Histology of Implantation Biopsies and Kidney Allograft Outcomes
Condition: Kidney Graft Dysfunction
Study type: Observational

Summary: 
      The morphology of transplanted kidney is considered to be important for graft outcomes in
      early and late posttransplant period. Individual histological lesions at the time of kidney
      transplantation, such as sclerosis of glomeruli, vascular narrowing and interstitial
      fibrosis, and composite histological lesions, which integrate histopathological findings in
      different compartments, showed association with suboptimal graft outcomes. However there are
      no consistent association between individual or composite lesions and transplant outcomes.
      Some possible explanations for such inconsistent results are non-uniformity in grading
      histological lesions or in defining graft outcomes. Furthermore, studies vary in terms of
      patient selection, and some results are not corrected for covariates. It is also unclear,
      whether acute biopsy features associated with the donor kidney can provide prognostic
      information, in addition to the chronic lesions? This single-center study aimed to evaluate
      which acute and chronic histological lesions and composite histological scores in donor
      kidney intraoperative biopsies alone or in combination with clinical variables are best
      associated with short- and long-term kidney graft outcomes, such as impairment of early
      kidney allograft function, immunological acute kidney allograft rejection, pyelonephritis,
      allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years, and graft survival at 1 and 5
      years.
    

Detailed description: 
      130 consecutive patients with end-stage renal disease (ESRD), receiving a kidney only
      transplant from April 2005 to December 2010 in a single center, and having both
      intraoperative biopsies with ≥ 7 glomeruli and ≥ 1 arteries and complete follow-up data up to
      5 years were included in the study.

      Intraoperative biopsy consisted of preimplant biopsy (at the backtable, 1 core) and
      30-minutes postreperfusion biopsy (1 core), which were taken in order to study the impact of
      ischemia/reperfusion injury on transplant outcomes and to serve a reference for subsequent
      biopsies.

      Donor population included live donors (32.6%), ideal deceased donors (50%), expanded-criteria
      donors (7.9%) and 9.0% of non-heart-beating donors. Donors were subjected to donor evaluation
      protocol in accordance with local guidelines, including a standard clinical, instrumental and
      laboratory examination.

      All recipients and donors were Caucasians.

      Histological scoring Needle (14-18-gauge) biopsies were obtained and tissue was fixed in 10%
      buffered formalin and embedded in paraffin. A 3-4 µm sections of preimplant and
      postreperfusion kidney allograft implantation biopsies (KALIMBO) were stained for light
      microscopy with hematoxylin-eosin (3 slides), periodic acid-Schiff (3 slides), and Masson's
      trichrome (1 slide). A minimum of 21 tissue sections were examined for each biopsy.
      Banff-1997 criteria for posttransplant biopsies, Banff-2016 criteria for preimplant biopsies,
      as well as criteria suggested by Remuzzi et al. (1999) and Cosyns et al. (1998) were applied
      for scoring.

      Based on the estimation of individual acute and chronic lesions, the acute, chronic and total
      posttransplant and preimplant Banff scores, Remuzzi score, and acute, chronic and total
      lesion indexes by Cosyns were calculated. In addition, previously published composite
      histological scores, such as chronic allograft damage index (CADI), donor damage score (DDS),
      chronic damage score (CDS), and interstitial fibrosis and fibrous thickening score (CIV) were
      computed.

      Clinical risk factors and outcomes examined The analysis was performed 60 months later after
      the last transplant in the study population. Donor, graft and recipient characteristics and
      transplant outcomes were extracted from archival patient records and outpatient cards blinded
      to all pathologic data. Data were retrieved on donor source, sex and age, and cause of death,
      donation after cardiac death or expanded criteria donation for deceased donors.

      Recipient's pretransplant variables included: age, gender, cause of ESRD, body mass index
      (BMI), dialysis modality and duration, previous transplants, and presence of chronic arterial
      hypertension, defined as a regular intake of antihypertensive drugs. The information related
      to transplantation (cold ischemia time and second warm ischemia time) was also obtained.
      Posttransplant data retrieved were limited to initial graft function (immediate, delayed or
      slow), and the number and time of occurrence of acute rejection episodes or pyelonephritis,
      and time of graft failure defined as return to dialysis therapy.

      All recipients received triple maintenance immunosuppressive therapy consisting of
      calcineurin-inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroid. Each
      patient, enrolled in this study, was followed for five years until death/return to dialysis
      or until December 2015.

      The end points of the study were impairment of early kidney allograft function, immunological
      acute kidney allograft rejection, pyelonephritis, allograft function at 1, 3, 6, 12 months,
      2, 3, 4 and 5 years, and graft survival at 1 and 5 years.
    

Intervention name(s): Intraoperative kidney allograft preimplantation biopsy; Intraoperative kidney allograft postreperfusion biopsy
Intervention type(s): Procedure
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        All recipients and donors were Caucasians and Ukrainians.
      
Biospecimen description: 
      Formalin-fixed paraplast-embedded kidney biopsies were retained in a biorepository.
    
Keywords: kidney transplantation; implantation biopsy; histology; allograft function; allograft survival