Long-term follow-up of the DeKAF cross-sectional cohort study

Abstract

The DeKAF study was developed to better understand the causes of late allograft loss. Preliminary findings from the DeKAF cross‐sectional cohort (with follow‐up < 20 months) have been published. Herein, we present long‐term outcomes in those recipients (mean follow‐up ± SD, 6.6 ± 0.7 years). Eligibility included being transplanted prior to October 1, 2005; serum creatinine ≤ 2.0 mg/dL on January 1, 2006; and subsequently developing new‐onset graft dysfunction leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Histologic findings and DSA were studied in relation to postbiopsy outcomes. Long‐term follow‐up confirms and expands the preliminary results of each of 3 studies: (1) increasing inflammation in area of atrophy (irrespective of inflammation in nonscarred areas [Banff i]) was associated with increasingly worse postbiopsy death‐censored graft survival; (2) hierarchical analysis based on Banff scores defined clusters (entities) that differed in long‐term death‐censored graft survival; and (3) C4d−/DSA− recipients had significantly better (and C4d+/DSA+ worse) death‐censored graft survival than other groups. C4d+/DSA‐ and C4d−/DSA+ had similar intermediate death‐censored graft survival. Clinical and histologic findings at the time of new‐onset graft dysfunction define high‐ vs low‐risk groups for long‐term death‐censored graft survival, even years posttransplant. These findings can help differentiate groups for potential intervention studies.

Donor/Recipient HLA Molecular Mismatch Scores Predict Primary Humoral and Cellular Alloimmunity in Kidney Transplantation

“…Primary humoral alloimmune activation through dnDSA production is a well-characterized deleterious factor inducing chronic ABMR and accelerated graft loss ( 1 , 2 ) and recent reports have recently shown that it may be predicted by quantifying the donor/recipient HLA MM at the molecular level ( 6 , 31 ). However, for B-cell activation in absence of preformed immune memory, cognate T-cell help is required thus, previous de novo T-cell alloimmune priming (dnDST) against donor antigens might also occur, subsequently driving anti-donor humoral immune activation.…”

“…Long-lasting survival of kidney transplantation is greatly challenged by both preformed and primary donor-specific humoral alloimmunity: the former preventing access to transplantation in sensitized patients, and the latter accelerating chronic rejection and premature graft loss ( 1 , 2 ). Between 5 and 9% of kidney transplant recipients may develop de novo donor-specific antibodies (dnDSA) each year mainly against class-II human leukocyte antigens (HLA) ( 3 , 4 ).…”

Inflammation in areas of fibrosis: The DeKAF prospective cohort

“…Histologic analysis of the "index biopsy" has been described in detail. [13][14][15][16] Representative histologic sections were submitted to a central laboratory for analysis; biopsy specimens were interpreted without knowledge of the clinical diagnoses or C4d positivity, by the same pathologist (JG), using the Banff' 97 classification. 2 Scoring of peritubular capillary infiltrates was done as per the Banff 2005 classification.…”

“…(3) i-IFTA continued to be associated with DC-GS after adjusting for Banff "i" score, 13,14 serum creatinine at the time of biopsy, interstitial fibrosis (ci), tubular atrophy (ct), C4d staining, and the presence of donor specific antibody (DSA). In this report, we analyze the impact of i-IFTA and t-IFTA on outcomes in the DeKAF prospective cohort, a much larger population than the C-S cohort and with outcomes available from the time of transplant.…”

Impact of Subclinical Borderline Inflammation on Kidney Transplant Outcomes

“…However, the decision to biopsy is usually based on noninvasive estimates of allograft function that lack sensitivity, 6 and often detect established phenotypes of late acute rejection that are difficult to treat and hasten allograft failure. 7 , 8 …”