Long-term Impact of Subclinical Inflammation Diagnosed by Protocol Biopsy One Year After Renal Transplantation

Thierry, Antoine; Thervet, Éric; Vuiblet, Vincent; Goujon, Jean-Michel; Machet, Marie‐Christine; Nôël, Laure-Hélène; Rioux‐Leclercq, Nathalie; Comoz, F.; Cordonnier, C.; Audigier, François; Marcellin, Luc; Girardot-Seguin, S.; Touchard, Guy

doi:10.1111/j.1600-6143.2011.03695.x

Cited by 54 publications

(49 citation statements)

References 25 publications

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“…This high rate of SCR in the absence of clinical signs underlines the importance and the significance to perform TSB. SCR were equal often observed in CyA and Tac regimens and highest in the rapamycin group as already shown by others (11). But our study was not designed to show differences between different immunosuppressive regimens so data should not be overinterpreted.…”

Section: Discussionsupporting

confidence: 74%

Repeat True Surveillance Biopsies in Kidney Transplantation

et al. 2012

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Section: Discussionsupporting

confidence: 74%

Repeat True Surveillance Biopsies in Kidney Transplantation

et al. 2012

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“…7,15,16 In addition, early protocol subclinical acute rejection findings were shown to have lower eGFR and were linked to increased risk of graft loss at 5 years. 3,8 In contrast, our study did not show an association between early protocol biopsy SAR+IF/TA and long-term graft function, likely because evidence favors treating SAR+IF/TA when diagnosed early after transplant. Early protocol biopsy and treatment of subclinical acute rejection before occurrence of renal dysfunction have been shown to improve renal allograft function and lead to Abbreviations: 95% CI, 95% confidence interval; eGFR, estimated glomerular filtration rate Shown are all clinically relevant variables found to be significant in the univariate analysis at 10% level of significance and selected as a final model retaining as many variables as possible using the Akaike Information Criterion.…”

Section: Discussioncontrasting

confidence: 55%

“…Early protocol biopsy and treatment of subclinical acute rejection before occurrence of renal dysfunction have been shown to improve renal allograft function and lead to Abbreviations: 95% CI, 95% confidence interval; eGFR, estimated glomerular filtration rate Shown are all clinically relevant variables found to be significant in the univariate analysis at 10% level of significance and selected as a final model retaining as many variables as possible using the Akaike Information Criterion. Biopsies were classified as normal ( 3,12,19 There is also a paucity of literature on late protocol biopsies performed after 12 months in kidney transplant recipients, and our study fills the scarcity of knowledge in this area with our findings that late protocol SAR+IF/TA is significantly associated with rate of eGFR decline over long-term follow-up. Other studies have shown that interstitial fibrosis alone in early protocol biopsy may not predict graft functional decline in allografts with good baseline function; however, ongoing inflammation with interstitial fibrosis leads to graft functional decline, 9 which was also shown in our study where there was increasing percentage of recipients with fibrosis in the inflammation groups in late protocol biopsy and thus the presence of progressive fibrosis in inflamed kidneys predicted graft function.…”

Section: Discussionmentioning

confidence: 44%

“…It has been suggested that subclinical acute rejection found on 1-year posttransplant protocol biopsy is predictive of long-term graft survival, 3,4 but there are other studies with contradictory results. 5 Stegall and associates demonstrated that mild fibrosis present at 1 year progressed to more severe forms at 5 years in only 23% of allografts, 6 thereby contradicting assertions by Nankivell and colleagues that chronic allograft nephropathy was a continuum of events whereby tubulointerstitial and glomerular damage, once established, are irreversible, resulting in declining renal function and graft failure.…”

