Pre‐transplant end‐stage renal disease‐related immune risk profile in kidney transplant recipients predicts post‐transplant infections

Crépin, Thomas; Gaiffe, Émilie; Courivaud, Cécile; Roubiou, Caroline; Laheurte, Caroline; Moulin, Anne‐Marie; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Dürrbach, Antoine; Heng, Anne-Élisabeth; Saas, Philippe; Bamoulid, Jamal; Ducloux, Didier

doi:10.1111/tid.12534

Cited by 31 publications

(26 citation statements)

References 18 publications

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“…However, we observed more frequent opportunistic infections in ATG-treated patients. This result con rms preliminary analyses performed earlier in this study (17). Overall, ATG is not associated with a substantial increase in early infectious complications except for opportunistic infections.…”

Section: Discussionsupporting

confidence: 91%

Impact of polyclonal antithymocyte globulins on kidney transplant outcomes in real-life: a propensity score analysis

Bamoulid

Crépin

Gaiffe

et al. 2020

Preprint

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Background: Randomized studies reported a marginal superiority of polyclonal antithymocyte globulins (ATG, Thymoglobulin®, Sanofi, Gentilly, France, or Fresenius®, Bad Homburg, Germany) to prevent acute rejection compared to monoclonal anti-CD25 antibodies (IL2Ra). Nevertheless, the representativeness and the generalizability of these studies are questionable. Methods: We studied the impact of ATG use in real-life conditions in a multicenter study. Propensity score analysis was performed to address potential confounding by indication. Results: 817 patients were included. Logistic regression revealed that age, male gender, a pre-transplant history of cancer, presence of anti-HLA antibodies, previous kidney transplantation, and transplant center were associated with ATG use. The area under the curve of the propensity score was 0.84 + 0.02. ATG use was not associated with a lower rate of acute rejection (18.2% in ATG-treated patients vs 15.8% in non-ATG-treated patients, p =0.356). Adjustment for propensity score slightly modified the relationship between ATG and acute rejection towards a more neutral effect ( p =0.913). Score match analysis recapitulated the previous result. ATG use was associated with the occurrence of opportunistic infection ( p =0.034). There was no difference in graft loss or death between the two groups. Conclusions: In real-life conditions, ATG does not substantially reduce the risk of acute rejection after kidney transplantation. A better discrimination of patients who may benefit from ATG is required.

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Section: Discussionsupporting

confidence: 91%

Impact of polyclonal antithymocyte globulins on kidney transplant outcomes in real-life: a propensity score analysis

Bamoulid

Crépin

Gaiffe

et al. 2020

Preprint

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“…However, previous studies suggest pre-transplant TEMRA frequency may mitigate the risk of post-transplant infections. Indeed, we previously reported that immune risk profile is associated with post-transplant infectious outcomes [ 38 ]. The absence of association may result from confounding parameters (including short duration of follow-up, consideration of different kinds of infections, immunosuppressive drugs, …) or alternatively from a differential impact of TEMRA on allo-immune and anti-infectious responses.…”

Section: Discussionmentioning

confidence: 99%

ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications

et al. 2018

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BackgroundEnd-stage renal disease (ESRD) causes premature ageing of the immune system. However, it is not known whether hemodialysis (HD) and peritoneal dialysis (PD) similarly affect the T cell system.MethodsThe aim of our study was to analyse whether dialysis modality may mitigate ESRD-induced immune senescence. We explored a large population of patients (675 ESRD patients) and both confirmed and refined the results in a second cohort (84 patients).ResultsHD patients exhibited higher inflammatory monocytes counts (44/mm3 (1–520) vs 36/mm3 (1–161); p = 0.005). Patients on HD also had higher frequency of CD8 T cells (24% (7–61) vs 22% (8–42); p = 0.003) and reduced CD4/CD8 ratio. Such results were confirmed in the second cohort. Moreover, both CD4 + CD57 + CD28- (3.25% (0–38.2) vs 1.05% (0–28.5); p = 0.068) and CD8 + CD57 + CD28- (38.5% (3.6–76.8) vs 26.1 (2.1–46.9); p = 0.039) T cells frequencies were increased in HD patients. Telomere length did not differ according to dialysis modality, but was inversely related to ferritin levels (r = − 0.33; p = 0.003). There was a trend towards higher telomerase activity in PD patients (11 ± 13 vs 6 ± 11; p = 0.053). Thymic function was not different in PD and HD patients. Patients on PD before transplantation had a higher risk of acute rejection after kidney transplantation (HR, 1.61; 95%CI, 1.02 to 2.56; p = 0.041).ConclusionsMore pronounced inflammation with hemodialysis may induce premature aging of the immune system. This observation correlates with a lower risk of acute kidney rejection in patients previously on HD. Clinical consequences in patients maintained on dialysis should be determined.Trial registrationTrial registration: NCT02843867, registered July 8, 2016.

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“…There are several studies that have examined the use of a composite immune score in SOT recipients but these are difficult to compare directly with ours . The majority of these studies have been performed in the early post‐transplant period, whereas our study specifically examined patients who were stable on immunosuppression and some months or years post‐transplant (median time from transplant 4.1 years).…”

Section: Discussionmentioning

confidence: 99%

“…32 There are several studies that have examined the use of a composite immune score in SOT recipients but these are difficult to compare directly with ours. [13][14][15]23,26 The majority of these studies have diction models. Importantly, we did not simultaneously examine rates of rejection which would be necessary in any study looking to reduce immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

A simple score can identify kidney transplant recipients at high risk of severe infection over the following 2 years

Dendle

Polkinghorne

Mulley

et al. 2019

Transplant Infectious Dis

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Background The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. Methods We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. Results Fifty‐nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67‐0.83). Conclusion Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high‐risk patients. This data can inform research that examines strategies to reduce the risks of infection.

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Pre‐transplant end‐stage renal disease‐related immune risk profile in kidney transplant recipients predicts post‐transplant infections

Abstract: Pre-transplant IRP is associated with an increased risk of post-transplant infection.

Cited by 31 publications

References 18 publications

Impact of polyclonal antithymocyte globulins on kidney transplant outcomes in real-life: a propensity score analysis

Impact of polyclonal antithymocyte globulins on kidney transplant outcomes in real-life: a propensity score analysis

ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications

A simple score can identify kidney transplant recipients at high risk of severe infection over the following 2 years

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