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  • 1
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    Early allograft inflammation and scarring associate with graft dysfunction and poor outcomes in renal transplant recipients with delayed graft function: a prospective single center cohort study
    Frontiers Media SA ; 2018
    In:  Transplant International Vol. 31, No. 12 ( 2018-12), p. 1369-1379
    Details
    In: Transplant International, Frontiers Media SA, Vol. 31, No. 12 ( 2018-12), p. 1369-1379
    Type of Medium: Online Resource
    ISSN: 0934-0874
    URL: Issue
    URL: Article
    DOI: 10.1111/tri.2018.31.issue-12
    DOI: 10.1111/tri.13318
    Language: English
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 1463183-0
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  • 2
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    Donor acute kidney injury and its effect on 1‐year post‐transplant kidney allograft fibrosis
    Wiley ; 2020
    In:  Clinical Transplantation Vol. 34, No. 2 ( 2020-02)
    Details
    In: Clinical Transplantation, Wiley, Vol. 34, No. 2 ( 2020-02)
    Abstract: Transplantation of kidneys from deceased donors with acute kidney injury (AKI) can expand the donor pool. We investigated the effect of donor AKI on renal function and chronic changes on protocol biopsies at 1‐year post‐transplant. Donor AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. Between 2013 and 2017, 333 kidneys were transplanted and subsequently biopsied after 1 year. Fifty‐three kidneys from AKI donors (AKIN stage I n = 42, stage II n = 8, stage III n = 3) were compared to 280 kidneys from non‐AKI donors. At 1‐year follow‐up, patient and graft survival were comparable. Donor AKI was not predictive of IFTA (Banff interstitial fibrosis plus tubular atrophy scores) at 1‐year post‐transplant biopsy (2.10 ± 1.28 in AKI, 2.09 ± 1.22 in non‐AKI, P  = .95). Donor AKI was also not associated with progression of IFTA from 3 to 12 months ( P  = .69), or inferior glomerular filtration rate (eGFR, P  = .94). In a multivariate analysis, the odds of IFTA 〉 2 were comparable between AKI and non‐AKI groups. In conclusion, the transplantation of kidneys from donors with predominantly stage I AKI results in comparable function and degree of fibrosis on protocol biopsies 1‐year post‐transplant. Selected grafts from donors with AKI are a valuable tool for expanding the donor pool for kidney transplantation.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.v34.2
    DOI: 10.1111/ctr.13770
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 3
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    Pro-inflammatory B Cells Predict Progressive Minimal Early Renal Allograft Inflammation Which Is Associated with Poor Graft Outcomes
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Transplantation Vol. 102, No. Supplement 7 ( 2018-07), p. S28-
    Details
    In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 102, No. Supplement 7 ( 2018-07), p. S28-
    Type of Medium: Online Resource
    ISSN: 0041-1337
    URL: Article
    DOI: 10.1097/01.tp.0000542577.73240.5f
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2035395-9
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  • 4
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    Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation
    Wiley ; 2022
    In:  Clinical Transplantation Vol. 36, No. 4 ( 2022-04)
    Details
    In: Clinical Transplantation, Wiley, Vol. 36, No. 4 ( 2022-04)
    Abstract: Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5–6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R−) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group ( n = 56) received 〈 5 mg/kg ATG and Regular Dose (RD) group ( n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG ( P 〈 .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD ( P = .04) (OR 2.1; 95%CI 1.12–3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.v36.4
    DOI: 10.1111/ctr.14582
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 5
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    Function and longevity of renal grafts from high‐KDPI donors
    Wiley ; 2022
    In:  Clinical Transplantation Vol. 36, No. 9 ( 2022-09)
    Details
    In: Clinical Transplantation, Wiley, Vol. 36, No. 9 ( 2022-09)
    Abstract: High kidney‐donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. Methods We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I‐KDPI ≤ 25% ( n  = 151), Group II‐KDPI 26–50% ( n  = 182), Group III‐KDPI 51–75% ( n  = 176), and Group IV‐KDPI 〉 75% ( n  = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5‐years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group. Findings High‐KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups ( P  = .06). Although patient survival was signigicantly lower for recipients of high‐KDPI grafts, death‐censored graft survival was similar among the four KDPI groups ( P  = .33). Conclusions The shorter functional survival of high‐KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.v36.9
    DOI: 10.1111/ctr.14759
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 6
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    The combination of exposure to Tacrolimus, mycophenolic acid, Inosine 5′‐Monophosphate Dehydrogenase activity and inhibition in the first week define early histological outcomes in renal transplant recipients
