Dataset Information

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

ABSTRACT:

Background and objectives

BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.

Design, setting, participants, & measurements

We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database.

Results

The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95).

Conclusions

In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV.

Podcast

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.

SUBMITTER: Hall IE

PROVIDER: S-EPMC8259491 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

Hall Isaac E IE Reese Peter Philip PP Reese Peter Philip PP Mansour Sherry G SG Mohan Sumit S Jia Yaqi Y Thiessen-Philbrook Heather R HR Brennan Daniel C DC Doshi Mona D MD Muthukumar Thangamani T Akalin Enver E Harhay Meera Nair MN Schröppel Bernd B Singh Pooja P Weng Francis L FL Bromberg Jonathan S JS Parikh Chirag R CR

Clinical journal of the American Society of Nephrology : CJASN 20210310 5

<h4>Background and objectives</h4>BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.<h4>Design, setting, participants, & measurements</h4>We studied 1025 kidney recipients from 801 deceased donors transplante ...[more]

PMID: 33692117

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Project description:Rationale & objectiveDonor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation.Study designProspective cohort.Setting & participants862 deceased donors for 1,137 kidney recipients at 13 centers.ExposuresWe measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI.OutcomesThe primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year.Analytical approachMultivariable Fine-Gray models with death as a competing risk.ResultsMean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA.LimitationsBPAR was ascertained through for-cause biopsies, not surveillance biopsies.ConclusionsIn a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.

Project description:Socioeconomically deprived individuals with renal disease are less likely to receive a live-donor kidney transplant than less-deprived individuals. This qualitative study aimed to identify reasons for the observed socioeconomic disparity in live-donor kidney transplantation.A qualitative study using face-to-face in-depth semistructured interviews.A UK tertiary renal referral hospital and transplant centre.Purposive sampling was used to select deceased-donor transplant recipients from areas of high socioeconomic deprivation (SED) (19 participants), followed by a low SED comparison group (13 participants), aiming for maximum diversity in terms of age, gender, ethnicity, primary renal disease and previous renal replacement therapy.Participants were interviewed following their routine transplant clinic review. Interviews were digitally audio-recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using the constant comparison method described in Grounded Theory.Themes common and distinct to each socioeconomic group emerged. 6 themes appeared to distinguish between individuals from areas of high and low SED. 4 themes were distinct to participants from areas of high SED: (1) Passivity, (2) Disempowerment, (3) Lack of social support and (4) Short-term focus. 2 themes were distinct to the low SED group: (1) Financial concerns and (2) Location of donor.Several of the emerging themes from the high SED individuals relate to an individual's lack of confidence and skill in managing their health and healthcare; themes that are in keeping with low levels of patient activation. Inadequate empowerment of socioeconomically deprived individuals by healthcare practitioners was also described. Financial concerns did not emerge as a barrier from interviews with the high SED group. Interventions aiming to redress the observed socioeconomic inequity should be targeted at both patients and clinical teams to increase empowerment and ensure shared decision-making.

Dataset Information

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Podcast

Publications

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

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