Polyomavirus nephropathy has been recognized as an important cause of silent loss of kidney transplant function in 3-5% of kidney transplant recipients. We evaluate the risk factors associated with BK virus infection in our kidney transplant recipients.Materials and Methods: We collected clinical information, urinary Decoy cell, and blood PCR tests for polyomavirus infection in our 223 kidney transplant recipients undergoing surgery at Razi hospital at Guilan University of Medical Sciences between 2007 and 2015. In case of high virus count or if plasma creatinine was elevated, a kidney biopsy would be performed. SPSS version 18 were used for analysis of data.Results: Among 223 patients, 116 (52%) were male, 107 females (48%). Mean age of participants were 49.6 years. Of 223 kidney transplant patients enrolled in this study, 41 (18.3%) had viral genome in their urine, and of these 41 patients, 15 persons (6.7%) had viral genome in their blood. Only 3 patients out of 10, have had BK Virus nephropathy in their kidney biopsy. Among risk factors, we found that post-transplant duration, and use of anti-thymocyte globulin, were most significant risk factors for finding Decoy cells in urine of patients (p<0.01).Conclusions: Post-transplant time, specially the first 6 months because of strong immunosuppression, and thereafter, use of anti-thymocyte globulin (for prophylaxis or treatment of rejection) were recognized as most important risk factors for reactivation of polyomavirus infection in our patients. We concluded that kidney transplant recipients should be monitored in episodically after transplant.


2021 ◽  
Vol 1 (2) ◽  
pp. 100-120
Author(s):  
Ellen M. Castle ◽  
Emily McBride ◽  
James Greenwood ◽  
Kate Bramham ◽  
Joseph Chilcot ◽  
...  

Weight gain within the first year of kidney transplantation is associated with adverse outcomes. This narrative systematic review and meta-analysis examines the effect of exercise, physical activity, dietary, and/or combined interventions on body weight and body mass index (BMI) within the first year of kidney transplantation. Seven databases were searched from January 1985 to April 2021 (Prospero ID: CRD42019140865), using a ‘Population, Intervention, Controls, Outcome’ (PICO) framework. The risk-of-bias was assessed by two reviewers. A random-effects meta-analysis was conducted on randomized controlled trials (RCTs) that included post-intervention body weight or BMI values. Of the 1197 articles screened, sixteen met the search criteria. Ten were RCTs, and six were quasi-experimental studies, including a total of 1821 new kidney transplant recipients. The sample sizes ranged from 8 to 452. Interventions (duration and type) were variable. Random-effects meta-analysis revealed no significant difference in post-intervention body weight (−2.5 kg, 95% CI −5.22 to 0.22) or BMI (−0.4 kg/m2, 95% CI −1.33 to 0.54). Despite methodological variance, statistical heterogeneity was not significant. Sensitivity analysis suggests combined interventions warrant further investigation. Five RCTs were classified as ‘high-risk’, one as ‘some-concerns’, and four as ‘low-risk’ for bias. We did not find evidence that dietary, exercise, or combined interventions led to significant changes in body weight or BMI post kidney transplantation. The number and quality of intervention studies are low. Higher quality RCTs are needed to evaluate the immediate and longer-term effects of combined interventions on body weight in new kidney transplant recipients.


2020 ◽  
Vol 3 ◽  
Author(s):  
William Goggins ◽  
Richard Mangus ◽  
Burcin Ekser ◽  
William Goggins

Background:     At the time of kidney transplantation (KT), induction immunosuppression is used to reduce the incidence of early rejection and avoid the use of chronic corticosteroids in maintenance immunosuppression. There is currently no standard of care for induction immunosuppression in the pediatric recipient, instead it is based on institutional preference. In this study, we compare our current induction immunosuppression, rabbit anti-thymocyte globulin (rATG), to our previous induction immunosuppression, Daclizumab in patients under the age of 11.     Methods:     From 07/2004 to 08/2019, 79 patients under the age of 11 have received a KT. 7 patients were excluded from analysis due to Basiliximab induction (n=3), graft loss within 10 days (n=3) and patient death (n=1). 72 patients were analyzed, of which 39 patients (54%) with rATG induction were compared to 33 patients (46%) with daclizumab induction. All patients were maintained on steroid-free immunosuppression regimen after transplant. More than 20 variables were followed, along with rejection, graft failure, and any prevalence of post-transplant lymphoproliferative disorder (PTLD) was recorded (Figure 1).    Results:     Patients demographics were similar in both groups. Graft survival was good and statistically similar up to 5 years. In both groups, serum creatinine levels were similar up to 1 year follow up. Although CMV infection was similar in both groups, BK viremia and BK virus in the urine were more frequent in rATG group. Post-transplant lymphoproliferative disorder was significantly higher in the Daclizumab group (p=0.022), but less acute rejection was observed in the Daclizumab group (Figure 1).     Potential Impact:     Our study suggests that rATG is a safe and effective induction agent in pediatric kidney transplant recipients under the age of 11. Recipients have excellent patient and graft survival. It is associated with strong kidney function and low PTLD. Screening for BK virus in the urine is essential with rATG induction.     Table 1:     Induction Agent  Daclizumab  rATG  p value  Demographics        Number  33  39  N.S.  Sex  15M, 18F  27M, 12F  0.042  Age (years)  5.5 ± 2.7  6.1 ± 2.7  N.S.  Height (m)  1.02 ± 0.23  1.06 ± .21  N.S.  Weight (kg)  18.75 ± 9.93  19.08 ± 6.42  N.S.  Outcomes        Cr 1 month (mg/dL)  0.56 ± .31  0.45 ± .17  0.056  Cr 6 months (mg/dL)  0.54 ± .22  0.52 ± .18  N.S.  Cr 1 year (mg/dL)  0.63 ± .27  0.59 ± .17  N.S.  eGFR 1 month (ml/min/1.73m2)  84.81 ± 27.95  107.08 ± 30.09  0.0019  eGFR 6 months (ml/min/1.73m2)  85.04 ± 27.60  92.48 ± 28.07  N.S.  eGFR 1 year (ml/min/1.73m2)  74.31 ± 26.8  79.3 ± 22.01  N.S.  Rejection 6 months  1 (3.03%)  8 (20.51%)  0.0188  Rejection 1 year  2 (6.06%)  8 (20.51%)  0.0682  Graft Survival 1 year  100% (33/33)  100% (39/39)  N.S.  Graft Survival 3 years  96.97% (32/33)  100% (25/25)  N.S.  Graft Survival 5 years  96.88 (31/32)  100% (22/22)  N.S.  Cases of PTLD  5 (18.18%)  0 (0%)  0.022  Chronic steroid use  2 (6.06%)  2 (5.13%)  N.S.  BK Urine only 1 year  0% (0/33)*  10.26% (4/39)  0.0439  BK Viremia 1 year  3.03% (1/33)*  17.95% (7/39)  0.0356  CMV Viremia 1 year  0% (0/33)  5.13% (2/39)  N.S.  N.S.= Not statistically significant.  *BK screening was not routine during time of daclizumab induction 


2016 ◽  
Vol 82 ◽  
pp. S10-S11
Author(s):  
Antonio Piralla ◽  
Alessia Girello ◽  
Marta Premoli ◽  
Umberto Palatini ◽  
Fausto Baldanti

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