    Wiley ; 2022
    In:  Clinical Transplantation Vol. 36, No. 12 ( 2022-12)
    Details
    In: Clinical Transplantation, Wiley, Vol. 36, No. 12 ( 2022-12)
    Abstract: Therapeutic drug monitoring is routine for Tacrolimus, while levels are not routinely monitored for mycophenolic acid (MPA). This study investigated the effect of early post‐transplant pharmacokinetics (PK) of MPA and Tacrolimus along with the pharmacodynamics (PD) of MPA on biopsy‐proven acute rejection (BPAR) after renal transplantation. A prospective PK/PD study with limited sampling (three blood samples) was conducted in renal transplant recipients on week 1, around Day 6 ( n  = 42) and at the 3rd‐month biopsy on Day 90 ( n  = 23). The partial exposures (area under curve [AUC] 0‐3.5 h ) of both MPA and Tacrolimus obtained during the first week were more predictive of rejection (combined clinical and subclinical rejection) by Day 90 than their trough concentrations or Day 90 exposures. Patients with rejection had significantly worse renal function (eGFR) and a comparatively lower exposure to MPA during the first post‐transplant week. The lower MPA exposure was also associated with sub‐optimal inosine monophosphate dehydrogenase (IMPDH) inhibition in patients with rejection, and the probability of rejection was higher in the presence of an increased pre‐transplant IMPDH activity. A composite of parameters, including MPA exposure and IMPDH activity was found to predict acute rejection and may be beneficial along with tacrolimus monitoring early after renal transplantation.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.v36.12
    DOI: 10.1111/ctr.14830
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 7
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    Cross‐species comparison of gene expression between human and porcine tissue, using single microarray platform – preliminary results
    Wiley ; 2004
    In:  Clinical Transplantation Vol. 18, No. s12 ( 2004-08), p. 76-80
    Details
    In: Clinical Transplantation, Wiley, Vol. 18, No. s12 ( 2004-08), p. 76-80
    Abstract: Abstract:  Introduction:  Xenotransplantation is a potential solution for inadequate supply of donor organs. Pigs are considered the ideal donor for kidney transplantation to human recipients, therefore it is important to understand the gene regulation in the porcine organs. Oligonucleotide array technology has been utilized largely for human, mouse and rat gene expression studies only. Its use with porcine genes has not been reported. We investigated the possibility of studying gene regulation in porcine kidney with a human GeneChip microarray ® platform. Methods:  To assess the feasibility of using a single microarrray platform for comparison of expressing data across different species (human and pig), we compared the gene expression profiles of human brain, human kidney and pig kidney using the Affymetrix U‐133 A human GeneChip ® , which contains probes for 22 283 genes. Kidney biopsies from pigs and humans, with normal histology, were used to obtain RNA for porcine and human samples, while a commercially available adult whole cortex total RNA sample (Clontech) was used for the human sample. We assessed the intensity ratio for housekeeping and tissue specific genes. To examine the potential for non‐specific binding to create false positive errors in our data, we compared the expression profiles in our experiments to a number of public databases. Results:  There were approximately the same number of genes expressed at higher levels in the pig kidney as in the human kidney and human brain. The major differences in gene expression were found for genes with tissue specific patterns of expression. Eighty genes were increased in human brain vs. human and pig kidney samples. Two hundred and eighty genes were increased in human and pig kidney vs. human brain samples. Of the top 25 genes increased in pig kidney compared with human brain, we were able to cross‐reference 18 genes to the Unigene and SAGE public databases. We confirmed the expected higher levels of expression in the kidney in 18 genes. Of the top 25 genes increased in human brain vs. pig kidney, we were able to cross‐reference 20 genes to the Unigene and SAGE databases and confirm the expected higher expression levels in brain in 17 genes with three inconclusive genes. Conclusion:  This low level of false positive findings, at this preliminary stage, supports the concept of using human GeneChip® microarray platform to compare gene expression profiles between pig and human tissues in the absence of a porcine microarray platform. Our study opens a new avenue into the analysis of porcine genes relevant to xenotransplantation.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2004.18.issue-s12
    DOI: 10.1111/j.1399-0012.2004.00223.x
    Language: English
    Publisher: Wiley
    Publication Date: 2004
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  • 8
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    Early Effect of the Circular Model of Kidney Allocation in the United States
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the American Society of Nephrology Vol. 34, No. 1 ( 2023-01), p. 26-39
    Details
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 1 ( 2023-01), p. 26-39