Section: Introductionmentioning

confidence: 98%

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Zachariah

Dwivedi²,

Yip³

et al. 2018

Exp Clin Transplant

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Objectives: Prognostic implications of early protocol biopsies have been studied; however, the value of late protocol biopsy in predicting graft outcome has not been well defined. Here, we compared the effects of early and late protocol biopsy histologic findings in stable kidney allografts and aimed to understand the significance of "borderline" rejection on allograft function. Materials and Methods: We studied 261 biopsies from 159 renal transplant recipients who were on a steroidfree, calcineurin inhibitor and mycophenolate mofetil regimen and who received transplants between 2004 and 2012 with mean follow-up of 5 years. Early (between 3 and 9 mo) and subsequent late (between 12 and 24 mo) protocol biopsies were performed. Biopsies were classified as normal, interstitial fibrosis and/or tubular atrophy, subclinical acute rejection with interstitial fibrosis and/or tubular atrophy, and borderline rejection with interstitial fibrosis and/or tubular atrophy. A linear mixed-effects model was used to determine the effects of early and late protocol biopsies on estimated glomerular filtration rate changes, with baseline time for estimated glomerular filtration rate fixed at 12 months. Results: The adjusted model showed that estimated glomerular filtration rate at 3 months, donor age, delayed graft function, and early protocol biopsies were associated with baseline estimated glomerular filtration rate at 12 months. Estimated glomerular filtration rate changes over time were associated with findings of interstitial fibrosis and/or tubular atrophy at early biopsy and subclinical acute rejection and borderline rejection at late biopsy. At last follow-up, final estimated glomerular filtration rate was significantly associated with interstitial fibrosis and/or tubular atrophy at early biopsy and with subclinical acute rejection at late biopsy. Conclusions: Although early protocol biopsy predicted baseline estimated glomerular filtration rate, late biopsy was important for predicting changes in function over time. In addition, a diagnosis of "borderline" rejection on protocol biopsies predicted long-term graft function.

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“…10 Other authors have suggested the use of biopsies to detect subclinical rejection. 11,12 A total of 61 biopsies were analyzed and the following oxidative stress enzymes were detected by Western blot: catalase (60 kilodaltons), MnSoD (25 kilodaltons), CuZnSoD (23 kilodaltons), thioredoxin reductase (55 kilodaltons), thioredoxin (2b1) (12 kilodaltons), and thioredoxin (62 kilodaltons).…”

Section: Discussionmentioning

confidence: 99%

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2015

Exp Clin Transplant

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Objectives: Kidney allograft biopsies are performed after kidney transplant to determine graft dysfunction. We aimed to define and measure the oxidative stress occurring in these biopsies and compared these biopsies with donor pretransplant biopsies. Materials and Methods: The biopsy procedure was done according to the unit protocol. A core of tissue was taken for research purposes only when it was safe enough to proceed for an extra core. Common indications for biopsy were acute or chronic graft dysfunction, delayed graft function, acute cellular rejection, and calcineurin toxicity. There were 17 pretransplant biopsies taken from deceased-donor kidneys. Biopsy specimens were snap frozen immediately in liquid nitrogen and stored at -70°C. Samples were processed for Western blot and tested for markers of oxidative stress. Results: There were 61 biopsies analyzed. Oxidative stress enzymes were evaluated by Western blot including catalase, manganese superoxide dismutase, copper zinc superoxide dismutase, thioredoxin reductase, and thioredoxin. Upregulation of most antioxidant enzymes was observed in pretransplant biopsies. Increased expression of manganese superoxide dismutase was observed in donor kidneys and kidneys with acute cellular rejection and calcineurin toxicity. Copper zinc superoxide dismutase and catalase were elevated in donor and acute cellular rejection biopsies. Thioredoxin was elevated in donor biopsies and thioredoxin reductases were elevated in donor biopsies and biopsies with acute cellular rejection and calcineurin toxicity. Conclusions:The kidney allograft biopsies showed that oxidative stress levels were elevated during allograft dysfunction in all biopsies regardless of diagnosis, but not significantly. The levels also were elevated in pretransplant biopsies. The study showed that oxidative stress is involved in various acute injuries occurring within the allograft.

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Long-term Impact of Subclinical Inflammation Diagnosed by Protocol Biopsy One Year After Renal Transplantation

Cited by 54 publications

References 25 publications

Repeat True Surveillance Biopsies in Kidney Transplantation

Repeat True Surveillance Biopsies in Kidney Transplantation

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