Tumor Necrosis Factor α Blockade to Ameliorate Renal ischemia Reperfusion Injury

Moers, Cyril; Pol, Robert A.; Borst, Martin H. de

doi:10.1097/tp.0000000000001221

Cited by 2 publications

(2 citation statements)

References 10 publications

(7 reference statements)

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“…[12][13][14] On this basis, TNF-α inhibitors have therefore been proposed for use in kidney transplant recipients to improve outcome. 15 Here, we used human genetics to probe whether targeting TNF-α in renal transplantation will provide clinical benefit. Studies of human genetics are powerful tools in validating therapeutic targets because genetically-backed drug targets are reported to be twice as likely to lead to approved therapeutics compared to traditional drug discovery targets.…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes

Poppelaars

Costa

Faria

et al. 2021

Preprint

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Introduction Kidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-alpha) gene (TNF) polymorphisms on kidney graft survival. Methods We performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function (PNF) and death-censored kidney allograft survival in 1,271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands. Results The G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of PNF (odds ratio: 2.05; 95%-CI: 1.06-3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P<0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05-2.19, P = 0.028). Conclusion Kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-alpha blockade in improving kidney transplantation outcomes.

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Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes

Poppelaars

Costa

Faria

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“… 12–14 On this basis, TNF-α inhibitors have therefore been proposed for use in kidney transplant recipients to improve outcome. 15 …”

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes

Poppelaars¹,

Costa²,

Faria³

et al. 2022

JIR

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Introduction Kidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved over the past two decades. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for kidney transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene ( TNF ) polymorphisms on kidney graft survival after transplantation. Methods We performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function and death-censored kidney allograft survival in 1271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands. Results The G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of immediate graft loss (odds ratio: 2.05; 95%-CI: 1.06–3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival ( P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05–2.19, P = 0.028). Discussion In conclusion, kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.

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Tumor Necrosis Factor α Blockade to Ameliorate Renal ischemia Reperfusion Injury

Cited by 2 publications

References 10 publications

Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes

Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes

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