    Abstract: To reduce geographic disparities in kidney transplantation, the United States implemented a new model of deceased donor kidney allocation in March 2021. The new model’s effect on transplant logistics and kidney utilization is unknown. Using data from the Scientific Registry of Transplant Recipients, this study found an increase in transplants among highly sensitized patients and patients with long dialysis duration. However, cold ischemia time after implementation of the new allocation policy increased significantly, with a suggestion of an increase in kidney discards. Given that the policy was implemented during the coronavirus disease 2019 pandemic, which also affected transplant practices, there is need for continued monitoring for potential unintended consequences of the new policy, along with efforts to mitigate them. Background In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. Methods We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after the onset of COVID-19 and the implementation of KAS250 were evaluated using an interrupted time-series model. Changes in allocation practices (biopsy, machine perfusion, and virtual cross-match) were also evaluated. Results Post-KAS250 saw a two-fold increase in kidneys imported from nonlocal organ procurement organizations (OPO) and a higher proportion of recipients with calculated panel reactive antibody (cPRA) 81%–98% (12% versus 8%; P 〈 0.001) and those with 〉 5 years of pretransplant dialysis (35% versus 33%; P 〈 0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards after KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased, whereas reliance on virtual cross-match increased, which was associated with shorter CIT. Conclusions Early trends after KAS250 show an increase in transplant access to patients with cPRA 〉 80% and those with longer dialysis duration, but this was accompanied by an increase in CIT and a suggestion of worsening kidney discards.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    URL: Article
    DOI: 10.1681/ASN.2022040471
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2029124-3
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  • 9
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    Outcomes and factors leading to graft failure in kidney transplants from deceased donors with acute kidney injury—A retrospective cohort study
    Public Library of Science (PLoS) ; 2021
    In:  PLOS ONE Vol. 16, No. 8 ( 2021-8-26), p. e0254115-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 8 ( 2021-8-26), p. e0254115-
    Abstract: Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0254115
    DOI: 10.1371/journal.pone.0254115.g001
    DOI: 10.1371/journal.pone.0254115.t001
    DOI: 10.1371/journal.pone.0254115.t002
    DOI: 10.1371/journal.pone.0254115.t003
    DOI: 10.1371/journal.pone.0254115.t004
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2021
    detail.hit.zdb_id: 2267670-3
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  • 10
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    High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Transplantation Direct Vol. 5, No. 2 ( 2019-2), p. e424-
    Details
    In: Transplantation Direct, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 2 ( 2019-2), p. e424-
    Abstract: High calcineurin inhibitor (CNI) intrapatient variability (IPV) has been associated with poor kidney allograft outcomes. However, the relationship between early allograft histological changes, their progression, and CNI-IPV is less well studied. Hence, we evaluated effect of CNI-IPV defined by the degree of fluctuation of CNI levels in all kidney transplant patients over 2 to 12 months posttransplant on early allograft inflammation, subsequent chronicity, and later clinical outcomes. Methods Two hundred eighty-six patients transplanted from January 2013 to November 2014 were enrolled with protocol and indication biopsies. The mean CNI-IPV was 28.5% and a quarter of our cohort had IPV of 35% or greater (high CNI IPV). Baseline demographic differences were similar between high and low CNI IPV groups. Results High CNI-IPV was associated with a higher incidence of acute rejection (AR) within 1 year (52% vs 31% P 〈 0.001), more persistent/recurrent AR by 1 year (18.2% vs 6.2%, P = 0.002), higher-grade AR (≥Banff 1B, 27.5% vs 7.3%, P 〈 0.001), and worse interstitial fibrosis/tubular atrophy ( P = 0.005). High CNI-IPV was associated with increased graft loss (GL) and impending graft loss (iGL, defined as eGFR 〈 30 ml/min and 〉 30% decline in eGFR from baseline), regardless of donor-specific antibody, delayed graft function, rejection, or race. In a multivariate Cox Proportional Hazards Model, high CNI-IPV was independently associated with GL + iGL (hazard ratio, 3.1; 95% confidence interval, 1.6–5.9, P 〈 0.001). Conclusions High CNI-IPV within 1 year posttransplant is associated with higher incidence of AR, severe AR, allograft chronicity, GL, and iGL. This represents a subset of patients who are at risk for poor kidney transplant outcomes and potentially a modifiable risk factor for late allograft loss.
    Type of Medium: Online Resource
    ISSN: 2373-8731
    URL: Article
    DOI: 10.1097/TXD.0000000000000862
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2890276-2
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