Kidney Allograft Survival After Acute Rejection, the Value of Follow-Up Biopsies

Ters, Mireille El; Grande, Joseph P.; Keddis, Mira T.; Rodrigo, Emilio; Chopra, Bhavna; Dean, Patrick G.; Stegall, Mark D.; Cosio, Fernando G.

doi:10.1111/ajt.12370

Cited by 161 publications

(139 citation statements)

References 35 publications

(47 reference statements)

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“…Although, not now a common cause of direct and immediate graft failure, cellular rejection remains a potent and relevant risk factor for subsequent graft failure (15)(16)(17), thereby highlighting the relevance of the current findings to contemporary transplantation. Unsurprisingly, no association between transitional B cells and ABMR was seen, as these rejection episodes were driven by nonadherence rather than a predisposing immune profile.…”

Section: Discussionmentioning

confidence: 67%

Transitional B Lymphocytes Are Associated With Protection From Kidney Allograft Rejection: A Prospective Study

Shabir

Girdlestone

Briggs

et al. 2015

American Journal of Transplantation

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Recent cross‐sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody‐mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation. When modeled as a time‐dependent covariate, transitional B cell frequencies (but not total B cells or “regulatory” T cells) were associated with protection from acute rejection (any Banff grade; HR: 0.60; 95% CI: 0.37–0.95; p = 0.03). No association between transitional B cell proportions and either de novo donor‐specific or nondonor‐specific antibody (dnDSA; dnNDSA) formation was evident, although preserved transitional B cell proportions were associated with reduced rejection rates in those patients developing dnDSA. Three episodes of ABMR occurred, all in the context of nonadherence, and all associated with in vitro anti‐HLA T cell responses in an ELISPOT assay (p = 0.008 versus antibody‐positive patients not experiencing ABMR). This prospective study supports the potential relevance of transitional (“regulatory”) B cells as a biomarker and therapeutic intervention in transplantation, and highlights relationships between humoral immunity, cellular immunity and nonadherence.

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Section: Discussionmentioning

confidence: 67%

Transitional B Lymphocytes Are Associated With Protection From Kidney Allograft Rejection: A Prospective Study

Shabir

Girdlestone

Briggs

et al. 2015

American Journal of Transplantation

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“…Donor-reactive T cells and anti-HLA antibodies are established mediators of transplant injury and must be controlled by appropriate immunosuppression. Inadequate immunosuppression predisposes to acute cellular rejection and antidonor HLA alloantibody formation, both of which are associated with progressive interstitial fibrosis and tubular atrophy (IF/TA) and shortened graft survival (4)(5)(6). In contrast, excessive immunosuppression not only predisposes to infectious complications, but is associated with multiple toxicities including direct kidney damage (7) and indirect effects of drug-induced diabetes (8) and hypertension (9).…”

Section: Introductionmentioning

confidence: 99%

Complement as a multifaceted modulator of kidney transplant injury

Cravedi¹,

Heeger²

2014

J. Clin. Invest.

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“…[4][5][6][7] Isolated endarteritis of kidney transplants is a newly reported and increasingly recognized entity. 8 Cohort studies identified patients whose transplanted kidneys stopped working effectively in association with isolated endarteritis.…”

mentioning

confidence: 99%

Isolated Endarteritis and Kidney Transplant Survival

Sis

Bagnasco²,

Cornell

et al. 2015

Journal of the American Society of Nephrology

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Isolated endarteritis of kidney transplants is increasingly recognized. Notably, microarray studies revealed absence of immunologic signatures of rejection in most isolated endarteritis biopsy samples. We investigated if isolated endarteritis responds to rejection treatment and affects kidney transplant survival. We retrospectively enrolled recipients of kidney transplant who underwent biopsies between 1999 and 2011 at seven American and Canadian centers. Exclusion criteria were recipients were blood group-incompatible or crossmatch-positive or had C4d-positive biopsy samples. After biopsy confirmation, patients were divided into three groups: isolated endarteritis (n=103), positive controls (type I acute T cell-mediated rejection with endarteritis; n=101), and negative controls (no diagnostic rejection; n=103). Primary end points were improved kidney function after rejection treatment and transplant failure. Mean decrease in serum creatinine from biopsy to 1 month after rejection treatment was 132.6 mmol/L (95% confidence interval [95% CI], 78.7 to 186.5) in patients with isolated endarteritis, 96.4 mmol/L (95% CI, 48.6 to 143.2) in positive controls (P=0.32), and 18.6 mmol/L (95% CI, 1.8 to 35.4) in untreated negative controls (P,0.001). Functional improvement after rejection treatment occurred in 80% of patients with isolated endarteritis and 81% of positive controls (P=0.72). Over the median 3.2-year followup period, kidney transplant survival rates were 79% in patients with isolated endarteritis, 79% in positive controls, and 91% in negative controls (P=0.01). In multivariate analysis, isolated endarteritis was associated with an adjusted 3.51-fold (95% CI, 1.16 to 10.67; P=0.03) risk for transplant failure. These data indicate that isolated endarteritis is an independent risk factor for kidney transplant failure.

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Kidney Allograft Survival After Acute Rejection, the Value of Follow-Up Biopsies

Cited by 161 publications

References 35 publications

Transitional B Lymphocytes Are Associated With Protection From Kidney Allograft Rejection: A Prospective Study

Transitional B Lymphocytes Are Associated With Protection From Kidney Allograft Rejection: A Prospective Study

Complement as a multifaceted modulator of kidney transplant injury

Isolated Endarteritis and Kidney Transplant Survival

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