Contribution of donor age and ischemic injury in chronic renal allograft dysfunction

Tullius, Stefan G.; Reutzel‐Selke, Anja; Nieminen-Kelhä, Melina; Jonas, Sven; Egermann, F; Heinzelmann, T.; Bechstein, Wolf O.; Volk, H D

doi:10.1016/s0041-1345(98)02004-1

Cited by 48 publications

(53 citation statements)

References 3 publications

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“…Unlike studies of the allogeneic factor, 12,14,22 studies evaluating CI in renal transplant models [23][24][25] have only occasionally assessed its longterm consequences. 21,26 Moreover, as in these studies serum creatinine levels are rarely considered we can only compare our results with those reported in Kouwenhoven and colleagues, 26 in which serum creatinine levels were reported as being consistently stable up to week 24. We cannot rule out the possibility that this late renal dysfunction might be related to the concurrence of cyclosporin and ischemia because cyclosporin blood levels were For interstitial area, silver methenamine-stained slices were evaluated with light microscopy and quantified by the morphometric point-counting method at ϫ200 in at least five fields per kidney and expressed as a percentage (%).…”

Section: Discussionmentioning

confidence: 68%

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

Herrero‐Fresneda

Torrás

Condom

et al. 2003

The American Journal of Pathology

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This study assesses the individual contributions of the nonalloreactive factor, cold ischemia (CI), and alloreactivity to late functional and structural renal graft changes, and examines the effect of the association of both factors on the progression of chronic allograft nephropathy. Lewis rats acted as receptors of kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5 hours. The rats were divided into four groups: Syn, syngeneic graft; SynI, syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI. Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histological damage at 24 weeks. Only when CI and allogenicity were combined did immediate posttransplant mortality occur, while survivors showed accelerated renal insufficiency that induced further mortality at 12 weeks after transplant. Solely ischemic rats developed renal insufficiency. Renal structural damage in ischemic rats was clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis appeared only in the allogeneic groups. There was increased infiltration of macrophages and expression of mRNA-transforming growth factor-␤1 in the ischemic groups, irrespective of the allogeneic background. The joint association of CI plus allogenicity significantly increased cellular infiltration at both early and late stages, aggravating tubulointerstitial and vascular damage considerably. In summary, CI is mainly responsible for tubulointerstitial damage, whereas allogenicity leads to vascular lesion. Chronic allograft nephropathy (CAN) is a multifactorial process that leads to late allograft loss in renal transplantation and is caused by both alloreactive and nonalloreactive factors.

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Section: Discussionmentioning

confidence: 68%

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

Herrero‐Fresneda

Torrás

Condom

et al. 2003

The American Journal of Pathology

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“…The present model, using one the most attractive species for the future, could be crucial in under- standing the complex interrelationship between IRI and graft dysfunction. A recent study has also demonstrated that cold ischemic trauma exerted a permanent detrimental effect on the graft (Tullius et al, 2000).…”

Section: Discussionmentioning

confidence: 95%

Polyethylene Glycol Reduces Early and Long-Term Cold Ischemia-Reperfusion and Renal Medulla Injury

Fauré¹,

Hauet²,

Han³

et al. 2002

J Pharmacol Exp Ther

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Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30 -40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4 ϩ , PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.

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“…Despite this established clinical phenotype, there is little experimental evidence that provides mechanistic insights into how aging within the donor enhances the development of allograft vasculopathy. A prior study in a rat kidney allograft model found that donor age (up to 18 months) synergized with donor ischemia time (up to 120 minutes) in impairing allograft function (defined as creatinine clearance and proteinuria) (57). However, other components of the allograft have not yet been examined as contributors of increased vascuwhich increases antidonor immunity (30).…”

Section: Impact Of Aging On the Donormentioning

confidence: 99%

Aging and the immune response to organ transplantation

Colvin¹,

Smith²,

Tullius³

et al. 2017

Journal of Clinical Investigation

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Contribution of donor age and ischemic injury in chronic renal allograft dysfunction

Cited by 48 publications

References 3 publications

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

Polyethylene Glycol Reduces Early and Long-Term Cold Ischemia-Reperfusion and Renal Medulla Injury

Aging and the immune response to organ transplantation

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